BSAC AntimicrobialStewardship FromPrinciplestoPractice Ebook

E-BOOK
E-BOOK
E-BOOK
ANTIMICROBIAL
STEWARDSHIP
FROM PRINCIPLES
TO PRACTICE
THIS E-BOOK HAS BEEN
DEVELOPED BY BSAC
IN COLLABORATION
WITH ESGAP/ESCMID
PLEASE NOTE THAT THE AUTHORS' CHAPTERS DO NOT REFLECT THE OPINION
OF ANY ORGANISATIONS THEY MAY BE ALIGNED WITH
GLOSSARY OF TERMS
ACKNOWLEDGEMENT
No venture into creating such an ambitious project can be done without support of a good team. It has been said
"a team is not a group of people who work together but rather a group of people who trust each other ".
Our team epitomises this. With that in mind on behalf of all the editors and the contributors I would like to acknowledge
the diligent, persistent and patient support of BSAC colleagues – Tracey Guise, CEO; Sally Bradley, eLearning manager
and Neil Watson without whom the transformation of the written word into a visually engaging eBook could not
have been accomplished. Thank you all.
BSAC is grateful to the following companies who provided, as part of a consortia sponsorship pool, unrestricted grants
to support the cost of developing this e-book: Alere now Abbott, Accelerate Diagnostics, MSD, Pfizer Inc
SPONSOR STATEMENTS
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CONTENTS
PREFACE 10 CHAPTER 2 - ANTIBIOTIC 27
USE AND MISUSE ACROSS
CHAPTER 1 - 12 THE RANGE OF HEALTHCARE
OVERVIEW OF AMR COMMUNITIES AND THE
DRIVERS/DETERMINANTS
Define antimicrobial and antibiotic resistance OF MISUSE
in the human population ....................................................... 13
Antibiotic consumption and prevalence
What is antimicrobial resistance? ........................................ 13 of use-in primary and secondary care ............................... 27
What is the difference between antibiotic Global consumption of antibiotics ..................................... 28
and antimicrobial resistance? ............................................... 13
Antibiotic use in the community setting ........................... 29
Antibiotic resistance is a natural and
acquired problem .................................................................... 13 Antibiotic use in the hospital setting .................................. 31
How do antibiotics work? ...................................................... 14 Long term care ....................................................................... 34
Where does resistance occur and how Misuse of antibiotics .............................................................. 35

does resistance happen? ...................................................... 15
Non-prescription use of antibiotics .................................... 37
What are the drivers for resistance and potential
Determinants of antibiotic prescribing and use .............. 37
approaches to tackle resistance? ........................................ 15
What are the drivers for the use and

misuse of antibiotics? ............................................................. 17
CHAPTER 3 - WHAT IS 40
ANTIMICROBIAL
The global epidemiology of antibiotic
resistance and consumption in humans ............................ 19 STEWARDSHIP?
What are the clinical and economic impact What is Antimicrobial Stewardship
of drug resistant infections and impact and why is it Important? ....................................................... 40
on health care acquired infections? .................................... 19
Impact of Antimicrobial Stewardship
What is the economic impact of AMR? .............................. 21 (AMS) programs ....................................................................... 41
Stewardship as a solution to Combat AMR ...................... 23 Key principles of prudent

antimicrobial prescribing ...................................................... 42
What is antimicrobial stewardship and
what are its goals? ................................................................. 24 Antimicrobial Stewardship Goals:
Improve Patient Outcomes .................................................. 43
How does this look in practice? .......................................... 26
LEARNING OUTCOME:
Reduce collateral damage ................................................... 43
Reduce antibiotic consumption CHAPTER 6 - EXPERTISE, 67
and costs without increasing mortality
or infection-related re-admissions ..................................... 46 STRUCTURES AND
Optimise healthcare costs ................................................... 46
ORGANISATION
LEARNING OUTCOME: Evaluate core Defining your organisation
elements of antimicrobial stewardship and healthcare sector ........................................................... 67
and discuss opportunities to implement Situating antimicrobial stewardship
core elements in your practice setting .............................. 47 within the organisation ......................................................... 68
LEARNING OUTCOME: Patient Cases: National action plans ............................................................ 70
Apply key principles of prudent
antimicronial prescribing to the Examining workforce engagement
following scenarios ................................................................ 47 across professional groups ................................................. 70
Towards integrated models of ams .................................... 70

CHAPTER 4 - KEY STEPS 49
IN DEVELOPING AN CHAPTER 7 - THE ROLE 72
ANTIMICROBIAL STEWARDSHIP OF LABORATORY AND RAPID
PROGRAMME DIAGNOSTICS/BIO-MARKERS
Introduction ............................................................................. 49 IN STEWARDSHIP
Business case .......................................................................... 51 Introduction to empirical prescribing ................................ 72
Antimicrobial stewardship committee ................................ 51 The use of currently available diagnostic

tests to inform the optimal use of antibiotics .................. 74
Developing antimicrobial prescribing guidelines ........... 55
The role of the laboratory in stewardship ........................ 75
Educate and train ................................................................... 55
Role of the clinician in laboratory testing ......................... 76
CHAPTER 5 - ASSESSING 59 Acute phase proteins and other biomarkers ................... 77
THE NEED AND MOTIVATION
Introduction ............................................................................. 59 CHAPTER 8 - OPTIMISING 78
STEWARDSHIP THROUGH
Resources ................................................................................ 60
BETTER PK-PD
Leadership Structure and Accountability .......................... 61
Pharmacokinetics and
Process ..................................................................................... 62 pharmacodynamics (PK-PD) ................................................ 78
Outcomes ................................................................................ 63
Pharmacodynamic parameters
Motivation ................................................................................ 64 predictive of outcome ........................................................... 79
Conclusion ............................................................................... 64 Commonly used antimicrobial

pharmacodynamic parameters ........................................... 79
Summary of Learning Outcomes ........................................ 66
When is PK/PD clinically relevant? ..................................... 80
Clinical application of PK/PD

in special circumstances ....................................................... 81
Interactive Case study .......................................................... 86

Continuous infusions of CHAPTER 11 - METHODS 119
beta-lactam antibiotics .......................................................... 87
FOR IMPROVING THE QUALITY
Therapeutic Drug monitoring (TDM) .................................. 88 OF ANTIMICROBIAL PRESCRIBING
Combination Therapy ........................................................... 88 USING LOCAL DATA
Resistance suppression ........................................................ 88 Introduction ............................................................................ 119
Getting started with improving

Toxicodynamics ...................................................................... 88
antimicrobial prescribing .................................................... 120
Optimising PK/PD for Quality improvement (QI) approach ................................. 121
Antimicrobial stewardship ................................................... 89
How to get started with improving
antimicrobial prescribing ..................................................... 127
CHAPTER 9 - 91
THE STEWARDSHIP TOOLKIT CHAPTER 12 - 128
How to implement a successful ANTIMICROBIALSTEWARDSHIP
antimicrobial stewardship programme .............................. 91
AND BEHAVIOUR CHANGE
Proposed members of antimicrobial
stewardship groups ............................................................... 93 The need to optimise antibiotic prescribing .................. 128
Position of antimicrobial stewardship The role of behaviour and culture in

groups within the organisation ........................................... 94 antibiotic prescribing .......................................................... 129
How to identify priority areas in Hierarchies ............................................................................ 130

which to focus ASP ................................................................ 95 Behaviour change as quality improvement .................... 131
The ASP toolkit ....................................................................... 96 Examples of successful application
Core interventions ................................................................. 97 of behaviour change theory to
antimicrobial stewardship research ................................. 132
Guideline development ...................................................... 100
Additional Interventions ..................................................... 102 CHAPTER 13 - KNOWLEDGE 133

How do I assess the effectiveness of AND PRACTICE IN
an antimicrobial stewardship programme? .................... 106 STEWARDSHIP: EDUCATIONAL
Communication .................................................................... 108 COMPETENCIES FOR PRUDENT
PRESCRIBING
CHAPTER 10 - WHAT IS 110 Introduction ............................................................................ 133
MEASUREMENT AND WHY
Current landscape: National strategies
IS IT IMPORTANT? to improve AMS knowledge and practice ...................... 134
Quantity of antimicrobial use ............................................. 112 Examples of how countries have
implemented objective 1 of the global
Quality of antimicrobial use ................................................ 114
AMR action plan ................................................................... 136
Using data to improve antimicrobial stewardship ......... 116
Free worldwide access to AMS training .......................... 137
What about data visualisation? ........................................... 117
Summary ................................................................................ 140
What are competences for antimicrobial

prescribing and stewardship ............................................. 140
Who should the competences CHAPTER 16 - 167
be intended for? ................................................................... 140
STEWARDSHIP IN THE
Developing competences ................................................... 141
RESOURCE LIMITED SETTINGS -
Current Landscape: Developed EXAMPLES OF GLOBAL
competences across the world:
UK - National competences ................................................ 141
SUCCESS STORIES
Expert professional curriculum Introduction ........................................................................... 168
for antimicrobial pharmacists in the UK .......................... 142
South Africa ........................................................................... 168
Guidance for the Knowledge and Skills
Global success story: antimicrobial stewardship
Required for Antimicrobial Stewardship
model to reduce excessive prescribing ................ 168
Leaders (USA) ....................................................................... 143
Process measures involving
An Antibiotic Stewardship Curriculum
“low-hanging fruit” for pharmacist
for Medical Students ........................................................... 143
audit during dedicated antibiotic
Europe .................................................................................... 143 rounds (all patients on antibiotics) ......................... 168
Educational Resources ....................................................... 143 AMS “breakthrough series collaborative”

model for implementation and
A GP guide to antimicrobial resistance ........................... 146 monitoring process .................................................... 169
The importance of collaborative learning

CHAPTER 14 - ANTIBIOTIC 148 sessions and standardised measurement .............. 171
STEWARDSHIP EDUCATION The importance of feedback to facilitate
IN LOW RESOURCE SETTINGS adjustments to hospital action plans
following self-monitoring ............................................ 171
Recognising a problem ....................................................... 148
Impact of the AMS model .......................................... 173
The Challenge ...................................................................... 148
India ......................................................................................... 175
Making the most of what is already out there ............... 148
Development of drug resistance ............................. 175
Educating health care professionals in low
resource settings – a hospital-based approach ............ 151 Story 1: Making & Utilisation of an antibiogram:
Bugs vs Drugs .............................................................. 176
CHAPTER 15 - 153 Story 2: Prescription auditing as a concept

and interpretation ........................................................ 177
STEWARDSHIP IN
DEVELOPED COUNTRIES Story 3: Focus group discussions ............................ 178
Other contributory factors ......................................... 179

North america ....................................................................... 153
South America ...................................................................... 180
Europe .................................................................................... 155
Story 1: The problems: inappropriate antibiotic
Gulf cooperation states ...................................................... 158
use and antibiotic resistance in Latin
Australia ................................................................................. 162 American countries .................................................... 180
Story 2: The process and impact of introducing

regulations for antibiotic sales in Chile,
Brazil and Mexico ....................................................... 180
Conclusions ................................................................. 183

CHAPTER 17 - 185 Definition ................................................................................ 213
STEWARDSHIP IN LONG Rationale ................................................................................ 214

TERM CARE FACILITIES Importance ............................................................................ 214
Long term care facility setting factors ............................. 185 Ranking .................................................................................. 214
Antimicrobial prescribing practices .................................. 187 Requirement/Pre requisite to prevent SSI ...................... 215
Impact of Antimicrobial Resistance .................................. 188 Selection of antimicrobial agent

for surgical prophylaxis ...................................................... 215
Surveillance of Healthcare Acquired Infections
and antimicrobial prescribing ............................................ 190 Time of administration ........................................................ 216
Antimicrobial stewardship ................................................. 190 Repeat dosing ........................................................................ 217
Focus on UTI and CAUTI in LTCF ..................................... 192 Duration .................................................................................. 217
Sepsis in LTCF ....................................................................... 195 Topical adminstration of irrigations,

pastes, and washes ............................................................. 218
Antimicrobial Stewardship in LTCFs ................................ 195
Contributory factors in surgical site infection ................ 218
CHAPTER 18 - 197 Summary ................................................................................ 219

STEWARDSHIP IN THE
INTENSIVE CARE UNIT CHAPTER 21 - 220
ANTIFUNGAL STEWARDSHIP
Introduction ............................................................................ 197
introduction .......................................................................... 220
Program Structure ................................................................ 198
Some basic mycology ......................................................... 221
Interventions ........................................................................ 200
What is antifungal stewardship (AFS)? ........................... 222
Outcome Measures ............................................................ 202
Aims of AFS programme ................................................... 222
Summary ............................................................................... 204
What are the benefits of AFS? ......................................... 222
CHAPTER 19 - 205 What are the disadvantages of AFS? ............................. 223
STEWARDSHIP IN THE What are the differences between
IMMUNOCOMPROMISED Antifungal Stewardship and
PATIENT SETTING Antimicrobial Stewardship (AMS)? .................................. 223
Funding of antifungals and its effects on AFS ............. 223

Introduction .......................................................................... 205
Types of antifungal use ...................................................... 224
AMS in the Immunocompromised
Not just antibacterials ......................................................... 207 Diagnosing fungal infections ............................................ 224
Challenges to AMS in the AFS: How do you do it? ..................................................... 225
immunocompromised ........................................................ 208
Examples of AFS that work include ................................ 226
Opportunities for AMS in the
immunocompromised .......................................................... 211 AFS: What are the challenges? ......................................... 227
Summary ................................................................................ 212 Who do you need to involve? ............................................ 227
What do you need? ............................................................ 228

CHAPTER 20 - 213 How do you continue? ....................................................... 229
SURGICAL PROPHYLAXIS
Background ........................................................................... 213
CHAPTER 22 - 230 CHAPTER 25 - THE ROLE 265
STEWARDSHIP IN PAEDIATRICS OF THE NURSE IN
Introduction .......................................................................... 230
STEWARDSHIP
Antibiotic prescribing for children Why should nurses be involved
in community based setting ............................................. 232 in stewardship? .................................................................... 266
Antibiotic prescribing for children Expanding the participation of nurses

in hospital settings ............................................................... 237 in antimicrobial stewardship .............................................. 267
Evaluating the quality of antibiotic Public health and community nursing

prescribing in children ....................................................... 239 contribution to antimicrobial stewardship ..................... 269
Summary ................................................................................ 241 Integration between nursing roles

and activities in AMR and other professionals .............. 270
CHAPTER 23 - 242 Stewardship, a target for nurses

in executive and directive positions ................................ 270
ANTIMICROBIAL
STEWARDSHIP AND OPAT Nurse-focused interventions
in antimicrobial stewardship ............................................... 271
Introduction ........................................................................... 243 Barriers to resolve the participation
Transitions of Care from Acute to of nurses in stewardship .................................................... 273
Post-acute OPAT Care Settings ....................................... 244 Conclusion ............................................................................. 275
OPAT Patient Diversity and Distinct
OPAT Care Models ............................................................. 245
CHAPTER 26 - THE ROLE 277
The Physician Steward and OPAT OF THE PHARMACIST
care in the Underserved .................................................... 246
IN STEWARDSHIP
OPAT-Stewardship Dilemma .............................................. 247
Patient care ........................................................................... 278
Expanded Role of the Stewardship
Pharmacist in OPAT ............................................................ 249 Educator ................................................................................. 279
Conclusion ............................................................................ 250 Research ............................................................................... 280
Rapid Diagnostic Tests ...................................................... 280

CHAPTER 24 - THE USE 253 Drug Therapy Expert ........................................................... 281
OF INFORMATION
Patient Safety ........................................................................ 281
TECHNOLOGY TO SUPPORT
Quality Care ......................................................................... 282
ANTIMICROBIAL STEWARDSHIP
Advocacy .............................................................................. 282
Overview ............................................................................... 253
Using information technology to CHAPTER 27 - 284

support antimicrobial stewardship .................................. 255
INFORMING & INFLUENCING:
Are Antimicrobial CDSSs effective? ................................ 256
STEWARDSHIP, POLITICIANS,
Types of antimicrobial CDSSs .......................................... 256 & THE MEDIA
What are the factors that are likely to result Going public ......................................................................... 285
in successful implementation of a CDSS? ..................... 262
Mainstream media .............................................................. 288
Summary ............................................................................... 263
New media ........................................................................... 288
Politicians .............................................................................. 289

OUTCOMES 294 AUTHORS 325
Chapter 1 ............................................................................... 294 Chapter 1 - Dilip Nathwani ................................................ 325
Chapter 2 .............................................................................. 295 Chapter 2 - Margaret Duguid ........................................... 325
Chapter 3 ............................................................................... 297 Chapter 3 - Eliza Dollard & Lilian M Abbo ..................... 326
Chapter 4 .............................................................................. 299 Chapter 4 - Conor Jamieson ............................................. 327
Chapter 5 .............................................................................. 300 Chapter 5 - Paul Pottinger ................................................. 327
Chapter 6 ............................................................................... 301 Chapter 6 - Raheelah Ahmad & Alison Holmes ........... 328
Chapter 7 .............................................................................. 302 Chapter 7 - Nick Brown ..................................................... 329
Chapter 8 .............................................................................. 303 Chapter 8 - Alasdair MacGowan

& Melissa Baxter ........................................................ 329 - 330
Chapter 9 .............................................................................. 304
Chapter 9 - Mark Gilchrist
Chapter 10 ............................................................................ 306 & Orla Geoghegan ..................................................... 330 - 331
Chapter 11 .............................................................................. 307 Chapter 10 - William Malcolm ............................................. 331
Chapter 12 ............................................................................ 308 Chapter 11 - Jacqueline Sneddon ..................................... 332
Chapter 13 ............................................................................. 309 Chapter 12 - Esmita Charani
Chapter 14 .............................................................................. 310 & Peter Davey ............................................................ 332 - 333
Chapter 15 .............................................................................. 311 Chapter 13 - Diane Ashiru-Oredope ................................ 333
Chapter 16 ............................................................................. 312 Chapter 14 - Marc Mendelson ........................................... 334
Chapter 17 ............................................................................... 313 Chapter 15 - Debbie Goff, Celine Pulcini,

Mushira Abdulaziz Enani, Kirsty Buising &
Chapter 18 ............................................................................. 314 Arjun Rajkhowa ......................................................... 334 - 337
Chapter 19 ............................................................................. 315 Chapter 16 - South Africa: Adrian Brink,

Asia: Chand Wattal & Reena Raveendran
Chapter 20 ............................................................................ 316 South America: Anahi Dreser ................................. 338 - 339
Chapter 21 .............................................................................. 317 Chapter 17 - Aoife Fleming ................................................ 340
Chapter 22 ............................................................................ 318 Chapter 18 - Andrew Morris .............................................. 340
Chapter 23 ............................................................................. 319 Chapter 19 - Haifa Lyster ................................................... 341
Chapter 24 ............................................................................ 320 Chapter 20 - Sanjeev Singh .............................................. 341
Chapter 25 ............................................................................ 321 Chapter 21 - David Enoch & Laura Whitney ................... 342
Chapter 26 ............................................................................ 323 Chapter 22 - Sanjay Patel .................................................. 343
Chapter 27 ............................................................................. 324 Chapter 23 - Priya Nori ....................................................... 343
Chapter 24 - Karin Thursky ................................................ 344
Chapter 25 - Enrique Castro Sanchez ............................. 344
Chapter 26 - Debra A Goff ................................................. 335
Chapter 27 - Michael Corley ............................................. 345

PRESIDENT OF BSAC [2015-2018]
PREFACE
Scientists have known for more than half a century that The importance of education to support the development
patients could develop resistance to the drugs used to of knowledge and skill sets across the professions is a key
treat them. Alexander Fleming, who is credited with creating objective of the WHO and national action plans for AMR.
the first antibiotic, penicillin, in 1928, cautioned of the impending The development of relevant educational content and its
crisis while accepting his Nobel prize in 1945: “There is the cost-effective and sustainable delivery globally is also a
danger that the ignorant man may easily underdose himself major challenge. The need to combine traditional and modern
and by exposing his microbes to non-lethal quantities of the methods to deliver this are increasingly relevant to ensure
drug make them resistant.” Since then antibiotics have proved better awareness and penetration into health care systems
one of the most effective interventions in human medicine. Sadly, and communities. This e-book offers a more blended or hybrid
the overuse and misuse of this precious resource have brought approach to stewardship education that builds on the success
us to a global crisis of antimicrobial resistance (AMR). To address of the massive open on line stewardship course launched in
this crisis nearly seven decades after Fleming’s lecture the first 2015, reaching over 40,000 learners.
UN general assembly meeting on drug resistance bacteria was
convened in September 2017.
It is only the fourth time the general assembly has held a VISIT MOOC SITE
high-level meeting for a health issue. The UN secretary general,
Ban Ki-moon, said antimicrobial resistance is a “fundamental
threat” to global health and safety. He went on to say “If we
fail to address this problem quickly and comprehensively, The ebook also compliments new on line learning resources
antimicrobial resistance will make providing high-quality from WHO
universal healthcare coverage more difficult if not impossible.
It will undermine sustainable food production and put the
sustainable development goals in jeopardy.” Just before
VISIT WHO SITE
world leaders convened for the meeting, all 193 member
states agreed in a declaration to combat the proliferation of
antibiotic resistance.
which provides a more traditional approach to simple prudent
The need for the solution to AMR requiring a “One Health” prescribing competencies and how they can be applied to
approach is well accepted. The importance of reducing common clinical scenarios, and the CDC programme
overuse and misuse of antibiotics by promoting prudent use is
one fundamental component of this solution - the concept of
antimicrobial stewardship. In the human population, ensuring
prudent prescribing across different communities and settings, in VISIT CDC PROGRAMME SITE
different patient populations, in diverse geographies, resources
and cultures requires a truly innovative, flexible, collaborative
and cross-disciplinary approach. As a global community only by
and ESGAP.
innovating and adapting and adopting the resources we have
available to us can we effect true transformational change in
prescribing practice.
Those of you who wish to seek an overview of global VISIT ESGAP SITE
stewardship may wish to access the plenary presentation on
the subject at ESCMID in 2017:
VIEW SLIDE SET
< RETURN TO CONTENTS < RETURN TO START OF CHAPTER

PREFACE
This educational resource is complimented by the availability of

news items and literature in relation to stewardship from CIDRAP.
INTRODUCTORY VIDEO
BY PROFESSOR DAME
VISIT CIDRAP WEBSITE SALLY DAVIES
This book provides significantly expanded content and

WATCH VIDEO
experience in relation to a broader stewardship context- for
example, stewardship in specific populations, different countries
as well as the role of different professions in stewardship
to political and media engagement. We hope this book has This e-book does not aim to provide a comprehensive
something to offer everyone practicing in this area. traditional textbook of stewardship nor a comprehensive
Therefore, The British Society for Antimicrobial Chemotherapy state of the art review of the literature supporting stewardship.
[BSAC] in collaboration with ESGAP are very pleased to present Instead, the focus is on application to clinical practice with
this e-book on Global Antimicrobial Stewardship that is relevant illustrations of good practice articulated through case studies,
to health care professions working in preventing and managing stories, videos, podcasts, presentations, practical narratives
infection across the healthcare communities and health care and self -assessment exercises. We hope you find it informative,
facilities. It aims to support health care professionals, or teams, engaging and enjoyable. Above all we hope it supports
or policy makers interested in learning about bringing the your practice.
principles of stewardship to the bed side.
DILIP NATHWANI OBE

Editor in Chief
Physician and Educator
President of BSAC [2015-2018]
SOLUTIONS
KEY ANTIMICROBIAL STEWARDSHIP SOLUTIONS WHICH
WILL BE A RECURRING THEME IN THIS BOOK
Regulation and legislation
Accreditation
Surveillance - resistance and consumption
Stewardship
- Structures + processes = outcomes [S+P=O]
- Implementation [changing systems and organisations, understanding
context, cultures and behaviours]
- Evaluation using data for improvement and scrutiny [metrics]
- Feedback, education and action
- Reflect/review/renew
- Sustainability and further change/innovation
11 ANTIMICROBIAL STEWARDSHIP From Principles to Practice

CHAPTER 1
AUTHOR: DILIP NATHWANI
OVERVIEW OF AMR
Learning outcomes are statements
THE AIM OF THIS
INTRODUCTORY of what a student is expected to
CHAPTER IS TO:
Define antimicrobial and
know, understand and/or be able
antibiotic resistance in the
human population.
to demonstrate after completion
Describe the core reasons of a process of learning
for why it occurs.
Outline the global

epidemiology of key
antibiotic resistant bacteria,
LEARNING OUTCOMES
antimicrobial consumption in On completion of this chapter, the participant should be able to:
humans and current • define and explain the differences between antimicrobial and antibiotic resistance
limitations of the data.
• outline the drivers for resistance
Outline the clinical and • outline the global epidemiology of key antibiotic resistant pathogens and
economic impact of drug antibiotic consumption
resistant infections and
• explain the clinical and economic impact of drug resistant infections and health care
impact of health care
acquired infections
acquired infections.
• list some definitions of antimicrobial stewardship and goals of stewardship programmes
THE CHAPTER • identify and communicate the core elements of infection control and stewardship
WILL ALSO DEFINE practice in the context of a fictitious outbreak of a drug resistant health care
acquired infection
Core strategies to combat
• reflect of the relevance of these elements to their practice
AMR.
Antimicrobial stewardship
and its goals in the context
of the “real world” setting.
Introduce the concept

through use of a fictional
outbreak of a multi-drug
resistant infection and
the role of individuals and
healthcare professional in
meeting this challenge.

CHAPTER 1 - OVERVIEW OF AMR
DEFINE ANTIMICROBIAL AND ANTIBIOTIC

RESISTANCE IN THE HUMAN POPULATION
There are many different compounds that can inhibit the growth
of microorganisms, and many terms that are used to categorize
ANTIMICROBIALS
such compounds. ‘Antimicrobials‘, ‘antibacterials’ and ‘antibiotics’
are commonly used terms that can sometimes be used
interchangeably, but there are important differences between
ANTIBIOTICS/ ANTIVIRALS
these words ANTIBACTERIALS
Antimicrobial is derived from the Greek words anti (against), against bacteria, e.g. against viruses, e.g.
mikros (little) and bios (life) and refers to all agents that act drugs for bacteria drugs for herpes
against microbial organisms, i.e. bacteria, viruses, parasites pneumonia and HIV
and fungi.
Antibiotics is derived from the Greek word anti (against) and

biotikos (concerning life). The word “antibiotic” refers to
substances produced by microorganisms that act against
another microorganism. Strictly speaking, antibiotics do not
include agents that are produced by chemical or biochemical ANTIPARASITIC ANTIFUNGALS
AGENTS
synthesis. However for simplicity, synthetic or semi-synthetic
variants (such as quinolones) are usually included under the term against parasites, against fungi, e.g.
antibiotics. In this book the term antibiotic is used for naturally e.g. drugs for drugs for yeast
malaria infections
produced and synthetic compounds that are active against
bacteria, mainly those that have been approved for treatment of
bacterial infections in humans and/or animals.
In contrast, the term “antimicrobials” include all agents that act

against all types of microorganisms – bacteria (antibacterial),
viruses (antiviral), fungi (antifungal) and parasites such as FIGURE 1
protozoa and helminths (antiparasitics) Adapted from Source: http://www.reactgroup.org/toolbox/category/
understand/antibiotics/what-are-antibiotics/
WHAT IS ANTIMICROBIAL RESISTANCE?

Antimicrobial resistance is resistance of a microorganism to an
antimicrobial drug that was originally effective for treatment of ANTIBIOTIC RESISTANCE IS A NATURAL
infections caused by it. AND ACQUIRED PROBLEM
Resistant microorganisms (including bacteria, fungi, viruses The evolution of resistant strains is a natural phenomenon that
and parasites) are able to withstand attack by antimicrobial occurs when microorganisms replicate themselves erroneously
drugs, such as antibacterial drugs (e.g. antibiotics), antifungals, or when resistant traits are exchanged between them. The
antivirals, and antimalarials, so that standard treatments pathways to synthesize antibiotics have been around for
become ineffective and infections persist, increasing the risk millions of years. For example, some microorganisms in the
of spread to others. environment produce antibiotics naturally and they are used
for communication and to compete with other organisms in
WHAT IS THE DIFFERENCE BETWEEN their environment for space and resources. The organisms that
ANTIBIOTIC AND ANTIMICROBIAL produce natural antibiotics of course have to be able to protect
RESISTANCE? themselves against the action of that antibiotic, and often carry
resistance mechanisms.
Antibiotic resistance refers specifically to the resistance to
antibiotics that occurs in common bacteria that cause infections. Other organisms in the same environment will also evolve
Antimicrobial resistance is a broader term, encompassing over time and resistant variants may be selected since they
resistance to drugs to treat infections caused by other microbes can survive nearby the antibiotic-producing organisms.
as well, such as parasites (e.g. malaria), viruses (e.g. HIV) and Therefore, even before the introduction of antibiotics as
fungi (e.g. Candida). medicines, antibiotic resistance mechanisms could be found

HOW DO ANTIBIOTICS WORK?
TOOLKIT Antibiotics function by disrupting essential processes or

structures in the bacterial cell. This either kills the bacterium or
RESOURCE slows down bacterial growth. Depending on these effects
an antibiotic is said to be bactericidal or bacteriostatic. A
bactericidal antibiotic kills the bacteria while the bacteriostatic
A SUMMARY OF ANTIBIOTIC RESISTANCE antibiotics stops bacterial growth but does not kill the bacteria.
DEFINITIONS, IMPACT AT AN INDIVIDUAL, The human immune system is then needed to clear the infection.
POPULATION LEVEL IS SUMMARISED There are several different classes of antibiotics. These can have
BELOW completely different bacterial targets or act on the same target
Antimicrobial resistance and consumption factsheet but at a different site. In principal, there are three main antibiotic
for health professionals targets in bacteria [See toolkit resource] :
• The cell wall or membranes that surrounds the bacterial cell

FOR ADDITIONAL INFORMATION ABOUT
• The machineries that synthesizes the nucleic acids DNA
RESISTANCE AND USE OF ANTIBIOTICS
and RNA
IN ANIMALS AND AGRICULTURE AND THE
ENVIRONMENT: • The machinery that synthesizes proteins (the ribosome and
associated proteins)
Review on Antimicrobial Resistance: Antimicrobial
in agriculture and the environment: reducing These targets are absent or different in the cells of humans
unnecessary use and waste and other mammals, which means that the antibiotics usually
do not harm our human cells but are specific for bacteria.
Different antibiotics and how they work are illustrated in
this video.
in environmental bacteria and as protective measures in
antibiotic producing microbes.
Antibiotic resistance is not common in pathogenic bacteria.

During the eight decades or so that humans have used ANTIBIOTICS MECHANISMS
antibiotics, antibiotic resistance has become prevalent in OF ACTION
environmental and pathogenic bacteria alike. Massive use of
antibiotics within the health care, veterinary and agricultural
sectors has and continues to be prevalent creating a strong
WATCH VIDEO
selection pressure for resistant bacteria. Selective pressure
is any phenomena which alters the behaviour and fitness of
living organisms within a given environment. It is the driving
force of evolution and natural selection.
Human use of antibiotics has also resulted in an accumulation

of these drugs in many environments, where antibiotic
resistant bacteria can flourish. This has also resulted in
selection and spread of bacteria that are resistant to several
different antibiotics.
Adapted from: http://www.reactgroup. org/toolbox/category/

understand/how-did-we-end-up-here-understand/abr-is-a-natural-
phenomenon/

WHERE DOES RESISTANCE OCCUR AND • Alternatively, they can receive resistance genes from other
HOW DOES RESISTANCE HAPPEN? bacteria nearby.
The emergence of resistance occurs in our microbiota and is This process is called horizontal gene transfer.
a unique phenomenon associated with antimicrobials. If a resistance mechanism [mechanisms of resistance outlined
The term gut microbiota refers to the aggregate of all in the video below] gives an advantage to the bacterium it may
microorganisms that colonise the gastrointestinal tract including be maintained, and will be passed on to coming generations as
bacteria, viruses, and eukaryotes. The collective genome of the the bacterium divides, or be passed along by horizontal transfer
gut microbiota, the microbiome, is estimated to contain more by human contact, in food and water, sometimes by respiratory
than 3-5 million different genes exceeding the genome of the droplet, and across borders through travel and trade.
human body approximately more than a hundred-fold. The
human gut microbiota is a host-specific ecosystem, which is, WHAT ARE THE DRIVERS FOR RESISTANCE
to some extent inherited, critically matures in early childhood AND POTENTIAL APPROACHES TO TACKLE
and affects central physiological and pathophysiological RESISTANCE?
mechanisms in the host. It is well known that antibiotics even
At the beginning of the 21st century, antimicrobial resistance
if taken appropriately can shift the gut microbiota to a state
is common, has developed against every class of antimicrobial
termed dysbiosis characterised by many things including
drug, and appears to be spreading into new clinical niches.
loss of diversity, changes in metabolic capacity and reduced
The determinants that are likely to influence the future
colonisation resistance against invading pathogens. Excessive
epidemiology and health impact of antimicrobial resistant
and inappropriate use, for example use of broad spectrum
infections are many and include:
agents, will have a greater impact on dysbiosis which will
promote the horizontal transfer of resistance genes and fuels the excessive use and misuse of antimicrobial drugs accelerates
the evolution of drug-resistant pathogens and the spread the emergence of drug-resistant strains, poor infection control
of antibiotic resistance. Carriage of resistant bacteria in practices, inadequate sanitary conditions and inappropriate
our microbiota can persist for many months, and the risk of food-handling, poverty, lack of or inadequate diagnostics
prolonged carriage is increased by further antibiotic use. tests, use and misuse of antibiotics in agriculture and the
environment, travel and other factors encourage the emergence
Antibiotic resistance is how bacteria protect themselves against
and further spread of antimicrobial resistance. Recognising and
the effects of an antibiotic. Two common ways are by pumping
understanding these factors [See toolkit resource] will ultimately
the antibiotic out of the bacterial cell or by producing molecules
optimize preventive strategies for an unpredictable future.
that can destroy the antibiotic. Other methods are discussed in
Some of these determinants have informed the schematic that
video below.
highlights 10 key interventions needed to tackle AMR: [figure 2].
The video below provides a simple but engaging animated

WATCH VIDEO ON THE narrative of how resistance has come about, spread, the lack
MECHANISMS OF of new antibiotic development and how current and future
antibiotics they may be preserved- the concept of stewardship.
ANTIMICROBIAL RESISTANCE
In the presence of the antibiotic, only non-susceptible i.e.

resistant bacteria will survive or at least multiply faster WATCH ANIMATED VIDEO
than susceptible bacteria and increase in numbers.
Clinical resistance means that a bacterium can grow in the

antibiotic concentrations reached in the body during treatment
leading to likely treatment failure.
Bacteria have two alternative pathways to acquire all types of

TOOLKIT RESOURCE
resistance: PDF ARTICLE
• Random changes in the bacterial DNA (mutations) may Antimicrobial Resistance determinants and future control
provide resistance by chance Harbarth and Samore Emerging Infectious Diseases

TACKLING ANTIMICROBIAL
RESISTANCE ON TEN FRONTS
Public Sanitation
awareness and hygiene
Antibiotics in
Vaccines and
agriculture and
alternatives
the environment
Rapid
Surveillance
diagnostics
Human capital Drugs
Global International
Innovation Fund coalition for action
FIGURE 2
From http://amr-review .org/file/437

WHAT ARE THE DRIVERS FOR THE USE

AND MISUSE OF ANTIBIOTICS?
Since this e-book is primarily concerned about the role
of antibiotic use and misuse in AMR it is useful to briefly
understand the antimicrobial prescribing determinants across
the healthcare communities [e.g. ICU, hospitals, community etc.]
and different geographical and resourced settings.
For example, in the ICU several factors drive excessive
and misuse of antibiotics. These are outlined in figure 3.
Pharmaceutical
Severly ill
marketing
patients
Little pressure Guidelines:
functional Early initiation of
reserve antibiotics
Fear of missing HEAVY NUMEROUS Local or

a life-threatening ANTIBIOTIC INFECTIOUS systemic immune
infrection USE COMPLICATIONS dysfunction
Diagnostic Unavailability
uncertainty of ID
specialists Breaches
Lack of
of natural
knowledge
barriers
SELECTION ANTIBIOTIC BROAD-SPECTRUM

PRESSURE RESISTANCE ANTIBIOTICS
FIGURE 3
Intensive Care Med

DOI 10.1007/s00134=015-3978-8
Causes and consequences of heavy antibiotic use
in the intensive care unit. ID infectious diseases

The drivers for prescribing in the community and community setting perspective are important as 80% of
outpatient setting are outlined in a brief video by Professor all human antibiotic prescribing occurs here. Understanding
Stephan Harbarth. these drivers is critical to developing and effective
The determinants of prescribing in lower income countries, implementation of stewardship interventions. These are
from a prescriber [See toolkit resource], dispenser and summarized in figure 4.
POOR USE OR ANTIBIOTICS BY PRESCRIBERS, DISPENSERS, COMMUNITY
CULTURAL LACK OF UNTRAINED MARKETING

BELIEFS APPROPRIATE SOURCES INFLUENCES
& TRADITIONS KNOWLEDGE OF ADVICE
INCORRECT ECONOMIC FEAR OF POOR PATIENT/

NORMS/ FACTORS CLINICAL CUSTOMER
MODELS & INCENTIVES OUTCOMES DEMAND
SENIORS
OTHERS MENTIONED:
REGULATION / SUPERVISORY SYSTEMS / COMMUNICATION
/ UNSTABLE DRUG SUPPLY / LABORATORY SERVICES
FIGURE 4
Adapted from Soc. Sci. Med 2003; 57:733-44
DRIVERS OF ANTIBIOTIC MISUSE TOOLKIT RESOURCE

AND ABUSE IN THE OUTPATIENT PDF ARTICLE
SETTING: VIDEO INTERVIEW the evidence to support the determinants of prescribing
in low income countries
WITH PROFESSOR STEPHAN
HARBARTH
WATCH VIDEO

THE GLOBAL EPIDEMIOLOGY OF

ANTIBIOTIC RESISTANCE AND
CONSUMPTION IN HUMANS TOOLKIT RESOURCE
The global epidemiology of antibiotic consumption and PDF ARTICLES
resistance through surveillance is patchily delineated Systematic review and meta-analysis of the effects
of antibiotic consumption on antibiotic resistance
Data from resource rich settings and hospitals is generally better
compared to that in the community and resource limited settings.
State of the World’s antibiotics 2015 report
Investment in better surveillance in all settings has
been identified as a priority for improving AMR. However, it is
WHO Global Action Plan
accepted that the overall global burden of AMR is greater
in the community as opposed to the hospital setting. SITE LINK
The link between resistance and antimicrobial consumption has Resistance Map – Interactive map of resistance
been well established [See toolkit resource #1]. and consumption.
A recent state of the world report [See toolkit resource #2] on

antibiotic resistance and consumption provides a detailed and
global review of the subject. However, good quality surveillance
of both is critical and a significant limitation in many parts of the WHAT ARE THE CLINICAL AND ECONOMIC
world as recognized in the WHO Global Action Plan [See toolkit IMPACT OF DRUG RESISTANT INFECTIONS
resource #3]. AND IMPACT ON HEALTH CARE ACQUIRED
INFECTIONS?
Whereas such reports are very valuable in providing insight
into resistance and prescribing the introduction of novel Drug resistance in the context of antibiotics is when the
and interactive resistance map [See toolkit resource #4] that effectiveness of an antibiotic is reduced against a bacterium.
allows interactive exploration of antimicrobial resistance and A drug resistant infection is one that does not respond to the
consumption will facilitate the presentation of more detailed antibiotic treatment due to the presence of antibiotic resistance
and up to date information that will support clinicians and Drug resistant infections were previously associated
policy makers to analyse resistance and consumption patterns. predominantly with hospitals and care settings, but over
These and locally collected data should be the basis for the last decade resistant infections have been seen in the
informing clinical practice, guidance & policy. An example is wider community too, including long-term care facilities for
illustrated below. elderly people. With resistance on the rise, we stand to lose
The current global position on the availability of data that is of the immense ground we have gained in the last century.
good quality and consistent with other datasets is suboptimal This includes: 1) our fight against life threatening infectious
and one of the key recommendations of the Conscience of diseases such as pneumonia, 2) our battle against conditions
Antimicrobial Resistance Accountability [CARA] declaration. such as cancer, where antibiotics are crucial in helping
CARA: The conscience of antimicrobial resistance accountability chemotherapy patients avoid and fight infection; and 3) huge
The Center For Disease Dynamics, Economics & Policy (2016); advances in surgical procedures like organ transplants and
caesarean sections, which have now become routine and
relatively low risk, thanks to our ability to effectively stave off
or treat acute infections with antibiotics.
VISIT SITE When looking at the impact of drug resistant infections a
number of outcomes need to be considered . Such analysis is
complex and to ensure robustness of quality the methodological
considerations require particular attention. These are outlined in
figure 5.

The impact on the individual patient, including those in the

community, is salutary and influential in articulating the impact
even non-life threatening infections to practitioners. This is
TOOLKIT RESOURCE
illustrated by in figure 5 and the overall subject is reviewed in a SITE LINK
presentation. See resource toolkit. Celine Pulcini – BSAC workshop
At an individual patient level there is emerging evidence of
the impact of antibiotic resistance. For example, for simple
uncomplicated urinary tract infection laboratory reported urinary
resistant isolated has the following impact : Adapted from
McNulty et al. J. Antimicrob. Chemother. (2006) 58 (5):
1000-1008
PATIENTS WITH
RESISTANT UTI SUSCEPTIBLE UTI P-VALUE
Median time to
7 days 3 days 0.0002
symptom resolution
Symptom resolution
at 5 days
28% 68% 0.0002
Re-consultation
in first week or less
17 / 39% 17 / 6% <0.0001
Significant bacteriuria
at one month
8 / 42% 23 / 20% 0.04
POINTS TO CONSIDER WHEN READING ANTIMICROBIAL RESISTANCE OUTCOME STUDIES
TYPE OF OUTCOME
Mortality In-hospital only Perspective of study

In-hospital and after discharge Hospital Hospital morbidity, morality and cost
All-cause Third-party payer In and out-of-hospital health care costs
Attributable to infection Patient Decreased functional status, loss of
work and decreased availability of
Morbidity Length of stay antibiotic therapy
Intensive care unit admission Society Total health care costs and loss of
Need for surgery or other procedures classes of antibiotics
Activity level at discharge
Comparison group
Loss of functional time
(missed work and activities) Not infected Interpret as impact of added infection
Infected with Interpret as impact of resistance
Economic Hospital cost susceptible strain
Hospital charges Colonised with Interpret as the impact of progressing
Resource utilisation resistant strain from colonisation to infection
Health care costs Factors that Adjustment for variables, including
improve quality length of stay, severity of illness and
complications before infection
FIGURE 5
Adapted from George M. Ellopoulos et al. Clin Infect Dis. 200;:36:1433-1437

by 2050
WHAT IS THE ECONOMIC IMPACT OF AMR?

A review of Global Risk by the world economic forum
Europe
390,000
North
America
ACCESS FORUM 317,000
Asia
4,730,000
Africa
4,150,000
provides a global snapshot of the costs, impacts and burden of Oceania
Latin 22,000
antibiotic-resistant bacteria across the globe. This illustrates the America
392,000
current burden. Future death and economic burden has been
forecasted through modelling studies.
AMR’s impact on World GDP
Mortality per 10,000 population
in trillions of USD
number of deaths
5 6 7 8 9 10 >
VIEW TACKLING DRUG-

AMR’s impact on World GDP
RESISTANT INFECTIONS
in trillions of USD
DOCUMENT
2040
2020
2050
2030
0 2014
These powerful data underline the significant burden of these
Total GDP loss
infections, often to the most vulnerable and least resourced
populations of the world. For example, fig 6 provides a global
$100.2 trillion
2040
2020
2050
2030
2014
-2$T
snapshot of the mortality and economic impact on GDP of
0
antibiotic-resistant bacteria across the globe.
Total GDP loss
The fact that 2-3.5% of the global GDP would fall in 2050
because
The Review on ofResistance,
Antimicrobial inactionChaired
is a by
sobering
Jim O’Neill thought that should inform, -4$T 13
$100.2 trillion
The Review on Antimicrobial Resistance, Chaired by Jim O’Neill
-2$T
global action through investment. The economic impact of
specific and common drug resistant infections as opposed to
susceptible infections has suggested increased costs outlined -6$T
in Figure 7. The impact of these infections on mortality, length -4$T
of stay and cost is outlined in Figure 8. These data, supported

by local data, are helpful for justification of the value of clinical
-8$T
stewardship programmes and should inform business cases. -6$T
See toolkit resource. FIGURE 6
From http://amr-review .org/file/437
-10$T
-8$T
TOOLKIT RESOURCE
SITE LINK -10$T
Business case
10 The Review on Antimicrobial Resistance, Chaired by Jim O’Neill
10 The Review on Antimicrobial Resistance, Chaired by Jim O’Neill

EXCESS COSTS ATTRIBUTABLE TO INFECTIONS WITH RESISTANT ORGAMISMS VS.

INFECTIONS WITH SUSCEPTIBLE ORGANISMS
RESISTANT ORGANISM CONTROL RANGE OF EXCESS COST*
Methicillin-resistant Staphylococcus aureus Methicillin-susceptible S.aureus $695-$29 030 [21,22,24-36]
Vancomycin-resistant Enterococcus Vancomycin-susceptible Enterococcus $16 711-$60 988 [40-47]
Resistant Pseudomonas aeruginosa Susceptible P. aeruginosa $627-$45 256 [48-49]
Resistant Acinetobacter baumannii Susceptible A. baumannii $5336-$126 856 [23,50-52]
Multiple organisms Susceptible $9372-$18 990 [12,53,54]
ESBL-producing Enterobacteriaceae Non-ESBL-producing Enterobacteriaceae $3658-$4892 [56,57]
ESBL, extended-spectrum ß-lactamase.

* Includes both adjusted and unadjusted estimates; includes only studies reporting cost in US dollars.
FIGURE 7
Adapted from CMI 2014: 20:973-979

IMPACT OF ANTIMICROBIAL RESISTANCE
ON STACKHOLDERS RELATED TO HEALTH
PATIENT PAYS MORE. PATIENT / PAYER
PATIENT, HOSPITAL AND
HOSPITALS LOSES PAYS MORE.
CLINICIAN ALL ADVERSELY
ON REVENUE FROM HOSPITALS SPENDS MORE
AFFECTED
NEW PATIENT ON ANTIBIOTICS
IMPACT OF ANTIBIOTIC RESISTANCE ON PATIENT MORTALITY, LENGTH OF HOSPITAL STAY
INFECTION AND CAUSATIVE ORGANISM INCREASED RISK OF DEATH (OR) ATTRIBUTABLE LENGHT OF STAY (DAYS)
MRSA bacteremia 1.9 2.2
MRSA surgical infection 3.4 2.6
VRE infection 2.1 6.2
Resistant Pseudomonas aeruginosa infection 1.8 - 5.4 5.7 - 6.5
Resistant Enterobacter infection 5.0 9.0
Resistant Acinetobacter infection 2.4 - 6.2 5 - 13
ESBL-producing or KPC-producing 3.6 1.6-fold increase
Escherichia coli or Klebsiella infection
ESBL, extended-spectrum ß-lactamase; KPC, Klebsiella pneumoniae carbapenemase; MRSA, methicillin-resistant Staphylococcus
aureus; OR, odds ratio; VRE, vancomycin-resistant enterococci.
FIGURE 8
Clin Microbiol Infect 2014; 20: 973-979

STEWARDSHIP AS A SOLUTION
TO COMBAT AMR
AN OVERVIEW OF AMR, ITS
The graphic below helpfully introduces stewardship IMPACT AND POTENTIAL
as one of the six core strategies to combat AMR
SOLUTIONS ARE OUTLINED
An excellent overview of AMR outlining the drivers for AMR,
IN THIS VIDEO
impact and potential solutions is provided within this video.
A state of the art review of the global solutions to AMR is also
available. See toolkit resource. WATCH VIDEO
TOOLKIT RESOURCE
PDF ARTICLE
State of the art review of global solutions for AMT
REDUCE
the need for antibiotics through improved
water, sanitation and immunization
IMPROVE
H hospial infection control
and antibiotic stewardship
CHANGE
incentives that encourage antibiotic overuse
and misuse to incentives that encourage
antibiotic stewardship
REDUCE
and eventually phase out subtherapeutic
antibiotic use in agriculture
EDUCATE
health professionals, policy makers and
the public on sustainable antibiotic use
ENSURE
political commitment to meet the
threat of antibiotic resistance
FIGURE 9

WHAT IS ANTIMICROBIAL STEWARDSHIP

AND WHAT ARE ITS GOALS?
The definitions of stewardship are discussed and the goals of
TOOLKIT RESOURCE
stewardship are outlined in the schematic below. Understanding PDF ARTICLES
and measuring any unintended consequences of stewardship, UK Guideline from NICE
especially harm, is also an important goal.
A number of definitions of antimicrobial stewardship exist. US Guideline from the IDSA

The following two definitions provide a means of articulating
their meaning to patient care and infection practice and the Other country specific or generic guidance
other the focus is on the need for organizational and systems
change. The need to articulate clear goals and their emphasis Booklet on antimicrobial stewardship in the
depending on the target audience is also important. hospital setting
Antimicrobial stewardship has been defined as
“the optimal selection, dosage,

and duration of antimicrobial
treatment that results in the
best clinical outcome for the
treatment or prevention of
infection, with minimal toxicity to
the patient and minimal impact
on subsequent resistance.”
It also can be defined as an
“organisational or healthcare
system-wide approach to
promoting and monitoring
judicious use of antimicrobials
to preserve their future
effectiveness.”
More details of both of these definitions, the UK and US
guidelines and others are available in the toolkit resource PDF
Articles #1, #2, #3. An easy pocket guide to these priniciples as
well as implementation are also available. See toolkit resource
PDF Article #4.

OPTIMISE
PATIENT
SAFETY
IMPROVE
CLINICAL
OUTCOMES
CONTROL
COSTS
PREVENT
UNINTENDED
REDUCE
CONSEQUENCES
RESISTANCE,
CDI, TOXICITY
FIGURE 10
A more clinical definition that perhaps is practical and an

engaging message for clinicians is:

THE RIGHT ANTIBIOTIC
FOR THE RIGHT PATIENT,
AT THE RIGHT TIME,
WITH THE RIGHT DOSE,
AND THE RIGHT ROUTE,
CAUSING THE LEAST HARM TO
THE PATIENT AND FUTURE PATIENTS
FIGURE 11
Adapted from http://www.cdc.gov/getsmart/healthcare/inpatient-stewardship

HOW DOES THIS LOOK IN PRACTICE?

To illustrate an example of AMR, infection control and
stewardship you may wish to watch the following 2 videos.
BILL & FRED - HOW THEY ARE
They aim to encourage you to consider key drivers for AMR AFFECTED BY AN INFECTION
and identify good and suboptimal practice. This reflection will WITH A RESISTANT ORGANISM
prepare you for the more detailed learning in the remainder of
this book.
For your first activity you are asked to watch this video, WATCH VIDEO
which runs for 8 minutes and tells the story of two patients,
Bill & Fred, and how they are affected by an infection with
a resistant organism.
As you watch the video consider the following:
• What deficiencies in infection control and clinical practice

are depicted in the video? RESPONSE TO THE OUTBREAK
• What are the key drivers for resistance? BY THE HOSPITAL TEAM
• What are the key prescribing issues worthy of investigation
in this video? WATCH VIDEO
Now watch part two of our scenario. The video runs for 10
minutes and shows the response to the outbreak by the
hospital team.
*Consider the strengths and weaknesses of the incident

management team. Think particularly about how they tried to
engage clinicians and their attempts at measuring compliance
with good practice. The prescribing issues that may be worthy
of investigation and the strengths and weaknesses of the
response to the outbreak.
*Were there any deficiencies in infection control and clinical

practice, and drivers for resistance.
[DISCLAIMER - All characters appearing in this work, both parts

1 & 2, are fictitious. Any resemblance to real persons, living or dead,
is purely coincidental}

CHAPTER 2
AUTHOR: MARGARET DUGUID
ANTIBIOTIC USE AND MISUSE

ACROSS THE RANGE OF
HEALTHCARE COMMUNITIES
AND THE DRIVERS/
DETERMINANTS OF MISUSE
THE AIM OF THIS CHAPTER IS TO:
LEARNING OUTCOMES
On completion of this chapter, the participant should be able to:
To consider antibiotic consumption and prevalence of
use-in primary and secondary care • Explain changes in the use of antibiotics globally and the
- Global consumption of antibiotics drivers of the changes
- Antibiotic use in the community setting • Describe the prevalence and volume of antibiotic use in
• Prevalence of use community, hospitals and long-term care aged care settings
• Prescribers • List the most common antibiotic agents prescribed in
• Antibiotic consumption community and hospital settings
• Common indications for use in the community • Describe trends in antibiotic use in hospital settings
• Patterns of use • Define misuse of antibiotics
- Antibiotic use in the hospital setting
• List common indications where antibiotics are inappropriately
• Prevalence of use
prescribed/used.
• Hospital consumption
• List the key drivers/determinants of antibiotic use
• Trends in hospital antibiotic use
• Variation in use • Reflect on the relevance of these elements to their practice
• Indications for use
• Intensive care units ANTIBIOTIC CONSUMPTION AND
- Long-term care PREVALENCE OF USE IN PRIMARY AND
The misuse of antibiotics SECONDARY CARE
- What misuse includes Measuring and monitoring antibiotic use is an important
- Inappropriate use in community component of efforts to control the emergence of antimicrobial
- Inappropriate use in hospital resistance (AMR) and can be used to:
- Inappropriate use in intensive care units
• identify areas where rates of consumption per person is high
- Non-prescription use of antibiotics
and the potential for development of resistance greatest;
Determinants of antibiotic prescribing and misuse
• inform initiatives to preserve the efficacy of antibiotics; and
• provide a baseline from which to assess effectiveness of

CHAPTER 2 - ANTIBIOTIC USE AND MISUSE ACROSS THE RANGE OF HEALTHCARE COMMUNITIES AND THE DRIVERS/DETERMINANTS OF MISUSE
efforts to reduce antibiotic consumption. GLOBAL CONSUMPTION OF ANTIBIOTICS

Many countries: The systems mentioned provide useful data on the volume (rate
• have systems to measure national antibiotic use at both of consumption) of antibiotic use. They show that antibiotic use
community and hospital levels and several countries has been increasing globally - over the period 2000-2010 overall
produce annual reports of AMR and antimicrobial (mainly use is estimated to have increased by 35%. This increase has
antibiotic) use been greater in low and middle-income countries. India, China
and the US used the most antibiotics over all. Five countries
• contribute to multi-country antimicrobial use data collections/ (Brazil, Russia. India, China and South Africa) accounted for 76%
networks e.g.: of the increase in global consumption. This increase has been
o European Surveillance of antimicrobial Consumption driven by factors such as economic growth and increased access
Network to antibiotics. High income countries use more antibiotics on a
https://ecdc.europa.eu/en/publications-data/antimicrobial- per capita basis.
consumption-database-esac-net
and
o the Organisation for Economic Co-operation and

Development (OECD)
http://www.oecd.org/els/health-systems/antimicrobial-
resistance.htm
Most systems report combined paediatric and adult data.

See chapter 22 for specific information on paediatric data.

TOOLKIT RESOURCE
SITE LINK
FIGURE 1
Antibiotic consumption levels in OECD countries. Percentage change in antibiotic consumption per capita 2000-2010
Center for Disease Dynamics, Economics & Policy.

The state of the world’s antibiotics.2015.
Penicillins and cephalosporins account for around 60% of total
Interactive Map on antibiotic consumption at a global antibiotic consumption. Between 2000-2010 their usage
country and global level. Center for Disease increased by around 40% as did carbapenems, a reserve group
Dynamics, Economics and Policy. of antibiotics. This increase in carbapenem use along with a 13%
increase in the last resort agents polymixins (e.g. colistin) and a
doubling of glycopeptide (e.g. vancomysin) use is attributed to
PDF ARTICLE
the rising rates of antibiotic resistance and development of multi
European Centre for Disease Prevention and drug resistant organisms.
Control. ESAC-Net Surveillance data 2016
ARTICLE
Country reports on antimicrobial use resistance
surveillance

ANTIBIOTIC USE IN THE

COMMUNITY SETTING
The majority of antibiotic use, around 80%, occurs in the
community, prescribed in settings such as outpatient clinics,
health posts and general practice.
Prevalence of use
Prevalence of antibiotic use in the community varies between
countries from less than 20% to over 40% of the population
dispensed at least one antibiotic each year.
Prescribers
In Europe, Australia and Canada general practitioners prescribe
the majority of antibiotics in the community, dentists account for
3 -10% and nurses and other health professionals < 6%. In the US
general practitioners prescribe the most outpatient prescriptions
(22%in 2014) closely followed by physician assistants and nurse
FIGURE 2
Centre for Disease Dynamics, Economics & Policy Interactive practitioners (20%), then a range of medical specialists. Dentists
Resistance Map. https://resistancemap.cddep.org/ are 5th highest prescribers at 9%.
Outside Northern Europe, US and Australasia 19% to 100% of

If you would like to know more watch this PPT presentation antibiotics are supplied without prescription.
“Global Antibiotic Consumption” by Margaret Duguid, Antibiotic consumption
Standardised units of measure are used to compare
antibiotic use.
DOWNLOAD SLIDE SET Common units of measure of antimicrobial consumption
Units Limitations
The most common unit DDDs are not suitable for

is the World Health determining antimicrobial
Organisation’s (WHO) use in children.
defined daily dose (DDD).
Defined as the assumed Doses used for some
average maintenance dose agents (e.g. penicillins) may
per day for a drug used for vary between countries
its main indication in adults. and may differ from WHO
DDDs allow standardised defined DDDs.
comparisons between
drugs and can be used in
community and hospital
settings
Community measures Packs per 1000 inhabitants

FIGURE 3 DDD per 1000 inhabitants does not take into account
SWEDRES/SVARM 2016 Consumption of antibiotics and occurrence dosage information
Prescriptions or packs
of antibiotic resistance in Sweden, Scottish antimicrobial resistance
dispensed per 1000
and use in humans 2015, AURA 2017 - Second Australian report on
antimicrobial use and resistance in human health inhabitants.

Patterns of use
Hospitals measures DDD per1000 patient days
DDD per 100 or 1000 bed do not take into account the
days case mix or infection rates
in hospitals.
DDD per 1000 admissions
(or discharges)
DDD per admission (or
discharge) is useful where
length of stay is short
DDDs per bed-days is

more useful in units where
lengths of stay are longer
ASP METRICS EXAMPLES
• Amongst the OECD countries the average consumption

of antibiotics in 2014 was around 20.5 DDDs per 1000
inhabitants.
• There is significant variation in consumption rates across

countries– up to a 4.4 fold difference.
VIEW FIGURE
Human antimicrobial consumption in OECD countries 2005 and 2014
Within countries there are significant regional differences in FIGURE 4

prescribing rates for antibiotics with some regions prescribing Center for Disease Dynamics, Economics & Policy. The state of the
world’s antibiotics.2015
over 2 times that of other regions. These differences cannot be
explained by disease incidence alone.
Whilst penicillins are the most frequently used antibiotics with 30
Use in the community is highest in the very young (0-9 years)
to 60% of use, the pattern of use of other antibiotic groups varies
and the elderly (65+ years).
considerably between countries. For example, cephalosporins
Common indications for use in the community and other beta lactams (including carbapenems) account for
In developed countries, the majority of the use of antibiotics in 0.2% of total community antibiotic use in Denmark compared
the community is for respiratory infections (accounting for 90% of to 22% in Germany, and quinolones, 2% of total community
antibiotic sales in Swedish children), urinary tract infections and antibiotic use in UK compared to 16% in Hungary.
soft tissue infections.
If you would like to know more watch this PPT presentation
Seasonal use “Antibiotic Consumption in the Community” by Margaret Duguid,
Use peaks in winter months, coinciding with season for colds
and influenza, indicating use in upper respiratory tract infections
where infections are mainly viral and antibiotics are not
indicated. DOWNLOAD SLIDE SET

TOOLKIT RESOURCE
SITE LINK
The state of the world’s antibiotics.2015.
Australian Commission on Safety and Quality in

Health Care. AURA: Antimicrobial Use and
Resistance in Australia
Center for Diseases Control. Report on

Europe – Mean 33%, Range 22 – 55%
Antibiotic Use in the United States, 2017: Progress
and Opportunities FIGURE 5
Source: ECDC. Point prevalence survey of healthcare-associated
infections and antimicrobial use in European acute care hospitals
PDF ARTICLE 2011-2012
European Centre for Disease Prevention and Taylor et al Can J Infect Dis Med Microbiol. 2015 Mar-Apr; 26(2): 85–89.
Control. ESAC-Net Surveillance data 2016 Magill et al JAMA 2014 vol. 312, no. 14, pp. 1438-1446
Antimicrobial prescribing practice in Australian hospitals. Results of

2015 National Prescribing Survey
ANTIBIOTIC USE IN THE
HOSPITAL SETTING
Hospital consumption
There are substantial variations in use between countries in The data in this section is drawn from surveillance data and point
terms of volume of antibiotics used and the patterns of use. prevalence studies conducted in European, US and Australian
hospitals.
In 2015 the consumption of systemic antibiotics in European
acute hospitals ranged from 1.0 DDD per 1000 inhabitants per Trends in hospital antibiotic use
day in the Netherlands to 2.9 DDD per 1000 inhabitants per • Most high-income countries have not reported a significant
day in Malta. change in overall inpatient antibiotic consumption in the
Prevalence of use last decade.
On any one day in hospital 22% to 55% of patients in • Penicillins are the most frequently prescribed antibiotic
European hospitals and 50% in US hospitals received one subgroup in many countries followed by other β lactams
or more antibiotics. (cephalosporins, monobactams, carbapenems) and
In the US patients 50% of these patients received 2 or more quinolones.
antibiotics compared with 30% in Europe. • There is the shift towards a greater use of broad spectrum
agents in many countries with increases in 3rd and 4th
generation cephalosporins, beta lactam/beta-lactam inhibitor
combinations and carbapenem use.
VIDEO INTERVIEW WITH DR
• Pencillin – β lactam inhibitor combination products and
SHELLEY MAGILL. ALMOST extended spectrum penicillins accounted for 82% of penicillin
HALF OF PATIENTS RECEIVE use in European hospitals in 2015.
AT LEAST ONE ANTIBIOTIC • Percentage patients receiving carbapenems varies from
WHILST HOSPITALISED <1% to >5% between countries
WATCH VIDEO

FIGURE 6
ECDC https://ecdc.europa.eu/en/publications-data/antimicrobial-use-
european-hospitals

Indications for use

• Most antibiotics are prescribed for treatment of infections
PODCAST: DR ARJUN (68% in European and 78% in US hospitals), surgical
SRINIVASAN ON NATIONAL prophylaxis accounts for around 12% - 19% of inpatient
prescriptions and medical prophylaxis around 8% to 11%.
TRENDS IN INPATIENT ANTIBIOTIC
USE AMONG US HOSPITALS.
LISTEN TO PODCAST
Variation in use
This is significant for some agents. For example:
• Percent of cephalosporins and other beta-lactams (including

carbapenems) prescribed ranges from 7% in UK to 54% in
Bulgaria and in some countries have over taken penicillins as
the most frequently prescribed antibiotic class. See FigureX
• Quinolone use ranges from 4% in UK and Australia to 19%

in Malta.
FIGURE 8
Indications for antimicrobial use in European acute care hospitals
Source: ECDC PPS 2011-2012
LTCF = long term care facility
• Lower respiratory tract infections are the most common

treatment indications followed by urinary tract infections and
skin and soft tissue in higher income countries.
• In lower income countries infections such as lower respiratory

tract infections, malaria and gastrointestinal tract infections
are more prevalent.
Intensive care units

Use of antibiotics is higher in ICUs compared with general wards
as the prevalence of infection in ICUs is higher.
57% of ICU patients in US and European hospitals were

prescribed at least one antimicrobial during their ICU stay.
FIGURE 7
ECDC. ESAC-Net
Surveillance data
November 2016

ALL OF HOSPITAL ICU

TOOLKIT RESOURCE
916 DDD/1000 1479 DDD/1000
SITE LINK
BED DAYS BED DAYS
ECDC. Point prevalence survey of healthcare-
associated infections and antimicrobial use in
SOURCE European acute care hospitals 2011-2012
Antimicrobial use in Australian Hospitals. 2015 Report. https://www.
safetyandquality.gov.au/antimicrobial-use-and-resistance-in-australia/ Australian Commission on Safety and Quality in
NB These figures are for adult patients
Center for Diseases Control.Report on

The increasing presence of multidrug-resistant and extensively
Antibiotic Use in the United States, 2017: Progress
drug resistant organisms in ICU units is driving the use of
and Opportunities
glycopeptides and broad spectrum agents such as piperacillin
and tazobactam, 3rd and 4th generation cephalosporins, PDF ARTICLE
cabapenems and agents of last resort such as colistin.
European Centre for Disease Prevention and
The main drivers for antibiotic use in ICU units have been Control. ESAC-Net Surveillance data 2016
described by Albrich and Harbath. (see chapter 1)
ARTICLES
If you would like to know more watch this PPT presentation
Baggs J, Fridkin SK, Pollack LA, Srinivasan A, Jernigan JA
“Antibiotic Consumption in Hospitals” by Margaret Duguid,
2016, ‘Estimating National Trends in Inpatient Antibiotic
Use among US Hospitals from 2006to 2012’, JAMA Intern
Med, vol 176, no.11, pp1639-1648
DOWNLOAD SLIDE SET Magill SS, Edwards JR, Beldavs ZG, Dumyati G, Janelle
SJ et al 2014 ‘Prevalence of antimicrobial use in US acute
care hospitals May to September 2011’. JAMA, vo
LONG TERM CARE
The prevalence of use of antibiotics in long term facilities such
as aged care homes is very high and as much as 75% of use
estimated to be inappropriate.
AGED CARE (NURSING) HOMES • respiratory tract infections
PREVALENCE OF ANTIMICROBIAL USE VARIATION IN USE

Use is generally higher than in the community • Consumption rates vary between countries
• 50 – 80% of aged care residents receive at least one • 5.9 DDD/1000 residents per day in Germany to 1
course of systemic antibiotics each year 35.7/1000 residents per day in Northern Ireland
• antibiotics are prescribed for around 75–90% of • Patterns of use vary across different countries and are
all infectious episodes influenced by national and regional guidelines
• antibiotics account for almost 40% systemic drugs • Use of parenteral administration ranges from <1% to 7-9%
prescribed
APPROPRIATENESS OF USE
• More than 1 in 10 residents receive an antimicrobial at
• 40 – 75% or antibiotic use is claimed to be inappropriate
any one time
• 30% prescriptions prescribed for > 6 months
COMMON INDICATIONS FOR USE
• urinary tract infections
• skin and soft tissue infections; and

• iv route when oral can be used
TOOLKIT RESOURCE • dose is too high or too low compared to what is indicated
for that patient
SITE LINK • duration is too long or too short
Australian Commission on Safety and Quality in
• duration is > 24 hours for surgical prophylaxis, (except
where guidelines endorse longer duration)
• treatment is not streamlined or changed when
Center for Diseases Control. Report on microbiological culture data become available
Antibiotic Use in the United States, 2017: Progress • prescription of agent for patients with a known allergy
and Opportunities to the agent,
• drug-drug interaction
PDF ARTICLE
• poor patient adherence to the prescribed treatment.
ECDC Point Prevalence Study of Healthcare
Associated Infection and Antimicrobial Use in If you would like to find out more watch this PPT by Margaret
European Long-term Care Facilities 2013 Duguid Insert power point presentation Misuse of antibiotics
ARTICLES
van Buul LW, van der Steen JT, Veenhuizen RB, DOWNLOAD SLIDE SET
Achterberg WP, Schellevis FG, Essink RT, et al. 2012.
“Antibiotic use and resistance in long term care facilities”.
J Am Med Dir Assoc, vol.13, no. 6, pp. 568.e1-13.
Inappropriate use in community
Much of the inappropriate prescribing of antibiotics in the
Lim CJ, Kong DCM, Stuart RL. 2014;” Reducing
community is for infections not caused by bacteria such as colds
inappropriate antibiotic prescribing in the residential care
and influenza and other viral infections, and, in low income
setting: current perspectives”. Clin Interv Aging, vol. 9,
countries, for diarrhoea, malaria.
pp 1-13
• over 50% of antibiotics may be prescribed unnecessarily
in the community for upper respiratory tract infections
• as many as 30% of residents in aged care facilities are

MISUSE OF ANTIBIOTICS prescribed antibiotics when not indicated for asymptomatic
urinary tract infections.
Misuse includes:
Few countries assess appropriateness of antibiotic use at a
• underuse- this is quite frequent in LMIC due to a lack of
national level and consumption data is often used to indicate
access to healthcare services
overuse or inappropriate use. For example, in the community or
• unnecessary use – where an antimicrobial is not indicated outpatient setting:
and there is no health benefit for the patient (e.g. treatment of
• A high seasonal variation of total or specific antibiotic
an upper respiratory infection caused by a virus or an
consumption indicates an unnecessary use of antibiotics for
antibiotic is not recommended)
treatment of viral upper respiratory tract infections.
• inappropriate (or suboptimal) use – where timing,
• variation in consumption and patterns of use across practices,
antimicrobial choice, dose, route, frequency of administration
regional areas or countries can suggest overuse,
or duration of treatment is incorrect. For example:
inappropriate use or use not concordant with guidelines.
• delayed administration in a critically ill patient,
• choice of an antibiotic with an unnecessarily broad

spectrum or too narrow a spectrum
• drug-bug mismatch

bronchitis, COPD infective exacerbations) urinary tract

infections
TOOLKIT RESOURCE • skin and soft tissue infections.
SITE LINK Surgical prophylaxis regimens are commonly prescribed
Australian Commission on Safety and Quality in inappropriately:
• Choice, dose, timing or duration of therapy is suboptimal
* Rates of patients receiving prophylaxis for > 24 hours
Center for Diseases Control. Report on range from 10% to 90%. Best practice is < 5%
Antibiotic Use in the United States, 2017: Progress • In low income countries antibiotics are often prescribed
and Opportunities after surgical procedures, using 7 times more antibiotics.
Inappropriate use in ICU

Dr Katherine Fleming-Dutra, Improving antibiotic
prescribing in outpatient setting podcast
30 - 60% ANTIBIOTIC PRESCRIBING
PDF ARTICLE IN ICU UNNECCESSARY OR
Organisation for Economic Co-operation and INAPPROPRIATE
Development. Antimicrobial resistance.2016
‘Policy Insights’ Suboptimal prescribing in ICU includes: poor choice of antibiotic
(including inadequate first line empirical therapy), use of
ARTICLE redundant combinations of agents, failure to de-escalate therapy
and excessive duration of therapy.
Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartocoes
M, Enns EA et al 2016, ‘Prevalence of inappropriate
antibiotic prescriptions among US ambulatory Care Visits,

2010-2011”, JAMA, Vol. 315, no. 17, pp1864-1873
TOOLKIT RESOURCE
SITE LINK
Inappropriate use in hospital Center for Disease Dynamics, Economics & Policy.
The state of the world’s antibiotics.2015
25% - 50% INPATIENT USE IS ECDC. Point prevalence survey of healthcare-

UNNECCESSARY OR INAPPROPRIATE associated infections and antimicrobial use in
European acute care hospitals 2011-2012
Non-adherence to guidelines is similarly high. PDF ARTICLE

Common reasons for inappropriate prescribing include: antibiotic European Centre for Disease Prevention and
not indicated; spectrum too broad (including continuation Control. ESAC-Net Surveillance data 2016
of initial therapy with broad spectrum agents after results of
susceptibility tests are known), incorrect duration, and incorrect ARTICLE
dose and frequency.
Magill SS, Edwards JR, Beldavs ZG, Dumyati G, Janelle SJ
Doctors in some hospitals prescribed 3 times as many et al 2014 ‘Prevalence of antimicrobial use in US acute
antibiotics as doctors in other hospitals. care hospitals May to September 2011’. JAMA, vol 312, no.
Indications where antibiotics are commonly prescribed 14, pp. 1438-1446
inappropriately or guidelines not followed:
• surgical prophylaxis
• respiratory infections (community acquired pneumonia,

NON-PRESCRIPTION USE OF ANTIBIOTICS • A lack of knowledge of local antimicrobial resistance, gaps in

antibiotic knowledge and/or awareness of available evidence
Whilst many countries have regulations limiting antibiotic
or local or national prescribing guidelines.
prescribing to registered health practitioners these laws are not
enforced in most LMICs and some high-income countries. In • Diagnostic uncertainty and fear of poor clinical outcomes
much of the world antibiotics are sold without prescription. Non- - leading to increased use of broad spectrum agents or
prescription use: unnecessary prescription of antibiotics e.g. for viral infections.
• accounts for 19% - 100% of antimicrobial use outside northern • Sociocultural factors such as patients’ expectation of
Europe, Australasia and the US. receiving an antibiotic and the health professions perception
of that expectation
• Is associated with very short courses (driven by financial
situation), inappropriate antimicrobial and dose choices • Socioeconomic factors such as reimbursement systems and
marketing by the pharmaceutical industry.
• Is driven by poor access to health care
• Inadequate or poorly regulated supply of antibiotics
In some countries substandard or counterfeit antibiotics also
contribute to antibiotic use with little or no benefit. In South
Africa 1 in 5 medicines are estimated to be counterfeit.

TOOLKIT RESOURCE
SITE LINK
The state of the world’s antibiotics.2015
ARTICLE
Morgan DJ, Okeke IN, Laxminarayan R, Perencevich, FIGURE 9
Source: Adapted from Soc. Sci. Med 2003;57:733-44
Weisenburg S. 2011, ‘Non-prescription antimicrobial
use worldwide: a systemic review’ Lancet Infectious
Diseases, vol. 11, no. 9, pp.692-701. Doi:10.1016/S1473-
3099(11)70054-8
DETERMINANTS OF ANTIBIOTIC
PRESCRIBING AND USE
There are many factors that can influence antibiotic use and
negatively affect prescribing behaviour. These are listed in the
diagram below and include: FIGURE 10
• psychosocial determinants such as attitudes, beliefs and
social norms. In hospitals there is a culture and “etiquette”
around prescribing set by senior medical staff that is rooted
in the autonomy of decision making and a culture of medical
hierarchy. Health professionals are often reluctant to question
prescribing decisions of colleagues and in some sectors, such
as private hospitals, senior prescribers have complete
autonomy in deciding what antibiotic to use, how much to use
and for how long.
• Resistance is not seen as a problem important in prescriber’s

own daily practice
FIGURE 11

Drivers of antibiotic prescribing in hospitals differ from those in

the community.
DR STEPHEN HARBARTH.
DRIVERS OF ANTIBIOTIC
MISUSE IN OUTPATIENT
SETTINGS
WATCH VIDEO
Cultural differences in attitudes and expectations, along

with regulation and the accessibility of antibiotics and
diagnostic testing may explain the variation in antibiotic use
between countries. Cultural factors, (patient, practitioner and
organisational) may also contribute to the 2 to 3 times variation
in prescribing within countries and across institutions. The local
drivers of antibiotic use need to be assessed as part of any local
efforts to improve antibiotic use.

TOOLKIT RESOURCE
PDF ARTICLE
Radyowijati A & Haak H. Improving antibiotic use
in low-income countries:An overview of evidence
on determinants.
ARTICLES
Hulscher ME, Grol RPTM, van der Meer JWM 2010,
‘Antibiotic prescribing in hospitals a social and behavioural
scientific approach’, Lancet Infect Dis, vol.10, pp.167-75
Touboul-Lundgren P, Jensen S, Drai J, Lindbaek M 2015

‘Identification of cultural determinants of antibiotic
use cited in primary care in Europe: a mixed research
synthesis study of integrated design ‘Culture is all around
us ‘, BMC Public Health, vol. 15 :908

Bibliography Hulscher ME, Grol RPTM, van der Meer JWM 2010, ’Antibiotic
Center for Disease Dynamics, Economics & Policy. 2015. ‘The prescribing in hospitals: a social and behavioural scientific
state of the world’s antibiotics’. approach. Lancet Infect Dis, Vol.10, pp 167-75
Organisation for Economic Co-operation and Development. Touboul-Lundgren P, Jensen S, Drai J, Lindbaek M 2015
Antimicrobial resistance.2016 ‘Policy Insights’. ‘Identification of cultural determinants of antibiotic use cited
in primary care in Europe: a mixed research synthesis study of
Australian Commission on Safety and Quality in Health Care.
integrated design ‘Culture is all around us ‘, BMC Public Health,
AURA 2017:Second Australian report on antimicrobial use and
vol. 15 :908
resistance in human health.
Radyowijati A and Haak H 2003, ‘Improving antibiotic use in low-
Swedres-Svarm. Consumption of antibiotics and occurrence of
income countries: An overview of evidence on determinants’. Soc
antibiotic resistance in Sweden. 2015
Sci Med, Vol. 57, no. 4, pp 733-44.
Canadian Antimicrobial Resistance Surveillance System Report
2016
Center for Diseases Control. Report on Antibiotic Use in the
United States, 2017: Progress and Opportunities.
Magill SS, Edwards JR, Beldavs ZG, Dumyati G, Janelle SJ et al
2014, “Prevalence of antimicrobial use in US acute care hospitals
May to September 2011”. JAMA, Vol.312, no. 14, pp 1438-1446
Baggs J, Fridkin SK, Pollack LA, Srinivasan A, Jernigan JA 2016,
‘Estimating National Trends in Inpatient Antibiotic Use among
US Hospitals from 2006to 2012’, JAMA Intern Med, vol 176, no.11,
pp1639-1648
Yoon YK, Park GC, An H, Chun BC, Sohn JW 2015, ‘Trends
in antibiotic consumption in Korea according to national
reimbursement data’. Medicine, vol. 94, no. 46 e2100
van Buul LW, van der Steen JT, Veenhuizen RB, Achterberg
WP, Schellevis FG, Essink RT, et al. 2012. “Antibiotic use and
resistance in long term care facilities”. J Am Med Dir Assoc,
vol.13, no. 6, pp. 568.e1-13.
Lim CJ, Kong DCM, Stuart RL. 2014;” Reducing inappropriate
antibiotic prescribing in the residential care setting: current
perspectives”. Clin Interv Aging, vol. 9, pp 1-13.
National Centre for Antimicrobial Stewardship and Australian
Commission on Safety and Quality in Health Care. Antimicrobial
prescribing and infections in Australian residential aged care
facilities; Results of the 2015 aged care National Antimicrobial
Prescribing Survey pilot.
Fleming-Dutra KE, Hersh AL, Shapiro DJ, Bartocoes M, Enns EA
et al 2016, ‘Prevalence of inappropriate antibiotic prescriptions
among US ambulatory Care Visits, 2010-2011”, JAMA, Vol. 315,
no. 17, pp1864-1873
National Centre for Antimicrobial Stewardship and Australian
Commission on Safety and Qualtiy in Health Care. Antimicrobial
prescribing practice in Australian hospitals. Results of 2015
National Prescribing Survey.
Morgan DJ, Okeke IN, Laxminarayan R, Perencevich, Weisenburg
S. 2011, ‘Non-prescription antimicrobial use worldwide: a systemic
review’. Lancet Infectious Diseases, Vol.11, n.9, pp 692-701.
Doi:10.1016/S1473-3099(11)70054-8

CHAPTER 3
AUTHORS: ELIZA DOLLARD & LILIAN M ABBO
WHAT IS ANTIMICROBIAL
STEWARDSHIP?
LEARNING OUTCOMES
THE AIM OF THIS On completion of this chapter, the participant should be able to:
INTRODUCTORY • Appraise what is antimicrobial stewardship and what is prudent antimicrobial prescribing
CHAPTER IS TO:
• Explore opportunities for implementing antimicrobial stewardship programs in acute
Define key principles care hospitals
of prudent antimicrobial
• Discuss possible unintended consequences of antimicrobial stewardship
prescribing.
• Apply key principles of prudent antimicrobial prescribing in acute care hospital scenarios
Outline goals of antimicrobial
stewardship (AMS). WHAT IS ANTIMICROBIAL STEWARDSHIP AND WHY IS
IT IMPORTANT?
Discuss possible unintended
consequences of In this YouTube video animation you will:
antimicrobial stewardship.
UNDERSTAND WHY IS ANTIMICROBIAL

STEWARDSHIP IMPORTANT FOR YOUR
INDIVIDUAL PATIENT AND THE GLOBAL
COMMUNITY
WATCH VIDEO
Case Scenario
A 54 years old female teacher, had a root canal and was prescribed clindamycin to treat a
dental abscess. After 48 hours, she started to feel tired and was not able to go to work that
day. Four days later she started to have watery diarrhoea and abdominal pain and thought
that she had a stomach virus from one of the kids in school.
Within 6 days she was admitted to the hospital in septic shock where she was diagnosed
with severe Clostridium difficile colitis complicated with a toxic megacolon requiring total
colectomy. She consequently developed short gut syndrome dependent on total parenteral
nutrition. She subsequently underwent intestinal transplantation and on post-operative day

CHAPTER 3 - WHAT IS ANTIMICROBIAL STEWARDSHIP?
12, became febrile, septic with intra-abdominal collections, acute IMPACT OF ANTIMICROBIAL STEWARDSHIP
pancreatitis and bacteremia with 4/4 blood cultures growing (AMS) PROGRAMS
gram negative rods. All cultures from blood an abdomen grew
In chapter 1 you learnt about the overall clinical, microbial
Klebsiella pneumoniae:
and economic impact of infections with drug resistant bacteria.
AMS programs have been shown to have significant beneficial
impact on many of these outcomes and include appropriate
antibiotic prescribing, reduction in overall prescribing in some
cases, length of antibiotic therapy, decrease length of stay,
reduced morbidity and mortality and overall a reduction in
healthcare costs. A recent systematic review showed benefits
of AMS on microbial outcomes, the impact for example GNB
infections, an important and key challenge globally is illustrated
in Fig.1 Strategies for AMS programs and evidence for the
impact of process and outcome measures will be summarised
in this eBook.
Is this a frightening scenario? Yes, indeed.

Antibiotic resistance not only happens in acute hospitalised
patients but can start in the community. In this case, an antibiotic
prescribed in the outpatient setting by a dentist lead to
significant complications and possible mortality.
Perhaps you will be the next healthcare provider caring for a
patient with a multidrug resistant infection or, worse (depending
on one’s perspective), you yourself could contract a multidrug
resistant organism for which there is no effective antimicrobial
therapy available. Unfortunately, this is not science fiction,
or a new unknown infection from an exotic land. Antibiotic
resistance is a serious problem worldwide. We use this terms
as resistance to bacteria is common and the focus of this
chapter. There are very limited new options to treat multidrug
resistant gram-negative bacteria, with very few antibiotics in the FIGURE 1
development pipeline. Development of new antimicrobials for http://www.thelancet.com/journals/laninf/article/PIIS1473-
multidrug resistant organisms has to be a public health priority; 3099(17)30325-0/fulltext
nonetheless, "The development of new antibiotics without
having mechanisms to insure their appropriate use is much like
supplying your alcoholic patients with a finer brandy." (Dennis
Maki, IDSA meeting, 1998)

KEY PRINCIPLES OF PRUDENT

ANTIMICROBIAL PRESCRIBING
Modern medicine would not be possible without antibiotics
(Figure 2). These amazing drugs have revolutionised how we
care for patients in the 21st century. We are able to care for
premature babies, critically ill patients with sepsis, transplant
solid organs and provide chemotherapy to patients with cancer
among other miracles. Unfortunately, the appropriate and
inappropriate use of these drugs has consequences.
As global rates of antibiotic resistant infections increase
antibiotic research and development has been dwindling,
resulting in a catastrophic lack of weapons to use in this public
health crisis. In response to this challenge, healthcare workers
on the front lines have been tasked with minimizing unnecessary
and inappropriate prescribing of antibiotics in order to prevent
development of resistance while maintaining or improving
patient outcomes.
Antimicrobial stewardship is defined (as previously presented
in Chapter 1) as ensuring that every provider selects “The
right antibiotic, for the right indication (right diagnosis),
the right patient, at the right time, with the right dose and
route, causing the least harm to the patient and future
TABLE 1
patients.” This definition outlines the key principles of antibiotic
Overview of Different outcome measures in antibiotic stewardship
prescribing. If followed strictly, these principles ensure that
providers only prescribe antibiotics for non-self-limiting bacterial From: Jan-Willem, et al. Expert Review of Anti-infective Therapy, 14:6,
569-575
infections. Figure 3 provides more detail to each principle as
relates it to clinical evaluation.
FIGURE 2
The goals of stewardship have been

outlined in Chapter 1: Introduction to AMR. This chapter will FIGURE 3
Principles of Prudent Antimicrobial
provide more detail to each of the five goals.
Prescribing

ANTIMICROBIAL STEWARDSHIP GOALS

Depending on the clinical setting AMS programs will target
their goals and outcomes based on available resources and
current short, mid and long-term opportunities. However, the
overarching goals fall under the following categories (Figure 4):
1) improve patient care and outcomes
2) reduce collateral damage and
3) impact costs.
FIGURE 4
From: Jan-Willem, et al. Expert Review of Anti-infective Therapy, 14:6, 569-575
IMPROVE PATIENT OUTCOMES

Antibiotics cause dysbiosis or disruption in the normally
“diverse” intestinal flora or gut microbiome.
One of the goals of antimicrobial stewardship is to
minimise or prevent unnecessary changes in the gut
biome to prevent the development and transmission of
antimicrobial resistance among our commensal biome.
Reducing antibiotic exposure will minimise the duration
and extend of disruption of the microbiome thereby
ultimately reducing collateral damage and improving
patient outcomes.
Antimicrobial stewardship programs have a direct
responsibility to ensure prudent antibiotic prescribing.
Multiple studies have shown that antibiotics are
prescribed unnecessarily in around one third to half of
the patients, and that they are prescribed inappropriately
(timing, molecule, dose, route, duration) in the same
FIGURE 5
proportions. Inadequate initiation of antibiotics can
Antibiotics Cause prolonged alterations to Gut Microbiome
increase mortality by up to 50%.

Inadequate therapy can refer to initiating therapy to which the There are many ways that a stewardship program may ensure
organism is resistant or initiating therapy with no coverage for timely and appropriate antibiotic initiation. One way is to create
the organism present (e.g. spectrum that is too narrow). clinical pathways that direct prescribers toward appropriate
antibiotics for specific disease states. These clinical pathways
can either be built into the medical record software at the time
of prescribing, or can be available to prescribers via a manual or
internet portal.
In addition to timely and appropriate antibiotic initiation,
stewardship programs may minimise risk for adverse events
by implementing interventions for timely review or renal dose
adjustment. Timely de-escalation (being part of the review of
antibiotic prescriptions) will minimize patient exposure to broad
spectrum antimicrobials and therefore reduce their risk for
associated events such as resistance or C. difficile infection.
Renal dose adjustments will ensure patients are not over- or
under-dosed which may increase their risk for adverse effects,
infection relapse, or development of resistance.
Surgical Prophylaxis
Antibiotic Stewardship programs may become involved with
FIGURE 6 standardising surgical prophylaxis to avoid unnecessary
Inadequate antibiotic therapy increases mortality
broad-spectrum antibiotic use and reduce rates of surgical site
infections (SSIs) using evidence-based therapies. Surgical site
In addition, prolonged courses of antibiotics increase the risk of infections are among the most common healthcare-associated
colonisation with multidrug resistant organisms. Therefore, the infections globally and have been associated with increased
chain of transmission (in particular within healthcare settings) post-operative hospital days, additional surgical procedures,
increases the risk of horizontally infecting more than one and often higher mortality. The 2014 Annual Epidemiological
patient. Interrupting the chain is as important as preventing the Report by the European Center for Disease Prevention and
development of resistance. Reducing unintended consequences Control (ECDC) reported that the cumulative incidence of SSIs
by practicing prudent prescribing and limiting the duration ranged from 0.5% up to 9.7%, with the highest rates in colon
of therapy to appropriate treat each infection with the safest, surgery (European Centre for Disease Prevention and Control.
effective course of antibiotics is an important stewardship goal. Annual epidemiological report 2014 Antimicrobial resistance
and healthcare-associated infections. 2015.). The ECDC has
published a systematic review and evidence-based guideline
on perioperative antibiotic prophylaxis (PAP) to standardize
administration, dosing, and duration of exposure
VIEW GUIDANCE DOCUMENT
Stewardship programs have an opportunity for intervention by

ensuring intuitions are following these guidelines to minimise
infections and patient exposure to unnecessary antibiotics.
Europe has seen a statistically significant decrease in surgical
site infections between 2009 and 2012 in the areas of cesarean
section (p<0.001) and laminectomy (p<0.01). Conversely, a
FIGURE 7 statistically significant increasing trend was noted for colorectal
Relationship between antibiotic use and duration of surgery (p < 0.05) (Figure 8).
Carbapenem Resistance colonization

FIGURE 8
Cumulative incidence of sergical site reported infections by year and operation type, EU/EAA, 2009-2012
TOOLKIT RESOURCE
Additional resources on antibiotic selection
based on surgical procedures have been
provided by the Society for Healthcare
Epidemiology of America (SHEA). (Anderson
DJ, Podgorny K, Berríos-Torres SI, Bratzler
DW, Dellinger EP, Greene L, Nyquist AC,
Saiman L, Yokoe DS, Maragakis LL, Kaye KS.
Strategies to prevent surgical site infections
in acute care hospitals: 2014 update. Infect
Control Hosp Epidemiol. 2014;35(6):605.)

LEARNING OUTCOME Lastly, comprehensive AMS programs would ensure access to

REDUCE COLLATERAL DAMAGE transitions of care services.
Reduce C. difficile colonisation or infection by controlling

“high risk” antibiotics. C. difficile is the leading cause of OPTIMISE HEALTHCARE COSTS
hospital-acquired gastrointestinal illness and has been Various types of antimicrobial stewardship interventions have
associated with increased length of stay, morbidity, and mortality. been published with associated cost savings. Table 1 shows
The most significant risk factors for C. difficile infection (CDI) a small sampling of some of these interventions. The most
are exposure to antibiotics and exposure to the organism. In common cost outcomes evaluated in stewardship studies
hospitals and long-term care facilities, C. difficile may be spread have included drug cost, laboratory costs, and length of stay.
on contact surfaces throughout the hospital and on the hands of These cost saving studies have been used to validate further
healthcare workers. Any antibiotic can cause CDI and investment into stewardship infrastructure and expansion.
is particularly important that we limit antibiotic use to the right
drug and duration to minimise alterations in the intestinal Study Intervention Impact
microbiome that allow C.difficile spores to germinate and Seligman SJ et al. Restriction Total reduction in
cause colonisation and infection. antibiotic costs by
29%
Britton HL et al. Clinical guidelines Total purchases
REDUCE ANTIBIOTIC CONSUMPTION AND of cephalosporins
COSTS WITHOUT INCREASING MORTALITY decreased by $55,715
or 46.2%
OR INFECTION-RELATED RE-ADMISSIONS
Briceland LL et al. De-escalation Total cost savings of
In order to reduce antibiotic consumption and costs without $38,920.95 during
increasing mortality or infection-related re-admissions, an intervention period
accurate diagnosis at the time of prescribing is key. AMS Avorn J et al. Clinical Pathway Savings of $76,000
programs may assist in accurate diagnosis by providing clinical annually
pathways which quickly summarise guidelines, or by ensuring McGregor JC et al. Computerized Savings of 84,188
monitoring software compared to control
access to rapid diagnostic options (e.g. rapid influenza or strep
arm over 3 months
tests). If positive, rapid influenza tests may decrease antibiotic
consumption as patient has a clear diagnosis of viral infection. TABLE 2
If negative, they may reduce anti-viral agent prescribing or Examples of documented cost savings associated with stewardship
inpatient isolation costs. interventions
Source : https://www.cdc.gov/getsmart/healthcare/evidence/asp-int-
Once a provider has determined that a patient truly has a costs.htm
non-self-limiting bacterial infection, an effort must be made to
choose the narrowest spectrum agent that is appropriate for More recently, a Cochrane review of 221 studies reviewed
the disease state. outcomes associated with AMS programs. In the review, duration
AMS programs may help providers by identifying infections with of antibiotic treatment decreased by 1.95 days (95% CI 2.22 to
the highest risk of over-prescribing and targeting those patient 1.67; 3318 participants; high-certainty evidence) with a similar
populations whether they practice in a clinic or ambulatory risk of death. There was also moderate-certainty evidence of a
healthcare setting, an acute care hospital or a long-term care decreased length of stay. Both of these outcomes directly impact
facility antimicrobial stewardship programs may also focus on overall healthcare costs and can be used to validate further
length of therapy to ensure that patients are treated for the efforts for AMS program expansion.
minimum duration supported by the literature.
TOOLKIT RESOURCE TOOLKIT RESOURCE

PDF ARTICLE SITE LINK
CDI IDSA Guidelines 2018 The full Cochrane review can be found here

LEARNING OUTCOME The potential of drug resistance to catapult us all back into a
EVALUATE CORE ELEMENTS OF world of premature death and chronic illness is all too real. As we
ANTIMICROBIAL STEWARDSHIP age and ponder the inevitable entry into the age demographic
AND DISCUSS OPPORTUNITIES TO in which our risk of hospitalisation is not negligible, it is worth us
IMPLEMENT CORE ELEMENTS IN YOUR thinking about how we might react to acquiring an infection with
PRACTICE SETTING carbapenemase-producing Klebsiella or a multidrug resistant
Pseudomonas for which there are no available antibiotics to use.
The U.S. Centers for Disease Control and Prevention have
established core elements necessary for developing a successful We must all recognise the seriousness of this problem and
antimicrobial stewardship program. These core elements are as commit ourselves to using these precious resources wisely. ASPs
follows: can help us identify such situations and avoid inappropriate
antimicrobial use. We have the means to
• Leadership Commitment: Dedicating necessary human,
ensure that our antimicrobial armoury remains effective
financial and information technology resources.
and that we preserve the effectiveness of future antimicrobials in
• Accountability: Appointing a single leader responsible for the pipeline.
program outcomes. Experience with successful programs
show that a physician leader is effective LEARNING OUTCOME
• Drug Expertise: Appointing a single pharmacist leader PATIENT CASES: APPLY KEY
responsible for working to improve antibiotic use. PRINCIPLES OF PRUDENT
ANTIMICROBIAL PRESCRIBING TO
• Action: Implementing at least one recommended action, THE FOLLOWING SCENARIOS
such as systemic evaluation of ongoing treatment need
after a set period of initial treatment (i.e. “antibiotic time 1. A 35-yo woman presents with 2 days of burning on urination
out” after 48 hours), IV to PO programs, prospective audit and today noticed some blood in her urine. You diagnose acute
and feedback, antibiotic restrictions, etc. uncomplicated cystitis. What is a 2010 IDSA Guideline first line
recommended agent for treatment of AUC?
• Tracking: Monitoring antibiotic prescribing and resistance
patterns a. No antibiotics and reassurance
b. Cranberry juice
• Reporting: Regular reporting information on antibiotic use
and resistance to doctors, nurses and relevant staff c. Ampicillin
d. Ciprofloxacin
• Education: Educating clinicians about resistance and
optimal prescribing e. Nitrofurantoin
It is extremely important that healthcare providers recognise ANSWER: E

the need for and the value of ASPs and support their existence First-line agents for acute uncomplicated cystitis include
in healthcare facilities. The optimal structure and components trimethoprim-sulfamethoxazole, nitrofurantoin, or fosfomycin.
of ASPs will vary according to the specific institution’s needs. Fluoroquinolones are reserved as second-line therapy due to
However, a successful program requires the involvement of well high prevalence of in-vitro resistance. Ensuring that patients
trained and enthusiastic physicians and pharmacists and the are started on the correct guideline-based therapy can prevent
strong support of the healthcare administration and medical staff. further fluoroquinolone resistance from developing due to
Interested physicians and pharmacists can usually demonstrate overuse with inappropriate prescribing.
to institutions that an ASP can pay for itself in short order by
reducing pharmacy costs and reducing length of stays.
In summary, we need to use our resources wisely; “to widen

access to appropriate medications to encompass all people –
regardless of race, gender, or socio-economic status – while at
the same time reserving these precious compounds to treat only
those diseases for which they are specifically required.”
Our grandparents lived during an age without antibiotics.

2. A 58-year-old female with end stage renal disease has fever the system. The following chart provides examples of possible
(Tmax 101.9 F) during hemodialysis. Three sets of blood cultures unintended consequences that should be tracked and reported
are taken and patient is empirically started on vancomycin and concurrently with the primary outcomes.
cefepime. At 72 hours cultures report a methicillin susceptible S.
aureus (MSSA). Using stewardship principles, what alterations in Stewardship Goals Possible Unintended
Consequences
antibiotic therapy should be recommended?
a. Discontinue cefepime and continue vancomycin Reducing length of stay Increasing rates of readmission
b. Discontinue cefepime and vancomycin, initiate cefazolin Reducing duration of surgical Increasing rates of surgical site
c. Discontinue cefepime and vancomycin, initiate ceftaroline prophylaxis infections
d. Replace the hemodialysis catheter and discontinue all Restricting or limiting specific Increasing use of non-restricted
antibiotics antimicrobials to reduce antimicrobials (e.g. "squeezing
inappropriate use the balloon")
ANSWER: B Delaying doses of antimicrobials
Beta-lactam antibiotics are preferred over vancomycin for due to restriction processes
treatment of MSSA. The appropriate course of action is to
discontinue antibiotics that are no longer necessary (e.g. SOURCE
cefepime for gram negative coverage), and de-escalate the http://www.idsociety.org/Guidelines/Patient_Care/IDSA_Practice_
vancomycin to a narrow-spectrum beta-lactam, such as cefazolin Guidelines/Antimicrobial_Agent_Use/Implementing_an_Antibiotic_
or oxacillin. Stewardship_Program/

SITE LINKS SITE LINKS
Alliance for the prudent use of antibiotics “APUA” Clinical Hughes J, Huo X, Falk L, Hurford A, Lan K, et al. (2017)
Scenarios “Test Target Treat" Benefits and unintended consequences of antimicrobial
de-escalation: Implications for stewardship programs.
Managed Healthcare: 4 Case Studies PLOS ONE 12(2): e0171218
Benefits and unintended consequences of antimicrobial

Stewardship Program Examples: US CDC de-escalation: Implications for stewardship programs
BSAC Gram Negative MOOC: Online course on

antimicrobial stewardship and management of Gram
negative Infections References:
1. Hassoun A, Huff MD, Asis E, Chahal K, Azarbal A, Lu S. Effect of
target-enriched multiplex polymerase chain reaction on patient
POSSIBLE UNINTENDED CONSEQUENCES outcomes and costs during the 2013-14 influenza season. J Hosp
OF ANTIMICROBIAL STEWARDSHIP Infect. 2017 Apr 21. pii: S0195-6701(17)30196-2).
The performance management of any stewardship program is 2. Bratzler DW, H. P., & Surgical Infection Prevention Guideline Writers
measured primarily through structural and process measures Workgroup. (2005). Antimicrobial prophylaxis for surgery: An advisory
with various measurable outcomes according to the literature. statement from the national surgicalinfection prevention project. Am J
Nonetheless, balancing measures to detect unintended negative Surg, 189(4), 395. doi:10.1016/j.amjsurg.2005.01.015).
consequences of these interventions are fundamental to ensure 3. Surveillance of surgical site infections in Europe 2010-2011. ECDC
that antibiotic stewardship programs are safe. Healthcare Surveillance Report. 2011.)
systems, clinicians and patients should be confident of the 4. Surawicz CM1, Brandt LJ, Binion DG, Ananthakrishnan AN, Curry SR,
results and value of the interventions. Gilligan PH, McFarland LV, Mellow M, Zuckerbraun BS. Guidelines for
Balancing measures (looking at a system from different diagnosis, treatment, and prevention of clostridium difficile infections.
directions) measure the effects of changes designed to improve Am J Gastroenterol. 2013;4(108):478.)
one part of the system causing new problems in other parts of

CHAPTER 4
AUTHOR: CONOR JAMIESON
KEY STEPS IN DEVELOPING

AN ANTIMICROBIAL
STEWARDSHIP PROGRAMME
LEARNING OUTCOMES
CHAPTER IS TO:
• Describe key steps in developing an antimicrobial stewardship programme
Identify a range of
• Identify the key personnel who need to be involved in the programme
stewardship activities that
• Outline some key activities to be carried out by the stewardship programme
are applicable to a broad range
of healthcare settings. • Describe some output measures that can be monitored for the programme
(financial, guideline compliance, outcomes - decreased length of stay, etc.)
Identify the key personnel who
need to be involved.
INTRODUCTION
Describe the developmental
The goals of antimicrobial stewardship and a range of definitions of stewardship were
stages in the processes.
outlined in Chapter 1. An antimicrobial stewardship programme is a systematic approach to
Outline some of the potential implement a range of activities to achieve those goals. These can be as basic or as complex
barriers to these stages and as resources allow - a range of relatively simple interventions can produce measurable
suggest solutions to changes in antimicrobial use, but if the ultimate aim is to drive improvements in the quality
overcome them. of prescribing with improved patient outcomes, then a mix of activities will be required,
involving a range of healthcare professionals.
A stewardship programme can only be successful in an organisation or healthcare setting if

the following criteria are met:
• Motivation to improve outcomes for patients with infections, prevent avoidable harm r
elated to antimicrobial prescribing and a recognition of the potential and actual impact
of antimicrobial resistance; this motivation needs to be present at many levels in an
organisation – both from healthcare professionals but also shared by the senior
executive team, those with the power to implement/support/fund the scheme, or capable
of being persuaded of the benefit of the scheme (whether in terms of the benefits listed
above, or purely financial/operational benefits);
• The stewardship programme is established with clear lines of accountability and

there is a structure within the organisation/setting that can allow the implementation of
a stewardship programme to take place, support the scheme, monitor its performance
and hold it to account for performance and outcome measures;

CHAPTER 4 - KEY STEPS IN DEVELOPING AN ANTIMICROBIAL STEWARDSHIP PROGRAMME
• There needs to be both clinical and executive leadership

provided to and by the scheme – it needs to have high level
support and input from a senior management team, as TOOLKIT RESOURCE
well as clinical supporters/champions. These are essential
to overcome any organisational and professional barriers that
SITE LINK
might hamper the activities of the programme. Sinai Health System – University Health
Network Antimicrobial Stewardship Program
The core components of a stewardship programme have been
(SHS-UHN ASP).
outlined by CDC and are listed below:
VIDEO
Sinai Health System – University Health
Network Antimicrobial Stewardship Program
(SHS-UHN ASP).
WATCH VIDEO
https://www.cdc.gov/getsmart/healthcare/implementation/core-elements.html
Identifying the need for an antimicrobial stewardship may come • High levels of antimicrobial consumption (and associated
from a number of drivers: costs), perhaps compared to relevant regional or national
benchmarks
• Local audit which identifies problems in clinical practice
(e.g. poor adherence to guidelines) • A need to implement a stewardship programme, driven by
local health regulators or other similar organisations having
• Poor patient outcomes, or evidence of avoidable harm
such a programme in place.
(e.g. high rates of surgical site infections, Clostridium
difficile infections)
• High resistance rates in pathogens of clinical significance

in the healthcare setting and the local environment

TOOLKIT RESOURCE
PDF ARTICLES
A sample antimicrobial stewardship
programme proposal
Development of a business case for an inpatient

Antimicrobial Stewardship Program
How to pitch an Antibiotic Stewardship Program

to the Hospital C-Suite
ARTICLE
Karanika et al. Systematic review and meta-
analysis of clinical and economic outcomes from
the implementation of hospital-based antimicrobial
stewardship programs. AAC, 2016; 60:4840-4852
BUSINESS CASE
SITE LINK
For the fortunate few, once the need has been identified, it
Pulcini et al, Commentary: Human resources
may be possible that there is funding and support identified to
estimates and funding for antibiotic stewardship
move onto the next step of setting up the programme, but for
teams are urgently needed, Clinical Microbiology
many settings it is likely that a business case for funding the
and Infection, https://doi.org/10.1016/j.
programme will be required. Those who control the budgets for
cmi.2017.07.013
funding initiatives like a stewardship programme may have to
be persuaded of the benefits of such a scheme, in the face of
competing priorities for funding.
In this context, there may be a number of metrics that are known ANTIMICROBIAL STEWARDSHIP
which can help support a business case for a stewardship COMMITTEE
programme: A stewardship committee is fundamental to any stewardship
scheme as it will provide the strategic direction, guidance,
Operational Financial Clinical
manpower, intelligence, resources etc. for any stewardship
Reduction in length Reduced No increase in
activities.
of stay for hospital expenditure on mortality
inpatients antimicrobials It may be a stand-alone group or it may be a sub-committee
No increase in ICU Reduced Reduced incidence or part of a larger group such as an infection prevention and
length of stay consumption of of infections due to control committee or a drugs and therapeutics committee. If it is
broad spectrum key multi-resistant a stand-alone group, it should be integrated into the governance
antibiotics organisms structure of the organisation so that it is accountable. The
diagram below outlines how such a committee might fit in a
This business case should outline any initial and ongoing hospital setting.
education and training requirements that might need to be
funded to further develop the individuals or staff groups
recruited/redeployed to stewardship activities – these could
include attending training days, courses or conferences.
Examples of how business cases may be developed are
provided in the resource box. Many examples stem from a US
perspective but could be adapted to geographical, healthcare
system and resource context.

Taken from BSAC ‘Practical Guide to Antimicrobial Stewardship in Hospitals’ by Dilip Nathwani and Jacqui Sneddon
Composition of a stewardship committee: Nurse Input from and representation

A successful committee will be one which includes of nursing staff; key staff
representatives of key staff groups involved in antimicrobial group who can have a major
prescribing, and which is representative of the organisation it impact on stewardship; often
is a part of. One of the biggest challenges for the committee provide patient’s perspective
will be getting the required members to attend, and the time
Junior doctor representative Insight from the ‘shop floor’
commitment from busy healthcare professionals should not be
of the organisation; liaison
underestimated. In primary care, it may be difficult to access the
with other junior medical staff;
specialist expertise that is usually available in secondary care,
feedback
such as infection specialists.
Pharmacy representative Additional insight from
Staff member Key Benefits/Rationale pharmacy staff
Medical microbiologist In depth microbiology Primary care representatives
knowledge, laboratory (for secondary care
knowledge, clinical committees
knowledge Secondary/tertiary care
Infectious diseases physician Clinical knowledge, infectious representatives (for primary
diseases knowledge care committees)
Antibiotic pharmacist In depth knowledge of Data analyst Support for data analysis, IT
antibiotics, PK/PD, formulary skills
maintenance, clinical
pharmacy knowledge Of these, there will be a core team of individuals who are
Infection control nurse Input into infection control involved in the day to day activities of implementing, delivering
agenda, liaison with Infection and monitoring the stewardship scheme. These usually include
Prevention and Control infectious disease physicians, medical microbiologists and
committee specialist pharmacists, in hospital settings, but the composition
of the core team may vary from one place to another.
Consultant physician and Clinical knowledge,
consultant surgeon representation of consultant
physician staff group, ‘shop
floor’ experience

Identifying the expertise Champions and supporters outside of the stewardship

It is likely that any organisation will already have some of the committee:
key members of a stewardship team in place, but it is also likely While it is important to have expertise within the group, it is
that there may be a need to recruit some expertise, or else also vital to have supporters and champions who will promote
train/up skill existing employees to take on or be involved in a and support the work of the group in the wider organisation. In
stewardship role. addition, the group should be able to promote the benefits of
its activities in terms of patient safety, reduced harm, reduced
Part of the remit of the group should be to recruit the experience
length of stay, reduced morbidity.
and expertise it needs to be able to deliver the remit outlined in
the terms of reference of the group, if this is not in place when Identifying priorities for the group:
the group is formed. Once a group has been formed and staffed/supported
appropriately, the next step is to develop an action plan for
In resource limited situations, it may not be possible to
the group – either surveying the organisation to identify key
access the expertise required to implement a fully developed
priorities, or using prior knowledge to identify the priorities for
antimicrobial stewardship programme in house; in these
the group.
situations, it may be necessary to rely on non-expert staff groups
to implement elements of a stewardship programme that are There are a number of potential indicators of problem areas or
practical and feasible (see chapter 16), sometimes within a areas needing intervention within an organisation or healthcare
distant mentorship programme. Even a limited stewardship setting, and the diagram below lists some, but is not exhaustive.
programme can bring benefits in terms of reducing antimicrobial
consumption.
High resistance in key

pathogens locally or
nationally
Poor knowledge of good
Critical incidents/patient
antimicrobial stewardship
safety issues
within the organisation
High incidence of
healthcare associated PROBLEM Expenditure
infections e.g. Clostridium AREAS - increasing costs
difficile infection
Antibimicrobial Outlier when

consumption benchmarking with similar
data - primary and organisations
Audit identifying
secondary care
poor practice

High resistance in key pathogens locally or nationally Once this has been done, develop an action plan to address
identified from resistance surveillance, local antibiograms, issues. The scale of the task may seem overwhelming, so
high use of broad spectrum agents, information from national might be best to tackle the easy wins first – for more complex
surveillance programmes. tasks, using quality improvement and implementation science
techniques see chapter 11. The table below provides examples
Critical incidents/patient safety issues
of stewardship activities that may be relevant, with an
organisation may have reporting system for patient safety
approximation of the timescales involved in implementing any
incidents; monitor for incidents relating to antimicrobial use;
activity and the level of input required to implement and maintain
audits of door to needle times for sepsis; high rate of surgical site
it going forward.
infections indicating poor practice in antimicrobial prophylaxis;
Morbidity and Mortality meetings, Root Cause Analysis of critical Timescale
incidents.
Level of Short Medium Long term
Outlier when benchmarking with similar organisations intervention
it may be possible in some countries to benchmark local Low Formulary Pre- or post- Controlling
performance with certain indicators to other similar restriction; authorisation access of new
organisations, or a national average Selective programmes antimicrobials
reporting of for restricted onto
Audit identifying poor practice
microbiology antibiotics formulary;
e.g. poor compliance with prescribing guidelines, poor patient
outcomes in specific infections (c.f. critical incidents); excessive results Dedicated
durations of antimicrobial therapy antibiotic
prescribing
Antimicrobial consumption
section on
evidence of increasing antimicrobial consumption; consumption
drug chart
higher than similar organisations or locations (c.f. benchmarking)
Medium to Guideline Audit Referral
High incidence of healthcare associated infections high development, programme systems
e.g. healthcare associated Clostridium difficile infections; surgical dissemination Audit and Resistance
site infections; outbreaks and feedback surveillance
Poor knowledge of antimicrobial stewardship guidelines implementation;
Dose Antimicrobial
perhaps do not exist in the organisation; poor compliance with Point optimisation/ consumption
guidelines identified from audit, stewardship rounds etc. prevalence PK-PD/ Behaviour
surveys; Therapeutic change
drug techniques;
monitoring
TOOLKIT RESOURCE service
Academic
detailing;
SITE LINKS Stewardship
rounds;
PHE Fingertips website
Education
ESAC Antimicrobial resistance data and training;
Quality
ECDC improvement
projects;
CDDEP Resistance map Computerised
decision
support in
electronic
prescribing
systems

DEVELOPING ANTIMICROBIAL EDUCATE AND TRAIN

PRESCRIBING GUIDELINES
Education is a key part of antimicrobial stewardship, but it
It is unusual for no guidance on antimicrobial prescribing to
can be extremely time consuming, especially when the sheer
be available to prescribers in most healthcare settings, but
number of healthcare professionals who need to be educated is
there will undoubtedly be some situations where this is the
considered.
case. In such situations, the time and effort required to develop
guidelines from scratch may be considerable, and it may be Developing educational resources can be challenging, especially
a more cost-effective initial step to borrow and adapt other in resource limited settings. In these situations, making use of
guidelines that are relevant to the local situation, or implement existing resources can be the most effective strategy.
national guidelines where these are available. These can then be Internet or web based educational resources [e-learning
modified to suit the local situation – for example, recommending resources] are likely to be the most cost-effective method of
appropriate drugs which are available locally and are included on reaching large groups of staff, where the infrastructure exists to
the local formulary. allow this – see the BSAC MOOCs on Antimicrobial Stewardship
Where this is done, it is important to sense check the guidelines and Gram-negative infections.
and ensure that local resistance profiles don’t undermine the
empiric recommendations.
Once this is done, there should be a plan to review these on a

regular basis to ensure that they remain relevant and current.
This article, published in 2002 provides a very good summary

of the steps involved in developing, disseminating and
implementing antibiotic guidelines.
Face to face education can be very effective, but consideration

must be given to the practicality of this – large groups of
VIEW GUIDELINES ARTICLE staff, time consuming to develop education and deliver it, and
frequently changing/rotating staff mean the task can seem
endless.
Opportunistic educational interventions can occur on

stewardship ward rounds and can be helpful in highlighting poor

TOOLKIT RESOURCE practice or reinforcing good practice, explaining a particular
learning point or putting knowledge into clinical context.
PDF ARTICLE A one size fits all model does not work when there are different
WHO guideline development article professional groups who need to be educated, or there are
differing levels of knowledge within a professional group.
SITE LINK
A Quick Win from India – The Impact of Policy

Guidelines on Hospital Antibiotic Use over a
Decade: A segmented time series analysis Chandy
TOOLKIT RESOURCE
et al, 2014 SITE LINKS
BSAC Antimicrobial Stewardship MOOC
Gram negative infections MOOC

Day to day activities: importance of having protected time to carry out antimicrobial
The core team involved in antimicrobial stewardship activities stewardship activities, something which should be addressed in
(see above) will probably do may of the following activities on a any business case.
daily basis:
Measuring success or progress:
• Providing consults for specific patients, at the request of Careful consideration should be given to how the achievement
clinicians – providing guidance on appropriate investigations of the priorities, or progress with achieving them, can be
and sampling, initiation of empiric therapy, streamlining measured. This should be planned from the very beginning.
to directed therapy, recommendations for referral to other
Questions to ask:
specialties for imaging, surgery or other investigations or
What does success look like – what are we trying to achieve? For
management;
example, reduction of empirical broad spectrum antibiotic use in
• Reviewing prescriptions for antimicrobial agents – checking a specific clinical area.
for appropriateness, guideline compliance, monitoring use of
How will success be identified? What will we measure to know
restricted agents or agents which require specific
that we have reduced this?
authorisation from ID or microbiology;
Does everyone know what we are trying to achieve, and why?
• Providing advice on optimisation of antimicrobial therapy –
Often we forget to involve front line staff in the understanding of
e.g. therapeutic drug monitoring for narrow therapeutic index
the need for change, and fail to take account of their needs and
agents, modifying doses in renal or hepatic impairment,
priorities when trying to implement change
advising on alternative therapy in cases of clinically significant
drug interactions with existing medication How long will it take to measure? How often do we need to
measure? Is our planned measurement process feasible, can it
• Promoting conversion from IV medication to oral options
be carried out within existing time constraints? Is the frequency
• Providing education – formal teaching session, ad hoc of measurement achievable?
education on ward rounds
How will we know if we have failed or if the change is causing
• Gathering data – e.g. point prevalence surveys, audit data, harm or increasing risk?
quality improvement data collection, primary care prescribing
For example, a policy change to switch from using
data
cephalosporins for surgical prophylaxis in orthopaedic surgery
• Maintenance and update of existing guidelines to using gentamicin led to a 94% increase in acute kidney injury
(AKI) in a Scottish hospital. Bell et al, JASN 2014;25:2625-2632
• Managing an outpatient parenteral antimicrobial therapy
service
• Academic detailing e.g. in primary care physician practices
• Horizon scanning – monitoring the availability of new

VIEW ARTICLE
antimicrobial agents and their impact on practice, financial
monitoring of expenditure on antimicrobials, assessment of
new evidence or national guidance on local practice; dealing
with drug shortages; reviewing local resistance profiles for
key pathogens;
• Implementing and monitoring compliance with national

quality standards or quality initiatives (e.g. CQUIN or Quality
Premium targets in UK, NSQHS3 in Australia, CMMS scheme
in USA).
For medical professionals, these activities will take place in the

context of a number of competing priorities including managing
individual patients under the ID team, running clinics, running the
clinical microbiology laboratory service, authorising microbiology
results and so on. For pharmacy professionals, they may also be
required to provide general clinical pharmacy services on wards
or in the pharmacy department. This serves to underline the

Within an antimicrobial stewardship programme, there is However, the table below illustrates how these barriers may
often a mix of measurement processes going on – continuous be overcome:
background monitoring of simple to collect data (often collated
Barriers Potential solution
by someone outside of the ASP team) such as financial
Lack of personnel/funding Use/train staff with broad
expenditure, volumes of antibiotics dispensed, length of stay –
skills sets e.g. align infection
as well as more targeted measurements of quality such as point
control and stewardship skill
prevalence surveys and localised quality improvement initiatives.
sets; develop a business case
Monitoring of local adverse incident reporting systems, where
to recruit staff.
they exist, is also important. Chapters 10 and 11 have more
detailed information on measuring antimicrobial use and quality. Educational challenges – BSAC MOOC (https://www.
limited teaching in medical futurelearn.com/courses/
Barriers: education; up-skilling antimicrobial-stewardship/),
In an ideal world, there would be sufficient resources available pharmacy and nursing staff online courses such as
to develop an antimicrobial stewardship programme in any given to be involved; sheer volume those for nursing staff (http://
healthcare setting, which would be welcomed by administrators of healthcare professionals www.nes.nhsscotland.com/
and clinicians alike, with full engagement with its various involved; access to education-and-training/
initiatives. In reality, there are always a number of barriers to educational events or courses by-theme-initiative/
implementing any programme and these vary depending on the for key staff healthcare-associated-
local situation. infections/training-resources/
A global survey of antimicrobial stewardship was conducted antimicrobial-stewardship-
in 2011, and it also gathered information on the barriers that workbook.aspx), pharmacy
prevent the implementation and delivery of antimicrobial staff (http://nwapg.co.uk);
stewardship programmes. The table below lists the most Health Education England
commonly reported barriers. (https://www.e-lfh.org.uk/
programmes/antimicrobial-
resistance/).
See chapter 13 for more
information on education
and competencies, including
examples from other
countries.
Geographic – multi-site, Using IT where possible –
on and off-site provision of electronic referral systems,
services, out of hours advice/ apps for mobile phones
information to access guidelines etc.
Howard et al. JAC 2015; 70: 1245-1255 Telecommunications can be
used to overcome geographic
barriers, and the increasing
availability of internet based
conferencing may be a
solution
Infrastructure – may be Look at low-tech solutions
basic/limited and may not be for providing advice or
opportunities to implement information; posters or
structural changes which leaflets in clinics or on wards;
could have a big impact – use of apps that don’t require
e.g. electronic prescribing, internet access
amending drug charts, no
internet or other IT systems

Getting buy-in from medical/ Promotion of benefits of

surgical staff, especially in scheme, including need for
areas where professional all healthcare professionals
boundaries are maintained to be involved; may need
and inter-professional working profession specific messages
is not established. and interventions; recruit
champions to help break
down professional barriers
https://bmchealthservres.
biomedcentral.com/
articles/10.1186/s12913-016-
1290-0
Resistance to getting project Sell the benefits – costs, bed

started days, outcomes; focus on
quick wins to build confidence
and support, such as monthly
spend for certain antibiotics
reducing as part of the
stewardship scheme.
Breaking down the view that Sell the benefits, and highlight
the stewardship team are the the threats; promote the
‘police’ and developing co- positive effect on patient
operative working to improve outcomes with lack of
patient care. evidence of harm where
appropriate; have a consistent
message that antibiotic
stewardship is about
improving prescribing, not
about restricting antibiotics or
reducing costs.
Working in areas where Up skill the existing staff
there is no clinical pharmacy groups to understand and
service, or no medical implement basic antimicrobial
microbiologists, or no ID stewardship initiatives; make
physicians; nursing staff use of staff with related
roles not evolved; no access skill sets; use regional
to microbiology services or and partnership models
results. for stewardship – see this
example from Denmark
http://qualitysafety.bmj.com/
content/22/11/907

CHAPTER 5
AUTHOR: PAUL POTTINGER
ASSESSING THE NEED

AND MOTIVATION
LEARNING OUTCOMES
CHAPTER IS TO: • Develop strategies for measuring the process and outcomes of your centre’s current
Learners will prepare to stewardship activities.
implement new antimicrobial • Clarify the organisational structure and accountability of your centre’s current
stewardship initiatives stewardship activities.
- either from scratch or • Explore and document your center’s motivation to improve antimicrobial stewardship
to add new features to in terms of its leadership and dedication to the cause (measured in human and
“
existing programs - by first financial capital).
understanding the current
state of affairs at their center.
The secret of change is
to focus all of your energy,
not on fighting the old,
but on building the new.
–Dan Millman
INTRODUCTION
Congratulations. If you’ve made it this far in the book, you understand the importance of
antimicrobial stewardship: It enhances individual patient outcomes and improves public
health. Antimicrobial stewardship is wonderful! But… you sense that your centre could be
doing more. Where to start?
Understanding the current state of affairs is essential. You may be surprised to learn
of good work that is already being done at your hospital or clinic. If so, wonderful! But
perhaps with a specific resource or structural modification, even more remarkable things
could be accomplished! Or, you may be disheartened to find that virtually no stewardship
program exists. If so, take heart: that is an opportunity for change, and you may be the
one to take the lead.
Many centres have stewardship efforts that

lie somewhere between these extremes.
+
HAVES
–
NEEDS

CHAPTER 5 - ASSESSING THE NEED AND MOTIVATION
RESOURCES interventions proposed—by any single individual. As a rough

start, one pharmacist should probably be hired for at least
The word “resources” is often used as a euphemism for “money.”
every hospital 500 beds. But, if the level of patient complexity
Certainly, funding is an important consideration. However, the
is high, this may be insufficient. Some estimates and funding
situation is more complicated. Think of resources as “human”
requirements have been recently suggested and provide helpful
and “technical.”
steer in relation to human resourcing.
Human Resources:
Antimicrobial stewardship starts with people: That is why it’s fun!
And… that is why it’s challenging. Technology is key, and some
processes can be automated, but impactful stewardship remains TOOLKIT RESOURCE
a handcrafted discipline. Thus, the most important feature of
PDF ARTICLE
your assessment will be identifying the key stakeholders and
understanding their needs and expectations. Human resources estimates and funding for
antibiotic stewardship teams are urgently needed
Other human resources should be assured. Microbiologists are

also important partners, and there should be a plan for robust
collaboration between stewardship and the clinical laboratory.
Micro lab directors can provide antibiotic resistance data,
guide providers at the point of care with savvy messaging, and
implement rapid diagnostic testing to facilitate prompt de-
escalation of empiric therapy. Nurses and Clinical Officers are
front-line partners in care, and may have a large impact upon the
success or failure of stewardship programs. Understanding their
needs and securing their partnership should be a top priority.
Information technology (IT) specialists abstract data, generate

reports, and build interfaces. These activities require expertise,
and asking the stewardship leaders to take this on may
"Pharmaceutical (296)" flickr photo by Doug Waldron negatively impact their productivity. Are these individuals
https://flickr.com/photos/dougww/2333670399 available for consultation on a regular basis? Do they have
shared under a Creative Commons (BY-SA) license financial and professional incentive to collaborate? Finally, is
there assistance for the stewards in arranging meetings,
Effective stewardship programs are led by pharmacists and tracking projects, and staying organised? Administrative
physicians, preferably in full partnership. Each leader’s time assistance can make all the difference between effective
should be protected for stewardship activities. This work stewardship and failure.
requires dedicated time and attention, and should never be
added to a full plate. The proper amount of protected time varies
by circumstance and setting. In large centres, stewardship may
be a full-time job, whereas in smaller hospitals a reduced fraction
of effort may be appropriate. The best stewards are clinically
active and visible to front-line providers; this earns trust and
paves the way for acceptance of their recommendations. But,
because clinical medicine requires tremendous time and energy,
these questions require clear answers: Will stewardship leaders
be paid for their time, or will they have to apply for grants to
support their wages? What other duties are expected?
The ideal ratio of stewards to patients is uncertain, and

likely depends on the setting (for example, inpatient versus
ambulatory). A finite number of charts can be reviewed—and

Technical Resources: LEADERSHIP STRUCTURE AND

The modern practice of medicine generates epic floods of data: ACCOUNTABILITY
prescriptions, laboratory results, imaging, vital signs… charts
If one word could encapsulate antimicrobial stewardship, it
bristle with information. This provides antimicrobial stewards
would probably be “teamwork,” because so many stakeholders
with rich opportunities to support decisions in real time, mine
are involved. Partnership between pharmacist and physician
data, and understand trends. But, only if they have access to the
leaders is essential, and both should understand their roles and
information.
responsibilities from the beginning. For instance, if the physician
thinks of the pharmacist as an “assistant” or subordinate,
then the pharmacist’s job satisfaction may be reduced. If the
pharmacist expects the physician to review every intervention,
then progress may be painfully slow. This relationship should be
structured in the most equitable and efficient way possible.
How will the stewardship program fit into existing leadership

structures? Will the stewards be nested within the infection
prevention team, or will they be considered a separate entity?
Will they be held accountable for their work, and if so, what
criteria will be used to determine accountability? Hospital
executives are important stakeholders, but because stewardship
touches so many lives in so many ways, it may be difficult for
non-clinicians to grasp the program’s tremendous importance.
The pharmacist and physician stewardship leaders should
know precisely what their supervisors want and expect to
"Health and Medical Cloud" flickr photo by perspec_photo88
hear regarding progress and impact. How often will reports be
https://flickr.com/photos/111692634@N04/15855652400
shared under a Creative Commons (BY-SA) license required, what form should they take, and what information
should they contain? Executive sponsors need to know that they
are getting a good return on their investment, so they may focus
Does your centre embrace computerised order entry? Is the
on cost savings as measured by pharmacy expenditure, days of
medical record electronic, and if so is it searchable? Is the
therapy, and length of stay. These are fine metrics, as described
pharmacy database online, and if so can reports be generated
below… although tracking them can be a chore. If arbitrary goals
which facilitate tracking antibiotic use? If so, does it track
are set, the stewards should know what the implications are if
antibiotic orders or actual administrations, for instance via
they are missed.
patient barcode administration? Is there a system to alert the
stewards in real time if restricted medications are prescribed? If
the electronic medical record is a mosaic of different systems,
can it be tamed by a third-party solution—and, if so, is there a
commitment from the executive sponsors to pay for it, and from
the IT department to support it? These technical resources do
not surpass the human factors outlined above, but they can
make the steward’s job much easier if they are available. If these
resources are not available, work can still proceed at a slower
pace, but they may be worth negotiating for as part of a startup
package, or may become a longer-term goal to aim for.

Taken from BSAC ‘Practical Guide to Antimicrobial Stewardship in Hospitals’ by Dilip Nathwani and Jacqui Sneddon
PROCESS especially regarding de-escalation or dose adjustments. If so,

how will these cases be identified? When will the stewards
If stewardship efforts are already underway, you must
discuss them internally, and when will they reach out to the
understand how the program currently operates.
primary teams with recommendations?
Most programs employ a combination of prospective audit

with feedback and formulary restriction. Regardless of the
balance between these techniques, how is the stewards’ advice
communicated and recorded? Written recommendations may
improve recommendation acceptance, but getting those notes
into the chart takes time. Is this feasible in every case, or in
select clinical circumstances?
If a separate infectious diseases consultant practices in the

hospital, is that person informed of recommendations being
made by the stewardship team, to ensure a coordinated effort
and consistent messaging?
When does stewardship happen? Do protocols differ overnight,

on weekends, or during holidays? If so, what arrangements are
"doctor-researching" flickr photo by Tayloright made? If trainees cover these duties, have they been properly
https://flickr.com/photos/141311777@N02/26912273309 trained and are they able to obtain support when needed?
shared under a Creative Commons (BY) license
Finally, how are periodic outcomes reviews accommodated in
light of the very busy daily workflow (see below)? Is time allotted
One daily activity model emphasises formulary restriction, in for data abstraction, analysis, and presentation? How often will
which orders for certain “high value” antimicrobials require the team update order sets? When will new antimicrobial agents
stewardship approval. This approach has been demonstrated be reviewed for consideration of addition to the formulary? Are
to reduce inappropriate antimicrobial prescribing. But, if this is a educational efforts scheduled on a regular basis?
prominent feature of the program, who will field the calls?
A common alternative to formulary restriction involves

prospective audit and feedback. Here, prescribers may write
for high-value antimicrobials, but as clinical data accrues in
the coming days the stewards will reach out to guide them,

OUTCOMES Antimicrobial Resistance

Reducing, or at least delaying, the emergence of antimicrobial
Successful antimicrobial stewardship programs measure the
resistance is a key goal of stewardship efforts. Can your program
impact of their interventions in a variety of ways. Ask how the
demonstrate stability—if not improvement—in resistance rates
stewards know whether they are doing a good job. A range
for key pathogens over time? Patience is a virtue here, because
of outcome metrics have been recommended to evaluate
the antibiogram tends to change slowly, and because many
stewardship programmes.
specimens are collected at the time of admission, when the
microbial ecology may already be influenced by outside selective
pressures. But, this is an important yardstick to follow.
Guideline Compliance
If the stewardship team has published guidelines for
antimicrobial use, or created order sets for common
infections, how frequently are they being followed? And,
are there actionable trends regarding guideline compliance?
For instance, if a particular service rarely adheres to the
guidelines, have they been consulted to determine the issue
at hand? A related metric is time to effective therapy: How
long does it take teams to get their septic patients onto the
appropriate antimicrobial spectrum? Do patients with S. aureus
bacteremia always receive the bundle of best practices such as
undergoing echocardiography? Are providers willing to convert
from IV to PO route of administration when appropriate?
"Antibiotic Drugs" flickr photo by theglobalpanorama
https://flickr.com/photos/121483302@N02/14200527505 Clostridium Difficile Rates
shared under a Creative Commons (BY-SA) license
C. diff is a bacterium that may cause serious infection during
or after antimicrobial therapy. Virtually any antibiotic may
Common metrics include: precipitate C. diff infection, but risk rises with duration of
Antimicrobial consumption therapy and breadth of spectrum. And, it causes misery—if
Pharmacy expenditures are easily tracked, and management not true peril—for everyone involved. Thus, whether fair or
considers this an important number to follow. But, cost is only not, its incidence is frequently interpreted as a surrogate for
one measurement of antimicrobial consumption, and it may stewardship effectiveness.
not tell the whole story. For instance, if a few patients have Harm Avoidance
appropriately received long courses of expensive drugs, then Studying bad outcomes that do not happen is a stiff challenge.
it may not have been possible to cut the budget safely. And C. difficile infection, mentioned above, is one example of patient
antimicrobial expenses should be compared with the total harm. Other adverse events that can be prevented with vigilance
pharmacy budget over time. Tracking actual antibiotic orders include nephrotoxicity or ototoxicity due to aminoglycosides,
may be more illuminating. Measuring days of therapy (DOT) is central venous catheter complications among patients who
quite popular, because of ease of measurement: Every day that a might have received oral therapy, and serious drug-drug
patient spends in the hospital and receives even a single dose of interactions. Even one of these events will harm the patient
the drug in question is considered a day of therapy. This metric and place the hospital at risk. Effective antimicrobial stewards
does not distinguish between single doses (for instance if given warn frontline providers about these possibilities and offer risk
for surgical prophylaxis) and treatment doses. Thus, another reduction strategies. And, the stewards should be given credit
metric can also be used: The defined daily dose (DDD) which is for preventing these events.
the assumed average maintenance dose per day for a drug used
for its main indication in adults. The DDD allows for standardized
comparisons across centers, health systems, or entire nations.
However, some hospital pharmacy systems may not provide this TOOLKIT RESOURCE
information easily, thus making DOT an attractive alternative. PDF ARTICLE
Metrics

MOTIVATION
Ultimately, your needs assessment should yield a measurement
of the center’s eagerness to embrace change. Along with
leadership, the creation of stewardship structures, and good
communication, motivation is pivotal to driving change. The
greatest measure of motivation is a demonstrated commitment
to effective antimicrobial stewardship. A hospital lacking the
essential components above may still be fully committed to
revving up stewardship, but there should be evidence for this
commitment—both tangible and intangible.
"Businessmen shaking hands" flickr photo by reynermedia

https://flickr.com/photos/89228431@N06/11220931254
shared under a Creative Commons (BY) license
Intangible Commitment
Equally important—if not more so—is evidence that your efforts
will be welcome. This information may seem difficult to obtain,
but it is worth pursuing. The easiest way forward is to talk
with people… lots of people. Physicians, pharmacists, nurses,
Tangible Commitment
microbiologists, IT specialists, executives… all the stakeholders
A written document such as a charter or declaration of intent
who would be impacted by your work should be consulted. Is
should be agreed upon. This serves two purposes. First, it
this the first time stewardship is being organized at the center?
clarifies important details of the program, especially the financial
If so, is there a groundswell of interest and enthusiasm among
and logistical support for stewardship personnel. Second, it
frontline providers? Or, is this seen as a “top-down” initiative that
signals to everyone in the organization that leadership takes
threatens physician autonomy? Has stewardship been attempted
stewardship seriously. A public vote of confidence may be
there before? If so, what went wrong? Do healthcare workers
important for the new team in winning the hearts and minds of
already have an unfavorable opinion of stewards? Regardless
reluctant front-line providers.
of the backstory, pursuing intangible factors involves friendly
dialogue with stakeholders, which sets the stage for successful
implementation and long lasting collaborations.
CONCLUSION
In this chapter we have learned the importance of assessment—
assessment of the centre’s antimicrobial stewardship needs,
and its commitment to make change. This is essential to
accomplish before beginning the implementation of a new
program. Antimicrobial stewardship is serious business, and it is
challenging. If it were easy, everyone would do it! Invest the time
necessary to create a program that is impactful, sustainable, and
fun to direct.

DELIVERABLE: ASSESSMENT REPORT

ASSEMBLE A REPORT INCLUDING THE
FOLLOWING ELEMENTS:
Resources
• Team members (Is there a physician director, pharmacist director, microbiologist,
data analyst, administrative supporter?)
• Information technology (Is there infrastructure to obtain microbiological and medication
data in a timely fashion, and to generate summative reports as necessary?)
• Frontline provider support (Are order sets embedded in computer-order-entry, or within
easy reach of manual order entry? Is there protected time for ongoing provider education?)
Leadership Structure and Accountability

• Team member support (Executive championship to advocate for new resources?)
• Reporting structure (Clarity regarding expectations and timeline?)
Process
• Daily work flow (Prospective audit with feedback? Formulary restriction?)
• Committee involvement (Active participation in stakeholder groups such as infection
control, order set development, pharmacy & therapeutics?)
• Periodic reporting (Access to aggregate data periodically to assess progress?)
Outcomes
• Antimicrobial use (DOT or DDD measured?)
• Antimicrobial cost (Medications ordered, or administered, or purchased?)
• Antimicrobial resistance (Tracking changes to susceptibility of major pathogens to
representative classes of antimicrobials over time?)
• Compliance (Provide use of empiric guidelines, willingness to accept ASP recommendations?)
• Safety (Harm avoidance measured?)
Commitment
• Recognition of importance of ASP (Written charter or program declaration?)
• Financial support (Salary guaranteed for at least several years regardless of short-term
outcome measurements?)
• Groundswell of enthusiasm (General enthusiasm for ASP or palpable resistance?)

SUMMARY OF LEARNING OUTCOMES

TOOLKIT RESOURCE 1. Develop strategies for measuring the process and outcomes
of your centre’s current stewardship activities.
SITE LINK
2. Clarify the organisational structure and accountability of your
Barlam TF et al. Implementing an Antibiotic
centre’s current stewardship activities.
Stewardship Program: Guidelines by the Infectious
Diseases Society of America and the Society for 3. Explore and document your center’s motivation to improve
Healthcare Epidemiology of America. Clinical antimicrobial stewardship in terms of its leadership and
Infectious Diseases, Volume 62, Issue 10, 15 May dedication to the cause (measured in human and
2016, Pages e51–e77, financial capital).
National Quality Partners Playbook: Antibiotic

Stewardship in Acute Care. National Quality Forum,
National Quality Partners, Antibiotic Stewardship
Action Team. (2016)
CDC Antimicrobial Stewardship Implementation

Resources.
ARTICLE
Cosgrove SE et al. Guidance for the knowledge
and skills required for antimicrobial stewardship
leaders. Infection Control and Hospital
Epidemiology. 35(12): 1444-1451. (2014)
PDF ARTICLE
Jump Start Stewardship Implementing Stewardship

in a Small, Rural Hospital. (2016)
Measuring the impact of antimicrobial stewardship

programs Dik et al

CHAPTER 6
AUTHORS: RAHEELAH AHMAD & ALISON HOLMES
EXPERTISE, STRUCTURES
AND ORGANISATION
traditional, alternative and innovative
THE AIM OF THIS
CHAPTER IS TO: models for enhanced and broad
Be able to critically
analyse the structure and
clinical engagement in stewardship
organisation of antimicrobial
stewardship programmes
at the organisational and LEARNING OUTCOMES
national level for improved On completion of this chapter, the participant should be able to:
implementation. While this • Map within their own organisation where Antimicrobial Stewardship (AMS) programmes
chapter will be of interest to are situated
all readers, AMS pharmacists,
• Identify the concepts of expertise, structures and organisation in the national context
AMS committees where they
(using their country national action plan) and reflect on how this may help or hinder broad
exist, and local authority level
clinical engagement
managers who are planning
new programmes will find this • Understand the different ways in which other countries are involving professional groups
of particular interest. in the delivery of AMS programmes
• Take a view across the healthcare sector and reflect on a framework to assess the level
of integration of approaches to AMS
DEFINING YOUR ORGANISATION AND HEALTHCARE SECTOR

Health care is organised differently between countries and sometimes within countries (for
example federal and state level care). But the way health care is organised has implications
for the way AMS is organised, financed and monitored and hence on outcomes. As you
work through this chapter a series of short activities is recommended so that the concepts
remain relevant to your context. You may need to look at other resources or talk to others
within or outside of your organisation to fill in the gaps once you have had a go. When we
talk about the concepts of structures (what goes into a system) and processes (what we do
with these inputs) it is useful to look at these structures in some detail, how programmes
are formally organised and also the expertise available. Understanding and critiquing some
of the facilitators for and barriers hindering AMS improvement through the way AMS is
organised can help move away all the focus from individual behaviour change. This is not to
say that individual behaviour change is not important or effective, but if we pause and look
at structures and organisation this should then provide another mechanism for enhanced
behaviours, optimal clinical practice and patient experience.

CHAPTER 6 - EXPERTISE, STRUCTURES AND ORGANISATION
Activity A: Consider briefly the type of service organisation Activity B: Now complete the table below, again for your
you work within including where your patients come from, own healthcare organisation. If you are not based in one
if they can access you directly or must be referred. Are you single organisation then select one that you have working
described as a primary care, secondary, acute care (or other) knowledge of.
organisation? Thinking very broadly do these factors have
any implications for the way AMS is organised within
your organisation?
Finances come from Staff are deployed from Accountability

for AMS outcomes
Federal level
State level
Locally (at the level of

organisation)
Add here any exceptions –

so if it’s different for certain
professional groups or certain
indicators add it here
Activity C: Reflecting on the descriptions in activity A and B SITUATING ANTIMICROBIAL STEWARDSHIP

which (if any) in your experience have acted as facilitators for WITHIN THE ORGANISATION
improving AMS or indeed barriers? Are there any mis-matches in
This section looks at how AMS programmes are placed within
terms of lines of accountability which hinder effective AMS?
the organisation. Is AMS and Infection Prevention and Control
(IPC) integrated? Does AMS come under the umbrella of patient
safety or quality improvement? Understanding where AMS
programmes are positioned within the organisational structural
and process charts helps understand how performance of AMS
is captured (which is picked up in chapters 10 and 12). Two
examples are provided below (Figure 1 & 2).
The distinction between AMS, IPC and quality improvement is

historical in many cases. Though many of the desired outcomes
are consistent across these three functions they sometimes
appear as dis-jointed and distinct because of the way they are
organised. Simply by examining the structure and organisation
in your organisation can open up a conversation with colleagues
about aims of programmes. Whilst these programmes may be
aligned at strategic level, this alignment does not always transfer
to the day to day operational life of the organisation.
(Figures 1 & 2)

FIGURE 1
Example governance structure
FIGURE 2
Example organisational structure

EXAMINING WORKFORCE ENGAGEMENT

NATIONAL ACTION PLANS
ACROSS PROFESSIONAL GROUPS
Many countries are in the process of developing National Action
On the specific aim of assuring wider workforce engagement,
Plans. Those countries which have a strategy in place will be
there are limited published examples and almost all are from
thinking about execution and implementation. The next activity
higher income countries. This does not mean that such models
asks you to extend the assessments made above to your own
do not exist in low and middle income countries, but that they
national action plan. Readers are encouraged to also look at
have not been shared in the international literature. Assessing
plans of countries which are of contextual relevance due to
the extent of workforce engagement is particularly relevant when
health system organisation, culture, epidemiology, policy or
planning new programmes or expanding existing programmes.
another factor which may be comparable.
Two examples of such an assessment are provided below (Table
Activity D: The following link provides the library of National 1). Engagement is considered in two main domains. For a given
Action Plans programme: Who is the target audience? Who is involved in
http://www.who.int/antimicrobial-resistance/national-action- the delivery of the programme? The issue of roles of the wider
plans/library/en/ workforce are also discussed in chapter 25 and 26
Do these plans (your own country and one other selection as

suggested above) propose alternative and innovative models for
stewardship? Do they promote broad clinical engagement? Do
they suggest how this can be done? How?
TARGET Primary care Nurses Community Long-term Hospital Public health Public/ Other
Antibiotics clinician pharmacy institutional staff body patients
toolkit, care
England 6
Who is
the target
✓ ✓ Royal
College of
audience General
Practitioners
Who is
involved in
✓ ✓ ✓*
the delivery
of the
programme
* microbiologists, pharmacists
TABLE 1
Target and delivery of AMS initiative
TOWARDS INTEGRATED MODELS OF AMS has concentrated in hospital settings. This has been a helpful
and practical place to start but the hospital physical structure
Looking back at section one of this chapter where you were
is something of an ‘artificial’ boundary, which neglects bi-
asked about the part of the health sector in which you work
directional influences between hospital and community care
and at how the organisation may act as a barrier or facilitator,
services. Antimicrobial use in the community and long-term
we now look at using a more comprehensive framework for this
care facilities are associated with the development of AMR in
assessment. Healthcare organisations are composite parts of
and outside hospitals3. The way people access health care
health systems which are required to deliver best outcomes
varies in different countries and has evolved. For example, the
efficiently, whilst facing the challenges of macroeconomic
availability of blended care and complex patient care pathways
constraints, technology costs, and increasing public need and
in some countries allows for care which would traditionally have
demand. Models which achieve integration of care across
been delivered in hospitals to now be carried out on a day case
primary, secondary, tertiary and long-term care are needed to
basis as well as in primary and community care or in the
achieve this and particularly for AMS1 2. Much AMS activity

patient’s home. This evolution is both patient-centred and allows So how can we assess integration of AMS across services and
for more rational use of services. But with this comes the need sectors? The general healthcare literature offers a number of
for AMS approaches which are truly integrated across service theoretical integrated care models, however, AMS is not explicit
providers and sectors. The availability of antimicrobials without in any of these wider health system integration models.
a prescription in some countries, and increasing availability of
Using a model first developed for looking at programmes to
online pharmacies transcending country boundaries provides an
address infectious diseases (Malaria, TB and HIV), Table 2 sets
additional challenge for AMS 4. Fundamentally, AMS is lagging
out a comprehensive framework based on the six facets of
behind the advances made in health service delivery and patient
critical health system function 5. This framework can be used to
behaviours by remaining sector-based. It is even important that
assess the extent of integration and identify potential strengths
where resources are scarce the approaches suggested here
and weaknesses of multi-sectoral AMS.
for integrated models of care be considered at planning stages.
So it’s really important to think about integration NOW whether
planning or evaluating your AMS programme or initiative.
Facets of critical health systems function Elements of integration adapted for AMS initiatives
Stewardship and governance Regulatory mechanism
Accountability framework
Financing Pooling of funds
Provider payment methods
Funding source
Cross-programme use of funds
Planning Planning
Service delivery Human resources for delivery of AMS
Physical infrastructure for laboratory testing
Monitoring and evaluation Data collection and recording
Data analysis
Reporting systems
Performance management system
Demand generation Financial incentives
Information, education and communication
Definition of full and partial integration:
An element is classed as fully or predominantly integrated (green) across the health system if it is exclusively under the
management and control of the general healthcare system. An element is classed as partially integrated (amber) if some but not all
cases are managed and controlled both by the general healthcare system and a specific programme-related structure. A dimension
is not integrated if it is exclusively under the management and control of a specific programme-related structure (which is distinct
from the general healthcare system).
Extension activity E: This activity is recommended for the AMS

(or equivalent) committee or working group at organisational or
regional level. Using a RAG rating (red - not integrated; amber TOOLKIT RESOURCE
- partially integrated; green - fully integrated) assess the extent
EXCEL DOCUMENT
to which your programme is integrated using the definitions
provided in above Table 2 ). You may like to refer to the worked examples in the
literature or use the template provided here

CHAPTER 7
AUTHOR: NICK BROWN
THE ROLE OF LABORATORY

AND RAPID DIAGNOSTICS/
BIO-MARKERS IN
STEWARDSHIP
LEARNING OUTCOMES
CHAPTER IS TO:
• Explain what empirical prescribing is and understand why it is currently part of normal
Define empirical day-to-day practice.
antimicrobial prescribing
• Understand why empirical prescribing is not ideal and why improvement in the diagnosis
and discuss its limitations.
of infection are needed
Describe the core reasons • Explain how the laboratory can support antimicrobial stewardship activities
for why it is used.
• Explain why the clinician needs to understand optimal use of diagnostic tests and how
Review the time points in the the results could otherwise be misleading
patient’s overall treatment • Understand what rapid bio-marker tests are (e.g. C-reactive protein and procalcitonin)
where diagnostic test results
and how their use could help support antimicrobial prescribing decisions
can lead to interventions to
improve antimicrobial therapy.
Describe how the laboratory INTRODUCTION TO EMPIRICAL PRESCRIBING

can contribute to antimicrobial
In most healthcare settings, and especially in the community, the majority of people with
stewardship initiatives.
infections are treated without the use of any diagnostic tests. That is, a clinical diagnosis
Introduce some newer is made using the patient history and physical examination and a treatment, which may
technologies within the include an antimicrobial agent, is prescribed on the basis of a clinical judgement as to
laboratory and show how they the cause of the infection and what treatment it will respond to. Thus, a mild purulent
are changing the way in which skin infection is assumed to be most likely either staphylococcal or streptococcal and an
diagnostic tests are performed. appropriate antibiotic, such as flucloxacillin, or similar, is prescribed. This is empirical, or
‘best guess’ prescribing.
Describe the critical role of the
clinician in making best use of For many decades, such practice has worked well and this is particularly the case where
diagnostic tests. the clinical diagnosis is easy and reliable and susceptibility to the prescribed antimicrobial
agents is very high. Clearly, it is the only practical option where there is no easy access
Describe acute phase
proteins as bio-markers for to laboratory tests or where the costs of testing are not affordable. However, response to
infection and their use in empirical treatment cannot be guaranteed. Key risks associated with this practice include:

CHAPTER 7 - THE ROLE OF LABORATORY AND RAPID DIAGNOSTICS/BIO-MARKERS IN STEWARDSHIP
PRESCRIPTION OF ANTIBIOTICS
OVER- OR UNNECESSARY TREATMENT
WITHOUT KNOWING WHAT ORGANISM
OF CONDITIONS WHERE THE CLINICAL
IS CAUSING THE INFECTION,
FEATURES OF BACTERIAL AND VIRAL
LEADING TO UNNECESSARILY BROAD
INFECTIONS ARE SIMILAR (E.G. SORE
SPECTRUM TREATMENT TO COVER ALL
THROAT, COUGH, EXACERBATIONS OF
POSSIBILITIES AND A LIKELIHOOD OF
CHRONIC OBSTRUCTIVE PULMONARY
TREATMENT FAILURE IF THE WRONG
DISEASE, OTITIS MEDIA)
ORGANISM IS TARGETED
PRESCRIPTION OF ANTIBIOTICS
WITHOUT KNOWING WHETHER-OR- INCREASED LIKELIHOOD THAT THE
NOT THE ORGANISM CAUSING THE PATIENT WILL RETURN FOR ANOTHER
INFECTION IS SENSITIVE OR RESISTANT CONSULTATION AND A FURTHER
TO THAT ANTIBIOTIC WITH AN EVER EMPIRICAL ANTIBIOTIC PRESCRIPTION
INCREASING RISK THAT IT WILL BE GIVEN
IS RESISTANT
Therefore, it is possible that some patients with persistent such as those using the polymerase chain reaction (PCR), are
or recurrent infections could be treated with repeated more useful for viral infections than bacterial infections, although
courses of antibiotics without the prescriber ever having this is changing. Therefore, even in hospital, most antibiotic
a confirmed diagnosis. prescribing remains empirical. It is more likely in hospital than
in the community that a confirmed diagnosis will be made
The situation is slightly different for hospital in-patients, in that
eventually, even if this takes several days, but this is too late to
there is easier access to laboratory diagnostic tests. A patient
influence the initial antibiotic prescription.
with a suspected infection is more likely to have a range of
tests performed and these will include general investigations The issue of empiric antibiotic prescribing was a major
(such as blood count, electrolytes) as well as specific tests component of the report from the recent UK Antimicrobial
to diagnose the cause of infection (for example, by culture of Resistance (AMR) Review, chaired by Lord O’Neill. Here, one
urine in suspected cystitis, or blood cultures in the more unwell recommendation was that diagnostic tests should be developed
patient with suspected sepsis). Indeed, it has been stated that to enable the correct treatment to be moved earlier in the
approximately 70% clinical diagnoses in hospital are made on patient pathway and ultimately aim for a situation where the
the basis of a pathology test. However, the turnaround time initial prescription is an informed prescription. That is, treatment
for most of these specific tests is too long to be of immediate of what the patient has, rather than what they might have.
practical help for the clinician and this is because most tests Some of the tests we need to achieve this would be described
for bacterial infection still rely on prolonged incubation to grow as disruptive technologies. This term is used to describe new
bacteria on culture media. Serological tests rely on the detection developments that require a new way of thinking about or
of antibodies to the infection and these may not appear for at managing a process.
least 10-14 days after the onset of the infection. Molecular tests,

A variety of different initiatives have been launched to help

facilitate this. The Longitude Prize is a £10m prize fund that will
reward the development of a rapid, affordable and easy to use TOOLKIT RESOURCE
point-of-care (point-of-care) diagnostic test that will help improve
SITE LINK
the immediate diagnosis of infection (and thereby conserve
antibiotics and reduce the selection pressure on the emergence Rapid diagnostics: stopping unnecessary use of
and spread of resistance) (https://longitudeprize.org/). antibiotics. The Review on Antimicrobial Resistance.
Chaired by Jim O’Neill. October 2015.
https://amr-review.org/
THE USE OF CURRENTLY AVAILABLE
DIAGNOSTIC TESTS TO INFORM THE
OPTIMAL USE OF ANTIBIOTICS The complete review is made up of several reports, many of
which will be of interest to the participant. However, here we
While initiatives such as the O’Neill review will influence concentrate particularly on the report relating to the use of
the development of new diagnostic tests, even now, various diagnostic tests:
laboratory methodological strategies to improve the utility
of current tests have been, or are being introduced.
The laboratory can have a key role in the identification and
PDF ARTICLE
management of patients with infection and therefore help This report provides an overview of how diagnostics
guide antimicrobial prescribing. This can facilitate antibiotic can play an important role in the fight against
stewardship initiatives at a number of different time points in antimicrobial resistance, by reducing unnecessary
the patient management pathway. use. It addresses how we can improve innovation as
well as encourage the uptake of diagnostics.
Initial patient consultation
Diagnostic tests can be valuable to help rule in or rule out

PDF ARTICLE
the presence of an infection at the first point of contact with A Pluddemann, I Onakpoya, S Harrison, B Shinkins,
a clinician. Ruling out infection may be as useful, and B Shinkins, A Tompson, R Davis, CP Price and C
sometimes more useful, than ruling it in. Tests with a high Heneghan. Position Paper on Anti-Microbial Resistance
negative predictive value can be used to identify patients Diagnostics – Centre for Evidence-Based Medicine,
who do not need treatment with an antibiotic or who may University of Oxford June 2015.
be suitable for a delayed treatment prescription. An example
would be the use of a urine dipstick test in a young woman
with symptoms of possible urinary tract infection, but who
was not particularly unwell.
Antibiotic treatment review at 48-72 hours
The ability to distinguish between viral and bacterial infection
is also useful, since patients with viral infections may be able If diagnostic tests are performed at the time of the initial
to be managed without antibiotics. An example would be the presentation of the patient, it is likely that results will begin to
use of point-of-care molecular tests for respiratory tract be available after 48-72 hours, depending on the investigations
viruses, such as influenza, respiratory syncytial virus (RSV) performed. While this is too late to alter the immediate treatment,
and rhinovirus. it does offer the opportunity for the treatment to be reviewed
and amended as appropriate. This is the basis for the ‘Start
Ideally, diagnostic tests used in this situation should have a Smart then Focus’ strategy promoted in the UK (https://www.
very quick turnaround time (optimally available at point-of-care), gov.uk/government/uploads/system/uploads/attachment_data/
since a result is needed in a very short time frame to be able to file/417032/Start_Smart_Then_Focus_FINAL.PDF). The initiation
influence the immediate treatment decision. However, currently, of prompt antibiotic therapy in a septic patient is recognition
many of the available tests have problems with test performance that delay is associated with a poor outcome in sepsis. However,
(sensitivity, specificity, negative- and positive-predictive values) this therapy can then be tailored to the specific microorganism
and cost. These are discussed further below. identified and its antibiotic susceptibility. Various options for
treatment modifications at 48-72 h are available (for example,
discontinue antibiotics, continue the same antibiotics, review
the dose or route of administration, or de-escalate to a narrower
spectrum agent).

End of treatment of maximum benefit to patient care. There are also specific
technological advances that aim to improve the service further.
Many patients are currently treated with defined courses of
antibiotics (for example, 5 days, 7 days, 10-14 days), but there Microbiology laboratories have only recently been automated to
is little evidence to support the choice of treatment duration in any significant extent. While analysers have been widely used for
most situations and these durations are often arbitrary. Indicators specific indications for many years, for example, for serological
of the inflammatory or acute phase response, such as the analysis or incubating blood cultures, routine bacterial culture
C-reactive protein and procalcitonin, have been proposed as is still a very manual process requiring a relatively large
tests that could be used to provide assurance that a patient has number of staff compared to some other laboratory specialties.
recovered from an infection and that antimicrobial therapy can However, in the past decade, there have been major advances
be stopped. This is elaborated further below. in microbiology automation, which are now in widespread use.
While many of these developments have been designed to
THE ROLE OF THE LABORATORY enable higher laboratory throughput of specimens at lower cost,
IN STEWARDSHIP they can also have positive benefit for stewardship activities. As
well as improving laboratory turnaround times, automation can
The microbiology laboratory can have a significant role in provide greater consistency of culture between samples and,
facilitating many of the activities that optimise antimicrobial use. in some cases, improve the yield of organisms from cultured
Although the structure of the antimicrobial stewardship team samples.
itself may very in detail from one country to another, often a
medical microbiologist is a key member and their close day-to- Newer technologies, such as matrix assisted laser desorption
day working relationship with the laboratory means that many ionisation time of flight (MALDI TOF) mass spectroscopy, have
activities are intertwined. These include procedures for reporting been utilised in the last few years to identify bacteria to species
significant results, giving advice about best use of the laboratory, level much more rapidly and cheaply than was possible before.
recommending antimicrobial treatment regimens, developing It has become possible to identify isolates from blood cultures
guidelines and participation in audit. The laboratory also within hours of the cultures signalling positive, which means that
participates in surveillance, both at a local and higher level. This tailored antimicrobial therapy can be given.
aids the development of local resistance profiles to guide the Antimicrobial susceptibility testing is a key area of laboratory
choice of empirical therapy and also feeds into regional, national practice that has a major impact on antibiotic prescribing. The
and international surveillance. intention of susceptibility testing is to give the clinician an
Laboratories can optimise the information that they provide to indication as to whether-or-not an infection is likely to respond
clinical teams in a number of ways. Firstly, they can assure the to a specific antibiotic or not. This is often done by attributing
quality of the results they provide by complying with national and a label of ‘sensitive’ or ‘resistant’ to the report. As knowledge
international guidance on laboratory test methods. In the UK, of antimicrobial resistance and its detection has become more
these include the Standard Methods for Investigation. There are sophisticated, the information that is given has become much
laboratory accreditation requirements, such as those run by the more reliable. The cut off, or breakpoint, between sensitive
UK Accreditation Service (UKAS) designed to assess compliance and resistant can now be calculated scientifically when
with the ISO15189 standard. These may be mandatory or form compared to the somewhat arbitrary thresholds that were
part of the healthcare commissioning process. Laboratories also used historically. Much work has been done by the two major
participate in internal and external quality assurance schemes. scientific bodies in this area, the Committee for Laboratory
Science and Investigation (CLSI) and the European Committee
Considering the specific areas of interest for stewardship, on Antimicrobial Susceptibility Testing (EUCAST), to harmonise
laboratories can often optimise their service by liaising with breakpoints and make sure that laboratory susceptibility testing
their users to tailor what they do to meet the demands of the is more informed and consistent than previously.
clinical service. Timeliness of reporting is one simple example of
this. Ideally, reports should be available to clinicians at the time There are automated susceptibility testing methods in use in
that they want them to make clinical decisions. Often, relatively many laboratories, such as provided by VITEK™ or Phoenix™
straight forward enhancements to the laboratory service can machines, amongst others. These are able to give the species
make a large difference. An example would be extended identification of the bacterium as well as the minimum inhibitory
laboratory opening hours, 7 day per week working and reporting concentration (MIC) for a variety of different antimicrobials.
to meet deadlines of ward rounds or patient review. Again, these are useful for standardisation of reporting.
These issues could all be considered to be general best practice

to enhance the output of the laboratory and ensure that it is

They are, however, more expensive than some other testing

methods.
Restrictive reporting of the results of antimicrobial susceptibility
TOOLKIT RESOURCE
testing is one stewardship activity that varies from laboratory SITE LINK
to laboratory and, perhaps, may be underused. Within the UK,
UK Standard Methods for Investigation
it is common practice for the reporting of susceptibility results
to be limited to those antibiotics that the medical microbiologist European Committee on Antimicrobial Susceptibility
wants the clinician to prescribe. That is, results for agents that Testing (EUCAST)
fall outside the local prescribing formulary or are inappropriate
for the particular infection can be hidden from view. Such a These two websites are examples of guidance for
restrictive reporting practice has been shown to influence laboratories on how to perform existing diagnostics tests in a
clinician prescribing behaviour. Indeed, even the order in which standardised manner and to the optimal quality
the antibiotic susceptibility results are presented can change
prescribing, with those agents put at the top of the list more PDF ARTICLE
likely to be prescribed.
Consultation on Report from the European
An important growth area is the use of whole genome Committee on Antimicrobial Susceptibility Testing
sequencing. This has been made possible by the development (EUCAST) Subcommittee on the Role of Whole
of new technologies that can provide sequence data in a Genome Sequencing (WGS) in Antimicrobial
timescale that is clinically useful and at an ever decreasing cost. Susceptibility Testing of Bacteria. European Committee
Sequencing has been used to create a genetic ‘fingerprint’ of on Antimicrobial Susceptibility Testing. 2016
organisms for epidemiological purposes. The sequence may
also provide species identification information and, usefully, also
VIDEOS
indicate the presence or absence of genes encoding resistance
mechanisms. A recent EUCAST consultation has discussed the Podcasts from the British Society for Antimicrobial
uses and current limitations of this information. However, for Chemotherapy (BSAC) Antimicrobial Resistance Roundtable
some infections, most notably tuberculosis, sequencing is being series 5 Feb 2015 – lectures on diagnostic tests and
used routinely to guide treatment options and has the capability antimicrobial stewardship by:
to provide information much more quickly than traditional Peter Hawkey
mycobacterial culture techniques.
WATCH VIDEO
ROLE OF THE CLINICIAN
IN LABORATORY TESTING Alex Van Belkum
The value of a laboratory test is dependent on several

factors, including the performance characteristics of the test
WATCH VIDEO
(sensitivity, specificity, positive- and negative-predictive value).
Some factors are influenced by the clinician requesting the SITE LINK
test, such as how the sample has been taken and then
Examples of educational activities to improve the use
transported to the laboratory and what clinical information is
of urine dipsticks in the ‘To Dip or Not to Dip’ initiative
provided with the request. However, how the test is used in
clinical practice is also key. In the wrong setting, a test result This slide resource aims to educate healthcare professionals
may not only be unreliable, but often frankly misleading. on the correct use of urine dipsticks and thereby reduce
Clearly, in these circumstances there may be an adverse inappropriate antibiotic prescribing in elderly patients who do
impact on antimicrobial prescribing. It is crucial that clinicians not have genuine urine infections
understand these limitations of the tests they order and help
the laboratory perform the correct investigations and produce
a meaningful result.
Many pathogenic microorganisms may be found as part of the

normal commensal flora. Isolation of these organisms may not
necessarily indicate infection. Likewise, many body sites have

a normal commensal flora and samples sent to the laboratory in marker of various inflammatory conditions, it is not specific for
the absence of signs or symptoms of infection may be difficult to infection and is slow to respond to an infective stimulus.
interpret. Therefore, the clinician must understand the limitations
Many other indicators of the acute phase response have been
of testing and result interpretation and be able to put these into
described and these include various cytokines and plasma
clinical context rather than simply take a result at face value.
proteins, including albumin and ferritin. However, most of
A common mistake is to send a sample for a wide range of these have not been shown to be clinically useful in the acute
diagnostic tests when the likelihood that the patient has the management of infection.
conditions concerned is low. This is particularly the case in the
C reactive protein (CRP) is produced by the liver in response to
community, where often the pre-test probability that a patient
the release of pro-inflammatory cytokines. It rises and falls more
has the condition that is being tested is low. This often means
quickly than ESR and therefore can be used to indicate the onset
that a positive test result is more likely to be a false-positive
of an inflammatory process in the body and monitor its progress.
result than a genuine result. Again, the implication of this is that
It is not specific to infection, but can be useful to differentiate
a patient may be given an incorrect diagnosis and be treated for
between a bacterial and a viral infection and therefore has
something that they do not have. Equally important, they are not
potential to be used to guide initiation of antimicrobial therapy.
treated for whatever it is that they do have.
Procalcitonin (PCT), a precursor of calcitonin, is synthesised
A blood culture can easily be contaminated with skin organisms
by various tissues in response to inflammation and appears
at the time that the sample is being taken. Historically, up to 10%
to be more specific for bacterial infection. Hence there has
blood cultures were contaminated in this way, although with
been considerable interest in its potential use for antimicrobial
better aseptic sampling techniques, contamination rates can
stewardship. Specific areas that have been investigated include
be 3% or lower – much improved, but still significant. Patients
the use of PCT as a guide to the diagnosis of sepsis and the
with contaminated blood cultures are often commenced on
duration of antimicrobial therapy, predominantly in the critical
unnecessary antimicrobial therapy while the issue is being
care setting.
investigated. They may also have other investigations to
investigate an infection that they haven’t got. Many factors influence the value of biomarkers in antimicrobial
stewardship. Logistic issues, such as transport of samples to
An important example of a laboratory test being interpreted
wherever the test is being performed, play a big part, as they are
incorrectly is the overuse of urine dipsticks in the diagnosis of
critical to the turnaround time. Whatever test is performed, if it
urinary tract infection. These are widely seen as a simple test
not available at the time a prescribing decision is being made, it
that can be used at point-of-care to detect patients with urinary
cannot be clinically useful. This is why point-of-care testing is so
tract infections that require antibiotic treatment. However, their
appealing as a concept. However, point-of-care testing can often
value depends critically on the patient group in which they are
be more expensive than testing on a larger scale in a central
being used. In the elderly, asymptomatic bacteriuria is very
laboratory and, given that the same standardisation issues
common and a positive dipstick test does not necessarily mean
apply to point-of-care testing as to laboratory testing, there can
that the patient needs treatment. Overall, this may represent
be problems with training, quality assurance and hence test
one of the largest areas of antibiotic overtreatment and quality
performance. Nevertheless, NICE guidance for the management
improvement programmes to educate users about appropriate
of lower respiratory tract infection in the community
use and interpretation of dipsticks are part of many stewardship
recommends the use of CRP as a point-of-care test in the GP
activities. Conversely, in very young infants, not only are good
surgery. Fundamental to the success or failure of biomarkers in
urine samples more difficult to obtain, but dipsticks may lack the
stewardship are data to demonstrate that patient outcomes are
sensitivity to detect all urine infections.
improved in order to justify the increased cost.
ACUTE PHASE PROTEINS AND

OTHER BIOMARKERS
TOOLKIT RESOURCE
For many years it has been recognised that bacterial sepsis is
accompanied by an inflammatory response, the acute phase
SITE LINK
response, and that various biomarkers increase in concentration Podcast from the Federation of Infection Societies
in the blood as a result. At its most general level, an increase (FIS) annual conference ‘2013 – Action on Infection’ –
in fibrinogen levels in blood increases plasma viscosity and Matthew Dryden lecture on diagnostics in stewardship
this can be measured easily and cheaply as the erythrocyte and procalcitonin (PCT) ‘Does smarter testing improve
sedimentation rate (ESR). However, although the ESR is a useful patient outcomes?’

CHAPTER 8
AUTHORS: ALASDAIR MACGOWAN & MELISSA BAXTER
OPTIMISING STEWARDSHIP
THROUGH BETTER PK-PD
LEARNING OUTCOMES
CHAPTER IS TO: • Become familiar with terms pertaining to PK-PD
The aim of this chapter • Appreciate the complexities of PK-PD of antibiotics.
is to provide a basic • Appreciate the clinical circumstances that might demand altered antimicrobial
understanding of the dosing/regimens
principles of pharmacokinetics
• Understand the rationale behind bespoke dosing regimens.
and pharmacodynamics
underpinning antimicrobial • Appreciate the benefits to antimicrobial stewardship of understanding drug exposure
use. Such an understanding response relationships and optimizing PK-PD
will allow optimal use of
antinfectives for individual PHARMACOKINETICS AND PHARMACODYNAMICS (PK-PD)
patients and in so doing, aid in Definitions of pharmacokinetic and pharmacodynamic properties
antimicrobial stewardship by
optimizing clinical outcomes,
reducing antimicrobial PK Pharmacokinetics - How a drug moves through the body
resistance and adverse events. PD Pharmacodynamics- concentration effect relationship - the effect
may be related to the infecting agent (kill or resistance) or host
(adverse events)
MIC Minimum inhbitory concentration
MBC Minimum bactericidal concentration
Cmax Peak antibiotic concentration
AUC Area under the plasma concentration curve
Concentration Greater killing as the ratio of drug concentration to MIC increases
dependent killing in the therapeutic range
Time dependent Effect depends on duration unbound drug is at concentrations
killing exceeding the MIC
Volume of Virtual space into which a drug distributes assuming uniform
distribution concentrations
Bacteriostatic Inhibitis microbial growth and replication
Bacteriocidal Causes bacterial death
Post antibiotic Maintained suppression of bacterial growth following exposure to
effect (PAE) an antibiotic

CHAPTER 8 - OPTIMISING STEWARDSHIP THROUGH BETTER PK-PD
ASPECTS OF PK-PD
PHARMACODYNAMIC PARAMETERS dosing interval affects AUC: MIC and T>MIC. For concentration
PREDICTIVE OF OUTCOME dependent agents an increase in volume of distribution will
reduce the ability for a standard dose to achieve a high Cmax.
T > MIC Duration of time drug concentration is above Hydrophilic agents (beta-lactams, glycopeptides,
the MIC aminoglycosides) are unable to passively diffuse through the
Cmax:MIC Ratio of maximal drug concentration to MIC cytoplasmic membrane and are inactive against intracellular
AUC0-24:MIC Ratio of 24 hour area under the plasma organisms. They have a limited extracellular distribution and are
concentration time curve to MIC often excreted renally. Conversely lipophilic agents (macrolides,
tetracyclines, fluoroquinolones) freely cross membranes and
therefore have activity against intracellular organisms, wide
COMMONLY USED ANTIMICROBIAL distribution, and intracellular accumulation and often undergo
PHARMACODYNAMIC PARAMETERS hepatic metabolism.
In setting a susceptibility breakpoint, resistance mechanisms,
Antimicrobials differ in their pharmacokinetic and
site of infection and dosing regimen must be considered.
pharmacodynamic (PK-PD) behaviour. The PK-PD measure that
Furthermore, serum concentrations may not absolutely predict
correlates with efficacy depends on the bactericidal activity and
clinical outcome - the concentrations at the site of infection may
duration of persistent effects of the agent. For time dependent
be more important.
agents, the rate of bacterial killing is maximised at a low multiple
of the MIC and achieving higher concentrations does not result
in greater killing. For concentration dependent agents there
is greater killing as the ratio of Cmax: MIC increases within
pharmacologically relevant concentrations. Altering the dose
primarily affects Cmax: MIC and AUC: MIC, whereas altering the

DISTRIBUTION METABOLISM
• lipid solubility • linear pharmcokinetics
• blood flow • once enzymes saturated
• protein binding small dose increase causes
• regional blood flow disproportionate increased
serum levels
PK
ABSORPTION EXCRETION
• Bioavailability • renal clearance
• Drug/food interactions • non-renal clearance
• GI conditions • biliary
• first /second pass metabolism • intestinal
WHEN IS PK/PD CLINICALLY RELEVANT?

Potential altered PK/PD Example
PATIENT FACTORS
Obesity Reduced tissue penetration Quinolones
• volume of distribution
Shorter mean T1/2 * Vancomycin • renal function
Increased Vd** Aminoglycosides • reduced protein binding
• Site of infection
Increased clearance Aminoglycosides
Renal insufficiency Decreased clearance Aminoglycosides
Neonates Decreased clearance Aminoglycosides
ANTIBIOTIC FACTORS
Glycopeptides
• hydrophillic
Children Increased clearance Aminoglycosides • Lipophillic
Critical illness Increased Vd Aminoglycosides • static
• cidal
Beta lactams
Glycopeptides
Colistin
Increased clearance Beta lactams
Pregnancy Increased clearance Aminoglycosides OPTIMAL PK/PD
Cefuroxime • Bespoke dosing
Increased Vd Hydrophilic agents
Cystic fibrosis Increased clearance Aminoglycosides
*T1/2 half life, **Vd volume of distribution)

PRIMARY
CLASS EXAMPLE EFFECT DISTRIBUTION EXCRETION PD PAE TDM
PARAMETER
Low protein
Short or no
Beta Lactams Amoxicillin Bactericidal binding and Renal T>MIC Not routine
PAE
hydrophilic
Recommended
Glycopeptides Vancomycin Bactericidal Hydrophilic Renal AUC:MIC Short PAE
for all patients
CMAX:MIC
Recommended
Aminoglycosides Gentamicin Bactericidal Hydrophilic Renal & Significant
for all patients
AUC:MIC
CMAX:MIC
Lipophilic wide Renal & Not
Fluoroquinolones Ciprofloxacin Bactericidal & Significant
distribution hepatobiliary recommended
AUC:MIC
T>MIC
Bacteriosta Lipophilic wide Not
Macrolides Azithromycin Hepatobiliary & Significant
tic distribution recommended
AUC:MIC
Bacteriosta Lipophilic wide Not
Tetracyclines Doxycyline Hepatobiliary AUC:MIC Significant
tic distribution recommended
Bacteriosta Lipophilic wide Demonstrated Not
Lincosamide Clindamycin Hepatobiliary AUC:MIC
tic distribution in S.aureus recommended
CF, ESRF,
neonates,
Bacteriosta Lipophilic wide burns, MIC
Oxazolidinone Linezolid Renal AUC:MIC Short
tic distribution >2mg/l
interacting
meds
Highly protein CMAX:MIC dosing >6mg/
Lipopeptide Daptomycin Bactericidal bound Renal & Significant kg, renal
hydrophilic AUC:MIC impairment
Colistin Hydrophilic
Recommended
Polymyxin (colistimethate Bactericidal and lipophilic Renal AUC:MIC Significant
for all patients
sodium) properties
CLINICAL APPLICATION OF PK/PD increased Vd, the free drug is diluted over the total body water.
IN SPECIAL CIRCUMSTANCES In severe hypoalbuminaemic states increased loading and
maintenance doses may be necessary when using highly bound
Critical illness
hydrophilic antibiotics.
Multi-organ failure can result in alterations to the absorption,
Augmented renal clearance risks subtherapeutic concentrations
distribution, metabolism and excretion of a drug. Under dosing
with time dependent antimicrobials. Where patients have acute
is associated with insufficient treatment and increased risk of
kidney injury the impact of altered PK depends on the proportion
resistance, and overdosing with toxicity.
of antimicrobial that is renally excreted. In general it is better to
Alterations in protein binding, fluid shifts into the interstitium prolong the dosing interval for concentration dependent agents,
and pH affect drug distribution. These are most relevant while maintaining an unmodified dose to maximize Cmax: MIC:
for hydrophilic drugs that have a relatively low Vd. Similar for time dependent agents dose reduction while maintaining the
concentration-time profiles are observed with lipophilic agents in dosing interval maximizes T>MIC.
critically ill and non-critically ill patients.
With respect to protein binding, only the unbound portion Ventilator associated pneumonia (VAP)
is active. Higher proportions of unbound drug due to low With VAP there can be a large microbial load resulting in a
serum protein concentrations result in temporarily high drug population of resistant organisms present on initiation of
concentrations but as hypoalbuminaemia is associated with treatment. Killing the susceptible population can allow for

amplification of the non-susceptible sub population and Pregnancy

emergence of resistance during treatment. Considering drug Several physiological changes in pregnancy can impact on PK
exposure at the site of infection, it is suggested that optimal including:
pharmacodynamic exposures in the epithelial lining fluid (ELF)
• Increased maternal fat and total body water
are a better predictor of appropriate pneumonia treatment for
extracellular pathogens than plasma. This is however unvalidated • Reduced plasma protein levels
by clinical studies. • Delayed gastric emptying
• Increased gastric pH
Cerebrospinal fluid (CSF)
• Increased cardiac output and renal blood flow
Penetration to the CSF and extracellular space of the brain
• Altered activity of hepatic metabolizing enzymes.
is dependent on molecular size, lipophilicity, plasma protein
binding (only the unbound fraction can freely penetrate). Serum levels of many drugs are lower in pregnancy largely
Concentration of antibiotics in the CSF is also dependent due to the increased renal clearance and expanded
on their affinity for transport systems responsible for the intravascular volume.
removal of toxic compounds from the CNS. Infection of the
Dose
CNS causes an increase in permeability of the blood-CSF/ Standard FDA
Antibiotic alteration in Notes
Blood-brain barrier and decrease in CSF flow leading to an dose category*
Pregnancy
increase in drug concentrations during inflammation. The most
2g Once
important determinant of efficacy in meningitis is the relationship
daily IV Not
between antibiotic concentration in the CSF and the MBC of Ceftriaxone B
(non CNS required
the organism. Intraventricular administration of antibiotics in
infection)
addition to systemic therapy is used for antimicrobials with poor
penetration into the CSF and/or high systemic toxicity such as Lower
aminoglycosides, vancomycin and polymyxins. Increase serum
750mg
Cefuroxime dose B levels and
TDS IV
suggested shorter
T1/2
Interstitial 4500mg Not Avoid 1st
fluid shifts Metronidazole B
TDS PO required Trimester
Shorter
dosing
500mg Lower
Increased renal interval or
Delayed gastric Penicillin V -1g QDS B serum
clearance or acute increase
emptying PO levels
kidney injury dose
suggested
5mg/kg 5mg/kg
Gentamicin C
IBW ABW
No dose High
250-
Physiological alteration variability
changes in critical Erythromycin 500mg B
recommen- in serum
illness contributing QDS
ded levels
to altered PK
Dose
based Monitor
Vancomycin B
on renal TDM
function
Changes in Changes in serum TABLE 2

regional blood flow protein levels Suggested dosing of commonly used antimicrobials in pregnancy based
of PKPD
* FDA categories: A – well controlled studies failed to demonstrate risk in first
Physiological changes in critical illness affecting PK trimester. B –animal reproduction studies failed to demonstrate risk C – animal
reproduction studies have shown an adverse effect on the foetus

Neonates As well as increased percentage of fat per kg of bodyweight,

Newborns have drug clearances that differ from children obese individuals have a larger absolute lean body mass
and adults and immature renal function in neonates requires (LBM), with lean components accounting for 20-40% of excess
antibiotic dosing adjustment. Aminoglycosides are commonly body weight.
given neonates, their pharmacokinetic parameters differ among Loading doses are based on Vd, and should be based on ideal
neonates and the gestational age is an important factor in body weight (IBW) when the distribution of a drug is restricted
determining variability. Gentamicin has a long T1/2 and large to lean tissues. For drugs distributed mostly in lean mass
Vd especially in premature infants that increases with sepsis, and partly fat tissue a calculation of loading dose should be
when the Vd is large a dose of 5 mg/kg is optimal. Clinically, performed with IBW plus a percentage of EBW and loading
renal function is the most important factor for elimination. dose for drugs equally distributed in fat tissues should be TBW.
Gentamicin trough concentration >2 mg/l is associated with Hydrophilic antibiotics distribute well in water but not adipose
toxicity, and peak <5 mg/l associated with reduced efficacy. tissue. As the water content of adipose tissue approximates 30%,
Late onset sepsis caused by coagulase negative staphylococci or the Vd for hydrophilic drugs may be only 0.3 of the Vd
methicillin resistant Staphylococcus aureus (MRSA) has resulted in other tissues. This distribution into the water component
in an increased administration of vancomycin in neonates. As of adipose tissue may warrant increasing the dose in proportion
with gentamicin, vancomycin pharmacokinetics are different in to the excess body weight using the dosing weight correction
neonates due to higher extracellular fluid volume and limited factor (DWCF)
renal elimination capacity and the vancomycin PK is significantly
altered as neonates mature. Risk factors for developing Weight
Calculation M Calculation F Notes
nephrotoxicity related to vancomycin treatment are trough measure
concentrations greater than 10 mg/l, concomitant treatment Dose used
with an aminoglycoside and treatment beyond 21 days, others for lipophilic
Total (actual)
include high peak concentrations, high total dose, pre-existing agents
body weight Patient weight in kgs
when renal
renal failure, and concurrent treatment with amphotericin or (TBW)
clearance is
furosemide. normal
IBW (devine
Several
formula - 50 + (2.3 45 + (2.3 x
variations on
surrogate x height in height in
TOOLKIT RESOURCE marker of inches over inches over
this equation
have
lean body 60") 60")
ARTICLES mass)
emerged
Neonatal TDM and dosing Excess body

EBW = TBW - IBW See DWCF
weight
National Institute for Health and Care Excellence Corrects for
(NICE) (2012) Neonatal infection (early onset): additional
antibiotics for prevention and treatment. Dosing water content
NICE clinical guideline CG149 weight of adipose
correction tissue - for
Dosing weight - DWCF (TBW-
factor use with
Ku LC, Smith PB. Dosing in neonates: special IBW) + IBW
(DWCF)/ hydrophilic
considerations in physiology and trial design. adjusted bodt agents, DWCF
Pediatric research. 2014. Doi:10.1038/pr.2014.143 weight (ABW) value varies
depending on
the agent
TABLE 3
Obesity
Definitins of weight measures and suggested use
Pathophysiological alterations in obesity can cause changes
in PK-PD necessitating weight related dosage adjustments
for antimicrobials. Fixed regimens can lead to under dosing
or total body weight based dosing to overdosing and toxicity.
Blood flow in fat is poor and accounts for 5% of cardiac output
compared to 22% in the lean tissue.

Increased body
mass (lean and fat)
Increased cardiac
changes in regional
output and blood
blood flow
volume
Physiological
changes in obesity
contributing to
altered PK
Changes in serum Increased renal

protein levels clearance
hepatic metabolic
changes
Physiological changes in obesity contributing to altered PK
Drug Obesity dosing Comments
Higher doses may be necessary in obesity to achieve

Beta lactams Consider larger doses
adequate [ ]
Reduced T1/2 allows more frequent maintenance dosing

Vancomycin TBW to avoid large peak [ ] with larger doses and overcome
increased clearance
Diminished serum levels in obese

Linezolid Unchanged
patients but clinical cure achieved with standard dosing.
BNF: IBW
Gentamicin Early TDM essential
40% addition of EBW (TBW-IBW) to IBW
Data suggests outcomes similar with IBW dosing but

Daptomycin TBW
may be MIC and organism specific. TDM recommended
Higher plasma peak [ ] required to give

ABW to achieve adequate tissue
Ciprofloxacin the same tissue penetration in obese
penetration
vs. non obese.
TABLE 4
Suggested dose alterations in obesity

The impact of haemodialysis on drug therapy depends on

molecular weight, degree of protein binding and Vd of the drug.
TOOLKIT RESOURCE CRRT is a generic term encompassing various modalities of
continuous haemodialysis or haemofiltration commonly used to
SITE LINKS
support critically ill patients with acute or chronic renal failure.
UKMI dosing in obesity Rate of drug clearance during CRRT can be highly variable in
critically ill patients.
Dosing in Obesity
Wurtz R, Itokazu G, Rodvold K. Antimicrobial dosing Following dialysis, supplemental dosing should be considered.
in obese patients. Clin Infect Dis. 1997;25(1):112–8 Serum trough levels of antibiotics such as gentamicin and
vancomycin should be measured immediately after dialysis to
determine the need for ongoing doses.
Medicines Q &As. How should antibiotics be
dosed in Obesity?
Drug dosing in extremes of body weight in

critically ill patients. 1st edn (V1.0). 2013
TOOLKIT RESOURCE
PDF ARTICLE
Dosing in Renal failure
Matzke GR, Aronoff GR, Atkinson Jr AJ, Bennett
Burns
WM, Decker BS, Eckardt K-U, et al. Drug dosing
Pharmacokinetics of antibiotics can be significantly altered in consideration in patients with acute and chronic
burns patients. The factors affecting PK include the area and kidney disease—a clinical update from Kidney
depth of the burn, presence of sepsis, degree of hydration, Disease: Improving Global Outcomes (KDIGO).
serum protein concentrations, age, creatinine clearance and Kidney Int. 2011;80:1122–37
time after injury. In the acute phase of burn injury (lasting
approximately 48 hours) altered capillary permeability results
in loss of protein rich fluid from the vascular system. Resultant
Where can PK/PD be suboptimal? Worked example with
hypovolaemia can lead to reduced cardiac output, tissue
Colistin dosing
hypoperfusion and reduced renal blood flow and function.
Beyond 48 hours of injury, the second, hypermetabolic phase The standard dose of colistin (9 Megaunits loading followed by
is characterized by an increase in cardiac output with and 3 megaunits three times per day maintenance) is administered.
increased blood flow to kidneys and liver. Creatinine clearance For each scenario the effect on the time-concentration curve is
may become significantly elevated. demonstrated.
The emergence of multi drug resistant Gram-negative bacteria
Renal failure has led to a revival of the polymyxins. Polymyxin E – colistin is
Renal function is especially important for hydrophilic used frequently as salvage therapy for nosocomial infections
antimicrobials that are almost entirely renally excreted, lower caused by Pseudomonas aeruginosa, Acinetobacter sp and
doses are needed with impaired renal function. carbapenemase producing Enterobacteraciae. Use of colistin
In patients with moderate to severe chronic kidney disease (CKD) had largely been abandoned due to frequent toxicity, namely
the Vd is increased due to reduced protein binding, increased dose dependent nephrotoxicity and neurotoxicity. Colistin exists
tissue binding or fluid overload. in two forms; colistin sulfate used for bowel decontamination
Where renal replacement therapy is necessary a variety of and topical treatment and the intravenous form of the prodrug
methods from peritoneal dialysis, intermittent hemodialysis colistimethate sodium.
and continuous renal replacement therapy (CRRT) all vary in
efficiency of solute removal.
Access to the peritoneal cavity for dialysis allows for local
and systemic drug delivery. As the rate of clearance is low
(~10ml/min) peritoneal dialysis does not enhance drug removal
to the degree that requires dose modification, therefore
recommendations are as for those with eGFR or creatinine
clearance <15 ml/min.

INTERACTIVE CASE STUDY

A 58-year-old female is transferred to your hospital following 4. Review the patients clinical progress.
a road traffic accident whist holidaying in Turkey. Amongst her 5. All of the above
injuries she sustained a fractured femur that required insertion
of a femoral nail. You are contacted by the clinical team as the
patient has been spiking temperatures above 38oC for several
days with raised inflammatory markers CRP 130mg/L and WCC
SEE ANSWER
15.6 x109. She has deteriorated today and is now rigoring,
tachycardic and requiring fluid boluses to maintain her blood
pressure. The wound appears erythematous and is leaking
serous fluid. Empiric meropenem 1g tds is commenced. The The following day the blood culture report reads as follows:
following day blood cultures are positive with Gram-negative
Isolated after 27 hours incubation in Aerobic and anaerobic
rods on microscopy. Swabs of the surgical site have provisionally
bottles
isolated Klebsiella pneumoniae.
Klebsiella pneumoniae:
What are your immediate actions? Amikacin R
1. Inform the surgeons that washout is necessary to Aztreonam R
control sepsis.
Ceftriaxone R
2. Check CPE screen results.
Ceftazidime R
3. Infection control precautions as CPE positive until
Ciprofloxacin R
proven otherwise.

Co-amoxiclav R Referred to reference laboratory for confirmation of mechanism.

Cotrimoxazole R
Which treatment options should be considered?
Ertapenem R
1. Meropenem monotherapy
Gentamicin R
2. Meropenem plus colistin
Meropenenm R
3. Meropenem plus aztreonam
Piperacillin/tazobactam R
4. Colistin monotherapy
ESBL: Detected 5. Meropenem plus fosfomycin plus colistin
Meropenem, ertapenem, aztreonam, tigecycline, colistin,

fosfomycin MIC to follow
Disc testing for carbapenemase production to follow
SEE ANSWER
Which of the following PK-PD factors will influence your
recommended treatment?
The optimal treatment regimen for CPE infection is yet to
1. Meropenem and Ertapenem MIC be defined. In general combination therapy is preferred
2. Renal function and outcomes are improved when a carbapenem is added
3. Site of infection to the regimen. Colistin monotherapy has been associated
4. Allergies with treatment failure. Aztreonam retains activity against
some carbapenemase enzymes (metallobetalactamases)
5. Weight
but it is inactivated by the ESBL, depending on the type of
carbapenemase produced meropenem and aztreonam may
be a useful combination in that the ESBL can be inhibited by
meropenem and the carbapenemase by aztreonam. Fosfomycin
SEE ANSWER has shown activity against KPC producing enterobacteraciae
but its use has been associated with relapse and emergence of
resistance amongst susceptible isolates in vivo.
Despite CPEs being able to hydrolyse carbapenems outcomes
are improved when a carbapenem is added to the regimen. CONTINUOUS INFUSIONS OF
Renal function must be taken into account as large doses of BETA-LACTAM ANTIBIOTICS
carbapenems are indicated given the higher MICs of CPEs as
In attempt to mediate the risk of subtheraptetic serum levels
well as nephrotoxic agents such as colistin and aminoglycosides
and potential treatment failure with antimicrobials time
being used in combination. Site of infection is of importance as it
dependent antimicrobials there is debate over whether these
is necessary to understand how likely it is to achieve therapeutic
should be administered as standard doses, as an intermittent
antimicrobial levels in certain compartments, and here the aim is
bolus or as continuous infusion and is focused on beta lactams.
to penetrate bone. Patient weight is also an important factor in
It is suggested that therapeutic targets for continuous infusion
determining the ability to attain high antimicrobial levels in the
therapy should be a steady state concentration Css that is 4x
target area. Allergy is important for all antimicrobial prescriptions
the MIC.
but is not a PK or PD parameter.
Where bacteria have low MICs and are in the susceptible
Further sensitivities are available: range there may be little benefit to continuous infusion over
Meropenem MIC 8 mg/l R intermittent bolus, however the latter may fail with pathogens
Ertapenem MIC 32mg/l R with a higher MIC. Where there is renal impairment the
utility of continuous infusion is less relevant as beta lactam
Aztreonam MIC 16mg/l R
clearance will be impaired. Several meta-analyses and double
Tigecycline MIC 0.12mg/l S blinded randomized controlled trials have reported results
Fosfomycin MIC 1024 mg/l R trending towards improved clinical outcomes but the lack of
Colisitin MIC 0.25 mg/l S standardisation amongst studies with regards to dosing, PK/PD
parameters, patient population has made the therapeutic PD
Disc testing: Carbapenemase detected. benefit less clear.

THERAPEUTIC DRUG MONITORING (TDM) strains combination therapy is the cornerstone of therapy on
the basis that singularly resistant and inactive antibiotics can
TDM is used to optimise antibiotic use with the overall aims
obtain a synergistic or additive effect. Therapy for multi-drug
of improving exposure and outcomes, minimizing toxicity and
resistant and pan-resistant strains of P.aeruginosa depends on
ultimately reduce antimicrobial resistance. It is most commonly
the mechanism of resistance but largely encompasses colistin in
employed for drugs with a narrow therapeutic range and is
combination with an antipseudomonal carbapenem
likely to be beneficial in populations where there is profound
PK variability such as critical illness. TDM is used to ensure that
target exposures are being achieved, as previously discussed RESISTANCE SUPPRESSION
certain patient populations may be expected to have altered PK Subpopulations with reduced antibiotic susceptibility are a
such that the recommended dose from the drug manufacturer normal feature of dense populations especially P. aeruginosa
may not be sufficient to achieve therapeutic targets. The MIC of and Staphylococcus aureus. The likelihood of antibiotic
the organism can also impact on the dose necessary to achieve treatment provoking the emergence of resistant subpopulations
target concentrations. For certain antimicrobials the outcomes of depends on the propensity for resistance within the population
certain infections correlate with the AUC: MIC ratio which in turn (spontaneous mutation rate), host defenses controlling the
correlates with serum trough levels, such that the trough level growth of the resistant subpopulation and antibiotic drug levels
is a surrogate PK measure. For example when treating MRSA at the site of infection. It is suggested that drug levels should
infections with vancomycin a trough concentration of 15 mg/l will at least exceed 8-10 times the MIC to prevent emergence of
result in an AUC: MIC ratio of >400 and is therefore a suitable resistant subpopulations. As drug exposures increase, the
target for therapy. selective pressure increases causing more injury to the fully
susceptible population of bacteria relative to the less-susceptible
COMBINATION THERAPY population causing their amplification. Once a sufficient
exposure is then achieved resistance suppression is achieved.
Optimising combination treatment is vital for difficult to treat
However there has been little focus on the impact of dosing and
organisms such as Pseudomonas aeruginosa, Acinetobacter sp
probability of resistance emergence. Strains with MICs close to
and multi-drug resistant Enterobacteraeciae owing to single or
the clinical breakpoint are at risk of emergence of resistance
multiple resistance mechanisms.
when treated with monotherapy.
There are several reasons to combine antimicrobial therapy;
to broaden spectrum, achieve improved activity/synergy and TOXICODYNAMICS
to suppress the emergence of resistance. With regard to
MDR Enterobacteraciae such as KPC (Klebsiella pneumoniae Toxic side effects can occur as plasma and tissue drug
carbapenemase) reduced risk of death with bacteraemia has concentrations increase that may be a result of accumulation
been observed when antimicrobial regimens include more if kidney and liver function has deteriorated. Toxodynamic
than one drug with in vitro activity against the organism and modeling can be used to estimate the concentrations associated
enhanced efficacy is observed when a carbapenem is used. with probable toxicity.
Treatment of severe infections by P. aeruginosa is challenging.

Dose dependent
Limited by the few anti-pseudomonal antibiotics available Antibiotic Manifestation
toxicity
and its ability to acquire resistance by several mechanisms
(degrading enzymes, reduced permeability, active efflux and Increased serum urea
target modification). Multidrug resistance, defined as resistance and creatinine
to carbapenems, aminoglycosides and fluoroquinolones Colistin Nephrotoxicity Dizziness, weakness,
is frequent and isolates resistant to all antipseudomonal paraesthesia, vertigo,
(colistimethate
antibiotics increasingly common. Combination therapy has visual disturbance,
sodium) Neurotoxicity
been more controversial in treating P. aeruginosa, failing to confusion, ataxia,
improve survival in bacteremia or affect outcome in VAP. neuromuscular
The nature of the resistance mechanism may undermine the blockade
use of combination therapy in P.aeruginosa infections, such Penicilin Neurotoxicity Twitching, seizures
as single efflux mutations affecting both beta lactams and Imipenem/cilastatin Neurotoxicity Seizures
fluoroquinolones. When resistance is mutational meropenem
and tobramycin are most likely to retain activity for the beta
lactam and aminoglycoside classes. For multi-drug resistant

Anaemia, leucopenia, OPTIMISING PK/PD FOR ANTIMICROBIAL

pancytopenia, STEWARDSHIP
Bone marrow thrombocytopenia Many pathogens have demonstrated high-grade resistance to a
suppression Nausea, vomiting, range of antibiotics such that multidrug resistance is recognized
Lactic acidosis abdominal pain, as a global problem and major public heath concern.
Linezolid
hyperventilation, low
In light of this, coupled with the declining rate of antimicrobial
Peripheral/Optic biocarbonate.
drug discovery, the utility of PK-PD relationships to optimise drug
neuropathy Change to acuity, exposure is increasingly recognised to ensure clinical outcomes
colour vision, field while suppressing the emergence of antimicrobial resistance.
defect, blurred vision Suboptimal antimicrobial concentrations trigger development
Leukopenia, of multidrug resistance. Improving outcomes from infection
Bone marrow neutropenia, requires understanding of the interactions between the drug,
Co-trimoxazole
suppression thrombocytopenia, host and infecting pathogen. Antimicrobial stewardship employs
agranulocytosis the clinical application of PK-PD principles while providing the
Reversible narrowest coverage for the infection by optimizing the agent,
bone marrow Leukopenia, dose and duration with the aim of the best control of infection
suppression reticulocytopenia, whilst maintaining minimal impact on resistance selection.
Chloramphenicol
(Aplastic thrombocytopenia,
anaemia is dose anaemia
independent)
Increased serum urea
TOOLKIT RESOURCE
Nephrotoxicity and creatinine ARTICLES
Aminoglycosides Ototoxicity Hearing impairment, PK-PD. Levison ME. Pharmacodynamics of antimicrobial
vestibular disturbance drugs. Infect Dis Clin North Am. 2004;18(3):451–65.
MacGowan AP. Role of Pharmacokinetics and
Pharmacodynamics: Does the Dose Matter? Clin Infect Dis
Fluoroquinolones Neurotoxicity Seizures
2001 33(s3):S238–9.
Raised CPK, Myalgia,
Daptomycin Muscular toxicity
muscle weakness Emergence of Resistanc. Drusano GL, Louie A,Macgowan
A, Hope W. Suppression of Emergence of Resistance
PK- PD of new agents in Pathogenic Bacteria: Keeping Our Powder Dry, Part 1
There are many issues surrounding the introduction of new Antimicrob Agents Chemother 2016:60(3):1183-1193
antimicrobials into clinical use. They are often being used in
Drusano GL, Hope W, MacGowan A, Louie A. Suppression
salvage therapy and multi-drug resistant infections, for which
of Emergence of Resistance in Pathogenic Bacteria:
they may be being used out with their license. If being used in
Keeping Our Powder Dry, Part 2. Antimicrob Agents
areas such as critical care where altered PK is to be expected,
2015;60(3):1194–201.
then there may be little or no evidence to guide optimal dosing -
which is where there is a reliance on PKPD in vitro data to guide
SITE LINKS
dosing. Matters are complicated further by patients on renal
replacement therapy where variable amounts of drug may be Carbapenemase producing organisms
removed depending on drug factors and the method of renal Acute trust toolkit for the early detection,
replacement. In this situation TDM will guide dosing but this is management and control of carbapenemase-
hampered by the need to develop an accurate, validated assay producing Enterobacteriaceae Public Health
method having obtained from PKPD data expected targets England. 2013.
and toxicities. PHE, UK Standards for Microbiology Investigations.
Detection of bacteria with carbapenem hydrolysing
β-lactamases (carbapenemases).

CHAPTER 8 - ANSWERS
INTERACTIVE CASE STUDY ANSWERS Which of the following PK-PD factors will influence your
recommended treatment?
What are your immediate actions?
1. Inform the surgeons that washout is necessary to 1. Meropenem and Ertapenem MIC
control sepsis. 2. Renal function
2. Check CPE screen results. 3. Site of infection
3. Infection control precautions as CPE positive until 4. Allergies
proven otherwise.
5. Weight
4. Review the patients clinical progress.
5. All of the above
Answer 1,2,3,5
Answer 5.
At this point the concern is that the patient might
be infected with a carbapenemase producing
Klebsiella pneumoniae. With infection of orthopaedic Which treatment options should be considered?
devices antibiotic treatment alone is unlikely to 1. Meropenem monotherapy
suffice for anything other than superficial wound
2. Meropenem plus colistin
infection. Antibiotics should be given alongside
3. Meropenem plus aztreonam
surgical intervention that may include washout and
debridement or implant removal. As the patient has 4. Colistin monotherapy
been an inpatient in a hospital abroad they should 5. Meropenem plus fosfomycin plus colistin
be considered at risk of colonisation with a CPE as
per public health England guidance. This patient
should have been admitted to a side room and local Answer 2,3,5
infection control guidance followed regarding contact
precautions and screening for CPE. It is important
not to assume meropenem would suffice, as there is
concern of carbapenemase production.
BACK TO QUESTIONS

CHAPTER 9
AUTHORS: MARK GILCHRIST & ORLA GEOGHEGAN
THE STEWARDSHIP TOOLKIT

LEARNING OUTCOMES
CHAPTER IS TO: • Be aware of the tools available to carry out a baseline analysis of antimicrobial
Gain an understanding of stewardship within your organisation.
the different antimicrobial • Recognise key personnel who should be included in antimicrobial stewardship groups.
stewardship interventions
• Understand where antimicrobial stewardship groups fit within organisational structures.
that can be deployed as
part of an effective • Know how to identify areas where antimicrobial stewardship programs should
stewardship programme. be focused.
• Define core and additional interventions which can be employed in antimicrobial
Identify specific stewardship programs.
stewardship interventions • Be able to identify measures to assess the effectiveness of antimicrobial
that can be applied in your stewardship programs.
healthcare setting. • Recognise different routes of communication which may be used within an antimicrobial
stewardship program
Understand the ways in which
stewardship interventions
can be communicated to HOW TO IMPLEMENT A SUCCESSFUL ANTIMICROBIAL
engage clinicians. STEWARDSHIP PROGRAMME
It is recommended that you use a baseline checklist to assess current Antimicrobial
Stewardship (AMS) within the hospital. This can provide a useful gap analysis prior to
implementing an Antimicrobial Stewardship Programme (ASP). Baseline checklists are
available from CDC or NICE. You may find the Measurement for Improvement Toolkit from
the Australian Commission on Safety and Quality in Health Care resources useful in the
design of an ASP; you can access the toolkit here.
A proposed approach to implementing a successful ASP within an organisation is outlined

in figure 1.

CHAPTER 9 - THE STEWARDSHIP TOOLKIT
1
COLLECT BASELINE DATA WITHIN THE ORGANISATION
Antimicrobial use and expenditure trends over time
Local antimicrobial susceptibility data
SURVEY THE AMS CULTURE WITHIN THE ORGANISATION
2
Conduct a survey to determine the drivers for AMS within the organisation,
e.g. AMR, HCAI, financial
Assess the level of support for the ASP available from the executive team
Identify committees with an interest in AMS, e.g Drug and Therapeutics Committee;
define their responsibilities and develop a reporting structure
3
ASSESS THE RESOURCES AVAILABLE
Are there trained staff or staff willing to be trained in AMS?
- microbiology, ID, pharmacy, nursing
Do you have sufficent information technology resources to allow for easy surveillance?
4
REVIEW EXISTING ANTIMICROBIAL GUIDELINES AND POLICIES
Are they current, comprehensive, evidence based and tailored to local antibiograms?
Are they readily available at the point of prescribing?
Is there a named person responsible for content of guidelines
and policies and their implementation?
5
REVIEW COMMUNICATION WITHIN THE ORGANISATION
What are the methods used to communicate with patients, medical,
nursing and other staff?
How can these be utilised to provide communication around the ASP?
FIGURE 1
Proposed approach for implementing a successful ASP within an organisation

CLEAR AIMS AND

OBJECTIVES
OUTCOME NEED TO BE
MEASURES DEFINED ALONG
SHOULD BE WITH METRICS CLEAR LINES OF
REPORTED TO FOR MEASURING ACCOUNTABILITY
THE HOSPITAL OUTCOMES WITHIN THE
EXECUTIVE ORGANISATION
LINK TO OTHER
RELEVANT RESOURCES
TOP TIPS FOR A
COMMITTEES DEDICATED TO
SUCCESSFUL ASP
WITHIN THE AMS
ORGANISATION
ASP IS INCLUDED A
IN THE MULTIDISCIPLINARY
ORGANISATION’S ASP SHOULD ANTIMICROBIAL
QUALITY AND REVIEWED COMMITTEE SHOULD
SAFETY STRATEGIC REGULARLY BE CREATED
PLAN WITH TERMS OF
REFERENCE DEFINED
FIGURE 2
Top tips for a successful ASP
PROPOSED MEMBERS OF ANTIMICROBIAL PROPOSED MEMBERS OF ANTIMICROBIAL

STEWARDSHIP GROUPS STEWARDSHIP GROUPS
A successful antimicrobial stewardship group needs to • A senior leader who has experience of
include the core members of the AMS team in addition to implementing change
representatives from clinical specialities within the organisation. • Infectious diseases physician
Proposed members of antimicrobial stewardship groups are • Microbiologist
detailed in figure 3. • Antimicrobial pharmacist
• Representatives from clinical specialities
• Infection control representative
• Drug and Therapeutics committee representative
• Nurse representative
• Primary care representative
FIGURE 3
Proposed members of antimicrobial stewardship groups

POSITION OF ANTIMICROBIAL
STEWARDSHIP GROUPS WITHIN
THE ORGANISATION
One of the key elements of implementing a successful ASP
is establishing where the antimicrobial stewardship group
sits within the organisation. There must be clear lines of
accountability to the executive team and governing bodies
as well as other relevant committees within the organisation.
Figure 4 shows an example of where the antimicrobial
stewardship group lies within the organisational structure
in Imperial College Healthcare NHS Trust, a large multi-site
teaching hospital in London, England.
FIGURE 4
An example of where the antimicrobial stewardship group lies within the organisational structure in Imperial College Healthcare NHS Trust

HOW TO IDENTIFY PRIORITY AREAS IN

WHICH TO FOCUS ASP
ASP would cover the whole of the organisation, however many
centres are limited by the AMS resources available. In such
Complex
settings, priority areas for ASP should be identified and targeted.
patients,
Figure 5 provides suggested priority areas for targeting ASP.
i.e. ICU
Successful ASPs are continually reviewed and adjusted
according to changes in priority over time. Point prevalence
surveys, surveillance of AMR, surveillance of antimicrobial use Areas with high
and benchmarking with peers are useful tools to review priorities antimicrobial use
within an established ASP.
Areas with
Areas with high poor compliance
AMR rates to guidelines
Click on the icons in figure 6 to hear how teams have FIGURE 5

implemented ASPs across the world Suggested priority areas for targeting ASP
5
1 3
FIGURE 6 Videos:
Examples of implementation of stewardship from around the world 1 & 2 Dr Adrian Brink (S Africa)
3 Angeliki Messina (S Africa)
4 Dr James Hatcher (England)
5 Dr Sylvia Hinrichsen (Brazil)

THE ASP TOOLKIT

A successful ASP should include clinical leadership and
corporate responsibility. There is no “one size fits all” approach
to ASPs and programmes will vary according to the size and
specialities provided within your organisation. A global survey
of ASP found that there were many different AMS interventions
in use in different organisations (see figure 7).
FIGURE 7
Results of a global survey on types of AMS interventions employed as part of an ASP
For an AMS programme to be effective a range of interventions

are required. The interventions implemented should reflect both
the needs and resources of the organisation. Listen to Professor
Peter Davey discuss interventions to improve antibiotic
prescribing in hospitals by clicking here.
To provide the foundations for a successful ASP it is suggested

that core AMS interventions are implemented initially. Once the
ASP has been successfully established additional interventions
can be added as appropriate. Core and additional AMS
interventions as defined by the IDSA are shown in figure 8(2).

CORE ADDITIONAL
FORMULARY RESTRICTION WITH RE- DE-ESCALATION OF THERAPY BASED ON
AUTHORISATION OF NAMED ANTI- CULTURE RESULTS
INFECTIVES DOSE OPTIMISATION
PROSPECTIVE AUDIT WITH IV TO PO SWITCH
INTERVENTION AND FEEDBACK
EDUCATION
MULTIDISCIPLINARY AMS TEAM
ANTIMICROBIAL ORDER FORMS
GUIDELINE DEVELOPMENT
ANTIMICROBIAL CYCLING
COMBINATION ANTIMICROBIAL THERAPY
INFORMATION TECHNOLOGY TO
PROVIDE DECISION SUPPORT AND
ENHANCED SURVEILLANCE
ANTIBIOGRAMS - AT PATIENT AND
ORGANISATION LEVEL
FIGURE 8
Core and additional AMS interventions
CORE INTERVENTIONS
It is recommended that organisations choose either pre-
authorisation of restricted antimicrobial agents or prospective
audit and feedback, or a combination of both. These are
sometimes referred to as front-end and back-end strategies and
are discussed further in figure 9.
FRONT END (HOSPITAL) BACK END (WARD BASED)
• Antimicrobial policy • Antimicrobial review:

“rule book” commonly indication,
• Formulary and IVOS, TDM, allergy,
restriction C&S results, ADRs.
Less commonly:
• Guidelines or
bacteraemia, specific
pathways for treatment
AB, dose optimization.
and prophylaxis
• Audit and direct
• Protects broad-
feedback to
spectrum
prescribers
antimicrobials
• AMS team review FIGURE 9
when told. How pre-authorisation of restricted antimicrobial agents and
prospective audit and feedback can be used as part of an ASP(3).
Figure adapted from Chung GW et al. Virulence 2013;4(2):151–157

The advantages and disadvantages of pre-authorisation

of restricted antimicrobial agents or prospective audit and
feedback are discussed in table 1.
Pre-authorisation Prospective audit and feedback
Advantages
Increases visibility of ASP and helps to form professional

Prevents unnecessary/ inappropriate initiation of antibiotics
relationships
Ensures optimal empirical therapy Maintains autonomy of prescribers
Prompts review of clinical parameters, patient history and prior Frequency can be tailored based on resources available to the
cultures before initiating antimicrobial therapy ASP
Potential to decrease antibiotic expenditure Facilitates prescriber education
Facilitates a rapid response to antibiotic shortages Accommodates review of extended antimicrobial therapy
Allows for de-escalation of antibiotics once sensitivities

Gives Infection Team direct control over antibiotic use
available
Disadvantages
Has little effect post empirical therapy Compliance voluntary
Loss of prescriber autonomy Labour intensive
Success is dependent on how feedback is communicated to

May delay initiation of therapy
prescribers
Potential for variation in advice depending on the team

Can be difficult to de-escalate if patient is responding
member consulted
Real-time resource intensive IT support needed to identify patients to target
Potential for incorrect / omitted details in an attempt to bias

Reductions in targeted antibiotic use may not be immediate
antibiotic choice
TABLE 1
Comparison of pre-authorisation versus prospective audit and feedback of restricted antimicrobials(2)
AMS team members should have clearly defined roles and

responsibilities and receive adequate training and resources
to allow them to fulfil their duties. Often there will be much
overlap in roles between the core members of the AMS team.
Suggested roles for core AMS team members are included in
figure 10(1):

FIGURE 10
Suggested roles for core members of the AMS team. Images courtesy of Vishal Marotkar, IconTrack, Creative Stall and Jeff from Noun Project

GUIDELINE DEVELOPMENT • Specific confirmed

infections including:
Organisations should have comprehensive, evidence based
- Staphylococcus aureus
guidelines relevant to the local population freely available at
- Clostridium difficile
the point of prescribing. Antimicrobial agents should be chosen
- Tuberculosis
based on local microbiology and susceptibility patterns, with
guidelines reviewed annually with local antibiograms.
SA health has a comprehensive section on antimicrobial
Guidelines should include recommendations on antimicrobial guideline development which was developed by the South
agent, route, dose and duration. The UK Specialist Advisory Australian expert Advisory Group on Antimicrobial Resistance
Committee on Antimicrobial Resistance recommends a minimum (SAAGAR). This includes a guideline on the principles of
standard for empirical treatment guidelines and prophylaxis antimicrobial prescribing, a range of surgical prophylaxis
guidelines which are displayed in table 2. guidelines and guidelines for the prescribing and monitoring of
Table 2: UK Specialist Advisory Committee on Antimicrobial aminoglycosides and vancomycin.
Resistance minimum standards for empirical treatment
guidelines and prophylaxis guidelines(4)
ACCESS GUIDELINES
Empirical treatment Prophylaxis guidelines
guidelines
• Sepsis of unknown origin • Bacterial endocarditis
You may also find John Hopkins Medicine’s Antibiotic Guidelines
• Upper respiratory tract prophylaxis including
infections useful.
procedure-specific criteria
• Lower respiratory tract to identify which patients
infections including:
should be offered
- community acquired
pneumonia prophylaxis ACCESS GUIDELINES
- hospital acquired • Endoscopic procedures
pneumonia including procedure-
- exacerbations of specific criteria to identify
chronic obstructive These guidelines contain recommendations on formulary
pulmonary disease which high-risk patients
restriction, the treatment of specific organisms and infections,
• Urinary tract infections should be offered
allergy and therapeutic drug monitoring.
• Skin and soft tissue prophylaxis
infections including: Guidelines should include recommendations on documentation,
• Surgical prophylaxis
- cellulitis 48-72 hour review, and intravenous to oral switch. The principles
recommendations
- chronic ulcers of “Start Smart Then Focus” are a useful reference when
for common surgical
- necrotizing fasciitis developing antimicrobial guidelines.
interventions within the
- injuries or bites organisation including:
• Gastro-intestinal infections
- timing of initial dose
including:
- single dose where
START SMART THEN
- food poisoning
- intra-abdominal sepsis possible
FOCUS GUIDANCE
• Eye, ear, nose and throat - criteria for repeat doses
infections
• Splenectomy immunization Prescribing principles from “Start Smart Then Focus” for
• Central nervous system
infections including: and antimicrobial empirical therapy and surgical prophylaxis are shown are shown
- bacterial meningitis prophylaxis in figures 11 and 12 respectively.
- viral encephalitis
• Genital tract infections
• Blood stream infections
• Endocarditis

FIGURE 11
Prescribing principles for empirical antimicrobial therapy from “Start Smart Then Focus”
FIGURE 12
Prescribing principles for surgical prophylaxis from “Start Smart Then Focus”

ADDITIONAL INTERVENTIONS
De-escalation of therapy based on culture results AN INTRAVENOUS TO ORAL SWITCH
SHOULD BE CONSIDERED WHEN A
The need to take microbiology cultures where appropriate PATIENT MEETS ALL OF THE FOLLOWING
should be incorporated into empirical treatment guidelines. CRITERIA:
Antimicrobial prescriptions should be reviewed at 48-72 hours
• Temperature <38°C for the previous improving
and de-escalated to a narrow-spectrum agent or escalated in 24 hours
line with available microbiology culture and susceptibility results.
• Signs & symptoms of infection improved or resolved
The prescribing outcome should be documented in the medical
• Oral / nasogastric intake tolerated & absorbed
notes.
• No specific indication for prolonged intravenous
Electronic prescribing systems may be utilised to remind therapy e.g. meningitis, febrile neutropenia,
prescribers of the need for a review of antimicrobial therapy bacteraemia, endocarditis, osteomyelitis
at 48-72 hours and an alert for mismatches between • Availability of a suitable oral agent
microbiological culture results and antibiotic therapy may be
• Patient likely to be adherent with oral therapy
available.
- In children consideration needs to be given to
Dose optimisation the palatability of oral agents
Dose optimisation is needed to ensure antimicrobial therapy is

effective whilst minimising the possibility of adverse effects. FIGURE 14
Suggested criteria for switching antimicrobial therapy from the
Standard antimicrobial doses should be included in empirical
intravenous to oral route(1)
therapy guidelines and optimised according to renal function,
hepatic function, severity of infection and therapeutic drug
monitoring. Pharmacists are a key resource in dose optimisation, Education
especially in the interpretation of therapeutic drug monitoring
Education of healthcare professionals is a crucial part of an
and complicated pharmacokinetics.
effective antimicrobial stewardship programme. Unlike other
IV to PO switch medications where prescribing is restricted to specialists, for
Criteria for switching from intravenous to oral therapy should be example cytotoxic agents, antibiotics are widely prescribed by
readily available to prescribers. Oral prescribing should be used clinicians at all stages of their career, in many cases without
wherever possible. The benefits of oral prescribing are shown in regulation. Healthcare professionals should receive education
figure 13. Recommended intravenous to oral switch criteria are on induction and mandatory updates every 3 years(5). The
shown in figure 14. role of an antimicrobial stewardship programme within a wider
educational programme for healthcare professionals and the
general public is shown in figure 15 below(6).
BENEFITS OF ORAL PRESCRIBING

• lower treatment costs
• decreased nursing time
• reduced risk of infection from intravenous catheters
• reduced length of stay
• higher patient satisfaction
FIGURE 13
Benefits of prescribing oral antimicrobials(1)
FIGURE 15
How education of prescribers via curriculum and an ASP fits into
educational proposals for the wider population.

Continual education is key. In the United Kingdom (UK) it

is recommended that defined antimicrobial prescribing and
stewardship competencies are incorporated into appraisals for
prescribers. These competencies can also be used to inform
educational sessions for prescribers.
ACCESS THE ARHAI

AND STEWARDSHIP
COMPETENCIES FIGURE 16
Example of an antimicrobial section in a paper drug chart(7)
You can access a free online learning module by the University Antimicrobial cycling
of Dundee and British Society of Antimicrobial Chemotherapy
here: Antimicrobial cycling involves the substitution of some classes
of antimicrobials from use within an organisation for a defined
period of time. The original antimicrobial is then reintroduced at
a later date. The aim of this intervention is to limit the selection
ACCESS MODULE of antimicrobial resistance to the cycled antimicrobials. Although
early studies favoured this approach, subsequent mathematical
modelling studies suggest that antimicrobial cycling is unlikely to
be effective in the control of AMR.
The Stanford Center for Continuing Professional Education
provides a free online learning course on managing infections in Combination antimicrobial therapy
the outpatient setting.
Combination antimicrobial therapy, for example the addition of
an aminoglycoside to a beta-lactam, may be an effective way
of reducing the prescribing of broader-spectrum antimicrobials.
The inclusion of combination therapy in empirical guidelines
ACCESS LEARNING COURSE must be based on local susceptibility data. Recent national
susceptibility data in England has highlighted this as a useful
AMS intervention as shown in figure 17, click below to read the
Antimicrobial order forms full ESPAUR report.
Sections specifically may be built into paper drug charts to
encourage best practice when prescribing and reviewing
antimicrobial agents as shown in figure 16.
ESPAUR REPORT
UPDATING THE DRUG CHART
Click above to read about how updating the drug chart improved
antimicrobial stewardship at a large teaching hospital in England
FIGURE 17
Susceptibility of E. coli blood culture isolates within England to
combination therapy with co-amoxiclav and an aminoglycoside(8)

Information technology to provide decision support and

enhanced surveillance
Electronic decision support tools have a potential role in

assisting AMS programmes if they are integrated into prescribing
workflow. However the implementation of such systems is
resource intensive and requires the ongoing support of the AMS
team. Such systems could provide data useful for audit and
surveillance of antimicrobial consumption at both a patient and
organisational level.
In hospitals with electronic prescribing, order sets may be

incorporated into the system to promote adherence to guidelines
and increase convenience for prescribers. Prescriptions
generated from order sets can then be used to generate reports
for use in ASPs and audits.
Mobile apps are now common and can be useful for providing
antibiotic guidelines at the point of care. There is also an
opportunity to include educational messages or specialist
prescribing information such as safety of antibiotics in pregnancy
and breastfeeding. Dose calculators can be included for
antimicrobials with a narrow therapeutic window. However there
is a need for patient education as to why clinicians need to use
mobile devices at the bedside.
Some apps are Trust specific whilst others are designed to use
across wider areas such as that provided by NHS Scotland which
is illustrated in figure 18.
Surveillance
Surveillance structures should be in place at local and national

levels to assess antimicrobial usage and AMR over time; data
can be used to inform ASPs. Surveillance can improve outcomes
at local, national and global levels as is shown in figure 19.
FIGURE 18
An example of an antimicrobial app used within NHS Scotland
LISTEN TO DR ARJUN
SRINIVASAN DISCUSSING HIS
WORK USING SURVEILLANCE
TO IMPROVE ANTIBIOTIC
PRESCRIBING PRACTICES
LISTEN

33
HOW SURVEILLANCE CAN IMPROVE

HEALTH OUTCOMES
Globally
Provide early warnings of emerging
threats and data to identify and act
on long-term trends
Nationally
Guide policy and ensure
appropriate and timely
public health interventions
Locally
Allow healthcare
professionals to make
better informed clinical
decisions to ensure
better patient
outcomes
FIGURE 19
How surveillance can improve health outcomes. Image courtesy of Review on Antimicrobial Resistance(9)

The CDC recommends the use of DOTs in preference to

DDDs to measure antimicrobial consumption. However many
organisations do not have the ability to capture DOTs and DDDs
are used in surveillance, including in the UK. Antimicrobial
usage data and AMR are reported nationally in many countries,
with the ability to generate reports to benchmark against similar
institutions:
NAUSP:
Reports antimicrobial use and AMR in Australian hospitals on a
bimonthly basis. Australian hospitals can register here.
REGISTER
FIGURE 21
PHE fingertips: AMR data on Klebsiella pneumoniae from Thailand
Reports on AMR, antibiotic consumption, healthcare associated
infection rates, infection prevention and control and antimicrobial
stewardship in English primary and secondary care as shown in
figure 20. Click below to access the data.
HOW DO I ASSESS THE EFFECTIVENESS

OF AN ANTIMICROBIAL STEWARDSHIP
ACCESS DATA PROGRAMME?
There are many ways to assess the effectiveness of an ASP,
including:
• Audit of compliance with guidelines
• Audit documentation – e.g. indication, stop/review date,

48-72 hour review
• Audit time to 1st dose of antibiotic in sepsis
• Monitor antibiotic consumption data, including benchmarking

to similar institutions
• Monitor antibiotic expenditure data
• Monitor stewardship interventions and acceptance rates
FIGURE 20 • Review adverse events in relation to antimicrobials

PHE fingertips AMR local indicators
Defined outcome measures should be defined as part of an
organisations ASP strategy. Metrics that can be used to evaluate
CDDEP: interventions made as part of an ASP in patients with specific
Allows global comparison of AMR and antimicrobial consumption infectious syndromes are shown in figure 22.
from contributing countries as shown in the example in figure
21. Allows for comparisons between countries. Access the data
below.
ACCESS DATA

FIGURE 22
Metrics that can be used to evaluate
interventions made as part of an ASP(10)(1)
Point prevalence surveys
Local point prevalence surveys (PPS) are recommended on a

bi-annual or annual basis(5) as a tool to assess compliance with
antimicrobial guidelines. Results of PPS should be shared with
the executive team and disseminated to specialities who are
responsible for developing action plans within their area. Key
metrics which should be included in PPS are shown in figure 23.
Learn more about Point Prevalence surveys by taking the

“Challenges in Antibiotic Resistance: Point Prevalence Surveys”
course from Future Learn and BSAC.
ACCESS COURSE
FIGURE 23
Suggested key metrics for PPS

Organisations should be encouraged to take part in national and Some useful infographics which could be adapted locally can be
global PPS surveys to provide data on variation in prescribing found on the NCAS website.
practice and AMR. Further information on such studies is
available:
VIEW INFOGRAPHICS
ECDC PPS STUDY
See figure 25 for an example from New Zealand where
educational messages are given about an antibiotic or class of
antibiotics on a monthly basis.
COMMUNICATION
Within an ASP there are a number of key areas which will need
to be disseminated to staff, for example ASP vision, updates
to guidelines, PPS results, AMR rates, infection outbreaks and
antimicrobial shortages.
Routes of communication to all staff members within the

organisation must be established within an ASP. When planning
communication the proposed audience must be considered;
what works in one setting may not work in another. Proposed
communication routes are suggested in figure 24.
PROPOSED COMMUNICATION ROUTES

• Posters in clinical areas / staffrooms
• Use of hospital intranet
• Organisational newsletter
• AMS newsletter
• Hospital-wide email
• Notifications via electronic prescribing programme
or app
• Discussion at relevant hospital committees
• Screensaver / background on computers within the
organisation
• Email to divisional leads for dissemination in clinical
areas
• Social media
FIGURE 24
Suggested communication routes which may be used within an ASP
FIGURE 25
Antibiotic of the month newsletter (courtesy of Chris Little, Capital and
Coast District Health Board and Emma Henderson, Hutt Valley District
Health Board, New Zealand)

References:
1. Duguid, M; Cruickshank M. Antimicrobial stewardship in Australian hospitals. Sydney; 2011.
2. Dellit T, Owens R, McGowan J, Gerding D, Weinstein R, Burke J et al. Infectious Diseases Society of America and the Society for
Healthcare Epidemiology of America Guidelines for Developing an Institutional Program to Enhance Antimicrobial Stewardship.
Clin Infect Dis. 2007;44(2):159–77.
3. Chung, GW; Wu, JW; Yeo, CL; Chan, D; Hsu L. Antimicrobial Stewardship. Virulence. 2013;4(2):151–7.
4. Specialist Advisory Committee on Antimicrobial Resistance. Specialist Advisory Committee on Antimicrobial Resistance (SACAR)
Antimicrobial Framework. J Antimicrob Chemother. 2007;60(suppl_1):i87–90.
5. Public Health England. Start Smart - Then Focus Antimicrobial Stewardship Toolkit for English Hospitals [Internet]. 2015 [cited 2017
Apr 3]. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/417032/Start_Smart_Then_
Focus_FINAL.PDF
6. Lee, CR; Lee, JH; Kang, LW; Jeong, BC; Lee S. Educational effectiveness, target, and content for prudent antibiotic use. Biomed Res
Int. 2015;Epub 2015.
7. King, D; Jabbar, A; Charani, E; Bicknell, C; Wu, Z; Miller, G; Gilchrist, M; Vlaev, I; Dean Franklin, B; Darzi A. Redesigning the
“choice architecture” of hospital prescription charts: a mixed methods study incorporating in situ simulation testing. BMJ Open.
2014;4(e005473).
8. Public Health England. English surveillance programme for antimicrobial utilisation and resistance (ESPAUR) [Internet]. 2016 [cited
2017 Jun 27]. Available from: https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/575626/ESPAUR_
Report_2016.pdf
9. O’Neill J. Review on Antimicrobial Resistance [Internet]. 2016 [cited 2017 Jun 20]. Available from: https://amr-review.org/
10. Barlam, TF; Cosgrove, SE; Abbo, LM; MacDougall, C; Schuetz, AS; Septimus, EJ et al. Implementing an Antibiotic Stewardship
Program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America.
Clin Infect Dis.
11. Howard P., et al. An international cross sectional survey of antimicrobial stewardship programmes in hospitals. J Antimicrob
Chemother 2015; 70: 1245–1255

CHAPTER 10
AUTHOR: WILLIAM MALCOLM
WHAT IS MEASUREMENT
AND WHY IS IT IMPORTANT?
LEARNING OUTCOMES
CHAPTER IS TO: • Outline why measurement is a core element of antimicrobial stewardship programmes.
Outline the importance of • Define and explain the differences between quantitative and qualitative measurement
measurement within of antibiotic use.
antimicrobial stewardship • Explain the advantages, disadvantages and alternatives to defined daily doses as a
programmes. measure of antibiotic use.
Describe the main types of • List the types of data collected in point prevalence surveys.
measures used in surveillance • Give examples of ways information on antibiotic use can be presented and shared to
of antimicrobial use drive improvement.
programmes. • Reflect on how to apply learning from this chapter to their own practice.
Outline the importance of
sharing data with clinicians.
Measurement is part of our everyday lives. Have you ever thought am I gaining or losing
THE CHAPTER WILL weight or is my child getting taller? The only way to find out the answer is to measure
ALSO DEFINE: something. In these examples you would measure your weight or the child’s height. In any
antimicrobial stewardship programme, one of the key components will be the measurement
The concept of defined daily of antimicrobial use with antibiotics being the commonest agents used. We use this term
doses (DDD) as a measure through this chapter.
of antibiotic use quantity.
A dictionary definition of measurement is:
“
The use of point prevalence
surveys (PPS) to provide
information on qualitative
use of antibiotics.
The act or process of
The concept of data
visualisation to maximise
ascertaining the extent,
the impact of data on
antibiotic use.
dimensions, or quantity
of something

CHAPTER 10 - WHAT IS MEASUREMENT AND WHY IS IT IMPORTANT?
Lord Kelvin was a famous mathematician and physicist. He is The most important quote attributed to Kelvin on
“
best remembered for having the absolute temperature scale measurement is:
- the Kelvin scale-- named in his honour. Kelvin died before Sir
Alexander Fleming made his miraculous discovery of penicillin. If you cannot measure it,
So what has Kelvin to do with antimicrobial stewardship?
The answer is that Kelvin knew about the importance of you cannot improve it
measurement. Kelvin said:
The principle that you need to understand the baseline - the
point from which you're starting - in order to know if you are
improving is now a fundamental part of improvement science
and as stewardship is quality improvement based, this principle
is fundamental to antimicrobial stewardship programmes.
TAKE A FEW MINUTES TO CONSIDER THE WAY

ANTIBIOTICS ARE USED IN THE CLINICAL AREA
WHERE YOU WORK. WHAT DO YOU KNOW?
“
IS ANTIBIOTIC USE INCREASING OR
DECREASING?
To measure is to know ARE THERE ANTIBIOTIC PRESCRIBING POLICIES
IN PLACE?
What Kelvin meant is how can we possibly know something,
unless we measure it? In terms of antibiotic use: How can we IF SO, HOW WELL DO YOU FOLLOW THEM?
possibly know about antibiotic prescribing unless we measure it?
HOW WELL DO OTHER PRESCRIBERS FOLLOW
On the importance of measurement Kelvin went further when THEM?
he said:
“
The only way to determine if antibiotic use is improving is
When you can measure through measurement. Measurement firstly to set the baseline
something and express and then repeated measurement to check if things are
improving. As Kelvin said, "To measure is to know."
it in numbers, you know The next chapter in this e-book will consider in detail the quality
improvement approach to antimicrobial stewardship and will
something about it. reinforce the importance of measurement. When measurement
But when you cannot is being planned consideration needs to be given to the specific
reason for collecting data as this will inform the type and quality
express it in numbers, of data to be collected.
your knowledge is So in antimicrobial stewardship programmes there are three

main types of measures:
of a meagre and • Quantity of antimicrobial use
unsatisfactory kind • Quality of antimicrobial use
• Antimicrobial stewardship measures
The rest of this chapter will look at quantitative and qualitative

measurement of antimicrobial use. The use of structure, process
and outcome measures will be considered in more detail in
chapter 11.

QUANTITY OF ANTIMICROBIAL USE that antibiotic.
If your hospital has electronic prescribing of medicines, In summary, front line clinicians are unlikely to use DDDs as they
data on antibiotic use will be available in the information are not useful for informing the clinical care of individual patients.
system. In the many hospitals without electronic prescribing However, DDDs are a commonly used standardised metric in
the hospital pharmacy system can provide information on surveillance programmes. A metric is a quantifiable measure
antimicrobials supplied to wards and other clinical areas. that is used to track and assess the status of a specific process,
These data can be used as a proxy for antimicrobials given to in this case quantity of antibiotic prescribing. Antibiotic use
patients. In the community data on antimicrobial use may come expressed in DDDs enables comparison of patterns of antibiotic
from medicine sales data or from national medicines use over time, between locations and after improvement
use surveillance programmes. interventions, thereby identifying areas for further investigation
using audit and quality improvement methods.
Introducing defined daily doses (DDDs) as a measure
Are DDDs a perfect measure of antibiotic use in stewardship
Clinicians involved in prescribing, supplying or administering
programmes?
antibiotics will be familiar with their doses. However, within
an antimicrobial stewardship programme, when it comes to DDDs were never developed specifically to monitor the impact
measuring and expressing antibiotic use in numerical terms of antimicrobial stewardship interventions. It is not a perfect
(remembering Kelvin’s wise words!) a standardised measure is measure. The table below shows some advantages and
required. The most common, standardised measure is defined disadvantages of DDD as a metric.
daily doses (DDD). The World Health Organisation (WHO) has
What are alternatives to DDDS?
assigned DDDs to antibiotics.
An alternative is the Days of Therapy (DOT). One DOT represents
the administration of a single antibiotic on a given day regardless
of the number of doses administered or dosage strength e.g
VISIT WHO SITE ON DDD administration of cefuroxime as a single 1.5g dose or as three
750mg doses eight hours apart would both represent 1.0 DOT.
The use of DOT may overcome some of the disadvantages of
DDDs. The main disadvantage is they are relatively more difficult
The basic definition for a DDD is the:
to measure as they require patient level information.
Assumed average maintenance dose Other ways of expressing antibiotic use are:
per day for a drug used for its main Prescribed Daily Dose - The Prescribed Daily Dose (PDD) can
indication in adults be determined from prescription studies, medical or pharmacy
records and patient interviews. It is important to relate the PDD
In simple terms, the DDD is the amount of antibiotic that a typical
to the infection for which the antibiotic is required. There can
adult patient will receive each day for treatment of an infection.
be differences in the PDD between countries based on national
Remember the DDD is a technical measurement - a dose used to
treatment guidelines.
measure drug use. It is not a clinical dose. The DDD calculated
by the WHO is often a compromise based upon information on Number of prescription items – In community settings the
doses used in different countries and it often differs from those number of prescription items dispensed may be used. These
doses recommended for clinical use because the doses for data will give an indication of the number of times antibiotics
individual patients will be based on patient characteristics, such were used.
as age, weight, and pharmacokinetic considerations, such as
Cost - These data are easy to obtain and are generally easily
renal function.
understood by administrators but price differences between
DDDs are used for monitoring trends of antibiotic use over time different products and changes over time limit their usefulness.
(e.g. is use going up or down) in a ward, hospital or group of
Volume - Common physical units such as grams are easy to
hospitals. This is called ‘surveillance of antibiotic use’. DDD
obtain and can be used to produce DDD.
measurements may be undertaken on a monthly or quarterly
basis depending on the setting and the antibiotics included. To The importance of a denominator
calculate the total DDDs for a period, the total number of grams When measuring antibiotic use it is helpful to review the raw
of each antibiotic used in a ward (or whole hospital) during a DDD data to get an indication of whether it is changing over
defined period is divided by the WHO assigned DDD value for time. In simple terms plot the dots and see what is going on i.e.

ADVANTAGES DISADVANTAGES
INTERNATIONALLY RECOGNISED AS ASSIGNED UNSUITABLE FOR PAEDIATRIC SETTINGS

AND PUBLISHED BY WHO. AS DDD DEFINED AS AVERAGE DOSE
IN ADULTS.
ONCE SET BY WHO A DDD IS NOT OFTEN

CAN OVER OR UNDERESTIMATE ANTIBIOTIC
CHANGED - THIS ALLOWS ASSESSMENT OF
USE AS DO NOT ACCOUNT FOR ALTERNATIVE
PRESCRIBING OVER TIME.
DOSING REGIMES DUE TO RENAL
DYSFUNCTION, OBESITY ETC.
EASY TO PRODUCE INFORMATION ON

ANTIBIOTIC USE EXPRESSED IN DDD FOR BIAS AGAINST COMBINATION THERAPY - USE
WARD, UNIT OR HOSPITAL. OF THREE NARROW SPECTRUM ANTIBIOTICS
RATHER THAN ONE BROAD SPECTRUM
ANTIBIOTIC WILL RESULT IN THREE TIMES
AS MANY DDD BEING USED FOR THE SAME
INFECTION.
ABILITY TO COMPARE ANTIBIOTIC USE IN MAY NOT REFLECT DOSE USED FOR
A STANDARDISED WAY BETWEEN WARDS, A PARTICULAR INFECTION.
HOSPITALS, REGIONS OR COUNTRIES
is use increasing or decreasing? The quantitative measurement

of antibiotic use is usually presented as a rate with the number of
DDD as the numerator and a denominator that takes account of
VIEW IMPLEMENTING AN
changes in the population of interest over time. A denominator ANTIBIOTIC STEWARDSHIP
will be needed to enable the measurement of use over time ARTICLE
and between geographical regions such as hospitals, regions or
countries to become meaningful.
In the community setting the simplest denominator is the

number of inhabitants in the population. The most common VIEW GUIDELINES FOR
measure is DDD per 1000 inhabitants per day (often called DEVELOPING AN INSTITUTIONAL
DID). Other more complex denominators may take into account
characteristics of the population such as age and gender and
PROGRAM TO ENHANCE
relative comorbidity.
In hospitals changes in the patient census may impact on
ARTICLE
the quantity of antimicrobial use. Normalising antibiotic use
and presenting it as a rate will help account for fluctuations
in hospital activity such as the number of patients in hospital When comparing antibiotic use between hospitals also
and their length of stay. One of the most commonly used remember that total antibiotic use defined as DDD will be
denominators in hospital programmes is the number of patient influenced by specialty mix within and between hospitals:
days or occupied bed days. This requires information on bed hospitals with specialist units such as intensive care units
utilisation. The landmark guidance on antimicrobial stewardship may have higher use of antibiotics than a local
non-specialised hospital.
by the Infectious Disease Society of America and Society for
Healthcare Epidemiology of America recommends DDD/1000
patient days as a metric for hospital based antimicrobial
stewardship programmes.

A common definition for point prevalence is the amount of

people with a particular characteristic at a certain point in
SO DESPITE THE INHERENT time. It is determined by taking the total of the people with the
DISADVANTAGES, THE DDD characteristic divided by the total of people in the population of
HAS BECOME ESTABLISHED interest. So a PPS of antibiotic use will measure the number of
people taking antibiotics at a given point in time.
AS THE COMMON,
Why undertake a PPS?
STANDARDISED METRIC
• Identify and monitor rates of antibiotic prescribing in
FOR THE SURVEILLANCE OF hospitalised patients (adults, children and neonates)
ANTIBIOTIC USE. • Identify differences between prescribing rates between
hospital departments, hospitals, regions and countries
HOWEVER, DDDS WILL
• Determine veriation in antibiotics, dose and indication
NOT TELL THE WHOLE across different locations
STORY, OTHER TYPES Depending on the way the PPS is set up and the data collected
OF MEASUREMENT ARE there can be wealth of information:
NEEDED....... • Use of board or narrow spectrum antibiotics
• Indications for antibiotics - community or hospital acquired

infections, medical or surgical prophylaxis
QUALITY OF ANTIMICROBIAL USE • Which antibiotics are being used for particular infections?
The key disadvantage of the quantitative approach is whether it • Are they prescribed in line with local guidelines?
really reflects the quality of antibiotic prescribing. A quantitative • What is the duration of antibiotics for surgical prophylaxis?
approach will tell you about the volume of total antibiotic use or
• Has a clear duration of treatment or stop date been recorded?
of particular antibiotics; is it increasing or decreasing, but does
this really reflect the quality of antibiotic prescribing? • Has the treatment been changed in light of microbiology
results?
A qualitative approach is required to provide information
on which patients are being given which antibiotics, their Furthermore, PPS can help to identify targets for quality
indication, which antibiotics are being used for treatment of improvement in antibiotic prescribing, identify interventions
particular infections and whether the antibiotics prescribed are to promote better stewardship of antibiotics to assist the fight
in accordance with local prescribing guidelines. Remembering against antimicrobial resistance and assess the effectiveness of
the principle that we need to measure to improve, then, the use interventions through repeated surveys.
of Point Prevalence Surveys (PPS) enables assessment of the
quality of antibiotic use and identification of targets for quality
What data needs to be collected in a PPS?
improvement. Electronic prescribing and routine data linkage
Ward or denominator data
is not available in most hospitals and so PPS has become a key
approach to planning and assessing the impact of antimicrobial This will be information about the ward in which the PPS is being
stewardship interventions. A good course for those interested undertaken, including the type of ward, the number of patients
in learning more about this is available: present on the study day.
VIEW PPS COURSE

Patient or numerator data benefits of the Global-PPS from Ann Versporten, Global-PPS
coordinator, University of Antwerp, Belgium
For each patient prescribed any of the specified antimicrobials
the following types of data will be recorded:
DATA ELEMENT DATA OPTIONS WHY NOT TRY USING THE GLOBAL PPS FORM
Name of drug From filtered WHO Drug List TO COLLECT DATA ON A SINGLE PATIENT (PAGE
3) OR YOUR WARD (PAGE 2) TO HELP YOU, HAVE
Route Parenteral, Oral, Rectal, Inhalation
A LOOK AT AN EXAMPLE OF A COMPLETED FORM
Unit dose Grams or NU, to three decimal places
TO HELP YOU GET STARTED.
Dosage frequency 1-12 per day, every (18, 36, 48) hours,
twice per week, three times per week, IF YOU HAVE NOT PARTICIPATED IN A PPS
continuous infusion BEFORE YOU MAY FIND IT USEFUL TO TRY
Indication Coded list of indications COLLECTING DATA FOR A FEW PATIENTS TO SEE
HOW IT FEELS TO COLLECT THIS DATA OR YOU
Indication group Indication group
COULD COLLECT DATA FOR ALL PATIENTS IN
Prophylaxis Surgical, medical
YOUR WARD. IT MAY LOOK LIKE A LARGE TASK
Diagnosis Coded list of diagnosis TO COLLECT THIS DATA SET FOR ALL PATIENTS
Day of therapy 1-28, 29+, Long Term, Unknown ON ANTIBIOTICS, BUT SEVERAL STUDIES FROM
Is Review/Stop y/n/unknown VARIOUS COUNTRIES HAVE SHOWN THAT ON
date documented AVERAGE ONE-THIRD OF PATIENTS IN A WARD
Reason in notes y/n/unknown WILL BE PRESCRIBED AN ANTIBIOTIC ON A
GIVEN DAY. SO THAT MEANS, FOR A 30-BEDDED
Complies with y/n/unknown
WARD, THERE WILL BE TEN PATIENTS RECEIVING
(local) guidelines
AN ANTIBIOTIC FOR WHOM YOU WOULD
Date start DD/MM/YY (the date fir antimicrobial was
COLLECT DATA
indication prescribed for indication)
Examples of PPS tools Are you now thinking about collecting data in your own setting?
The use of PPS within local or national antimicrobial stewardship Watch this presentation which outlines the factors you will need
or surveillance programmes has become more common to consider when planning for a PPS for the first time. Most of
in recent years. Between 2006 and 2009, the European these will be relevant whether you are planning a small-scale
Surveillance of Antimicrobial Consumption (ESAC) programme survey in a small number of wards or a hospital-wide PPS.
developed a standardised PPS dataset. In 2011, ESAC was PPS is a well-established stewardship tool in some parts of the
integrated into the work of the European Centre for Disease world, but in other countries clinicians have just begun to explore
Prevention and Control (ECDC). The dataset used by ESAC was how to use PPS. Read testimonials from clinicians from around
adapted for a combined PPS on healthcare associated infection the world who have undertaken a PPS:
and antimicrobial use in 2011 and 2016. More information on this
ECDC Point Prevalence Survey in European acute care hospitals
is available here. Australia
Antimicrobial resistance is a global problem. Therefore, the
India
Global PPS of Antimicrobial Consumption and Resistance
has been developed. The Global-PPS is an ambitious project
Japan
collecting data at a global level to monitor rates and quality
of antimicrobial prescribing combined with microbiology and Malta
resistance data in hospitalised patients. It has established a
global network for PPS and aims to include as many hospitals Singapore
from as many countries from all continents. The Global-PPS
creates global awareness about antibiotic use and resistance South Africa
and will be instrumental in planning and supporting national
and local stewardship interventions in a range of resource and USA
geographical settings. Watch this presentation on the aims and

USING DATA TO IMPROVE To encourage a whole team approach it is beneficial to share

ANTIMICROBIAL STEWARDSHIP data at multi-professional meetings and this can be done
informally at ward meetings or via hospital or directorate level
The how and why of measurement in antimicrobial stewardship
audit meetings or in a community setting with all staff in a clinic.
is important but more important is that once you have gone to
It is useful to show comparisons with peers (e.g. between wards
the effort to collect and analyse the data that you use it, that
within the same hospital or with other nearby hospitals as useful
you share it with front-line clinicians to enable them to reflect on
enabler to facilitate change. Similarly identifying outliers is also
their practice and change their prescribing behaviour to improve
a useful technique. When providing a benchmark it is important
patient outcomes and minimise resistance and other harm.
that the benchmark is meaningful. A useful benchmark is to
It is important to share data in as near real time as possible. use the ‘best in class’ approach which recognizes that variation
Timely feedback of data means that it is more likely that the exists and sets the target at the 25th percentile i.e. the level of
clinicians seeing the data were responsible through their performance that the best quarter of prescribers can achieve.
prescribing behaviours for the results. Engagement with
It is always important to highlight success as well as identify
clinicians is crucial to change their prescribing behaviours.
areas for improvement and encourage discussion of how
Quantitative and qualitative data can be feedback in a variety of changing ward processes may help to improve prescribing.
ways. The method will be driven by the intended audience and Common methods of sharing data are published reports,
whether the data are being used for improvement, accountability benchmarking and run charts.
or research.
Here are some examples of the ways antibiotic use data can
be presented.
This example from Denmark

shows the change in use of
different antibiotic groups at
national level over a 10 year
period.
Here is an example of
a report issued to GP
practices in Scotland which
shows their prescribing data
versus benchmarks. These
benchmarks are the 25th
percentile i.e. the antibiotic
prescribing rate achieved
or bettered by the quarter
of practices with the lowest
prescribing rate in the local
NHS board and across
Scotland as a whole.

The figure below is taken from the national PPS of healthcare

associated infection and antimicrobial prescribing 2016
published by Health Protection Scotland and shows how the
prevalence of antibiotic prescribing varied by specialty. The
highest prevalence of patients receiving one or more antibiotics
was reported in intensive care patients. –figure 20
WHAT ABOUT DATA VISUALISATION? clinicians who may be reluctant to read detailed text heavy
reports.
A priority for antimicrobial stewardship programmes is to
support learning health systems through maximising the A good example of data visualisation and benchmarking is
use of current and emerging data. For the data to have its the use of AMR indicators within the Fingertips application
greatest impact it must be easily accessible, visualised well developed by Public Health England. This system presents
and meaningful to clinicians and mangers. The information information in a publicly accessible website showing data on
will then be a catalyst for quality improvement by enabling AMR indicators which can be viewed in format selected by
continuous monitoring of the impact of infection prevention the user which show temporal trends and comparison with
and treatment interventions on antibiotic use together with benchmarks.
intended and unintended patient outcomes. When producing published reports the use of data visualisation
Data visualisation is the presentation of data in a pictorial or techniques are also being employed more frequently to
graphical format. It enables decision makers to see analytics summarise the key information.
presented visually, so they can grasp difficult concepts or identify
new patterns. It is increasing being used to feedback data to

Here is an example of an infograph showing antimicrobial use in

European hospitals produced by ECDC from PPS data.
In summary measurement important. Think about what data

you need, who and how it will be collected, how the data will be
used to generate intelligence and most importantly how it will be
quickly fed back to drive improvement.
To measure is to know

CHAPTER 11
AUTHOR: JACQUELINE SNEDDON
METHODS FOR IMPROVING

THE QUALITY OF
USING LOCAL DATA
LEARNING OUTCOMES
CHAPTER IS TO:
• List some quick wins to improve antimicrobial use
Describe the simple • Outline how a quality improvement approach can be applied to antimicrobial use
interventions that can
• Identify suitable formats for sharing data with various audiences
improve antimicrobial use
within a ward or hospital. • Reflect on how to apply learning from this chapter to their own setting
Outline the improvement

methodologies that can
INTRODUCTION
support stewardship.
The previous chapter covered why measurement is important within any stewardship
Describe the types of programme and how both quantitative and qualitative measurement can be used to provide
measures that can be used useful information about antimicrobial use within a hospital. While this type of information is
and their utility. extremely useful it cannot provide sufficient detail about the prescribing process to identify
where changes can be made to improve clinical practice. Small scale data collection at
Outline methods of
individual ward level can be used to inform improvements in practice through changing
feeding back data to drive
behaviours of clinical staff. Various interventions based on audit of clinical practice can
improvements in practice.
be easily achieved in any setting without the need for complex IT systems. Common
methodologies include prospective audit and feedback, various quality improvement
THE CHAPTER WILL
approaches and systems to restrict the use of specific antibiotics. Collecting, analysing
ALSO DEFINE:
and most importantly sharing data from these interventions can drive improvements in
The model for improvement prescribing behaviours, increase compliance with local policies and ultimately optimise
and PDSA cycles. antibiotic therapy at individual patient level. This chapter will consider the evidence
supporting various interventions, provide practical advice on using various methodologies
Goals for quality improvement
and also provide information about models for planning interventions as well as measures
interventions.
for evaluating the outcomes of interventions.
Concepts behind action Some new concepts and terminology that will be considered include:
and evaluation planning.

CHAPTER 11 - METHODS FOR IMPROVING THE QUALITY OF ANTIMICROBIAL PRESCRIBING USING LOCAL DATA
ACTIVITIES TO
LOW HANGING FRUIT THE MODEL FOR IMPROVEMENT
CHANGE PRACTICE
TOOLS FOR
DRIVER DIAGRAMS DOUBLE DIAMOND MODEL
IMPROVEMENT
STRUCTURE, PROCESS,
WAYS TO ASSESS
CONTRIBUTION ANALYSIS OUTCOME (INCLUDING
BALANCING) MEASURES CHANGES MADE
GETTING STARTED WITH IMPROVING Prospective audit and feedback of data collected on antibiotic
ANTIMICROBIAL PRESCRIBING prescribing targeted at wards or problem areas of practice is
also useful as a quick win. An example of this type of approach
When resources are scarce or when you require to demonstrate
is shown in a study from Canada. Audit and Feedback to Reduce
that a new project or idea will deliver benefits that have a
Broad-Spectrum Antibiotic Use among Intensive Care Unit.
positive impact on patient care it is often helpful to target
‘quick wins’. This means that with a small amount of effort over Data from antimicrobial consumption or from point prevalence
a short period of time something truly useful can be achieved. surveys can be used to identify areas for improvement. These
By using this approach investment in a programme of work can then be captured in a simple audit form (see example below)
can be secured or it can be used to generate enthusiasm that can be used to look at issues in more detail.
amongst fellow clinicians to get involved. Interventions that
Patient ID
provide quick wins often involve targeting things that are easy
Name of drug
to achieve referred to as ‘low hanging fruit’. Low Hanging Fruit
is a metaphor commonly used for undertaking the easiest and Route
simpler tasks first and is based on the concept that when farmers Unit dose
are harvesting fruit or when animals are grazing on fruit they Dosage frequency
would tend to take the low hanging fruit first as it is easiest Indication
to reach. There are good examples from the literature about
Complies with
targeting low hanging fruit to achieve success in stewardship
(local) guidance
programmes. Initiatives including intravenous-to-oral switch,
batching of intravenous antimicrobials, therapeutic substitution, Such an initiative utilising audit and feedback across hospitals
and formulary restriction, can result in early successes and in South Africa delivered improvements in several aspects of
significant cost savings. antimicrobial prescribing. This involved pharmacists used 5
targeted measures to inform interventions to improve both the
quality and quantity of antibiotic use.
VIEW LOW HANGING

FRUIT ARTICLE
VIEW DOCUMENT

QUALITY IMPROVEMENT (QI) APPROACH Duration Short period of Medium – long Can take
time – weeks, duration long
Introduction to QI
months Longitudinal trends periods
The use of quality improvement methodology within healthcare Small ‘tests and historic data of time to
has expanded rapidly over the past ten years. This started in of change’ obtain
the United States with several healthcare providers addressing accelerates results
deficiencies in their systems which were leading to high litigation the rate of
costs, supported by the Institute for Healthcare Improvement improvement
(IHI).
Analysis Run charts League tables/ Traditional

or statistical benchmarking statistical
VISIT IHI SITE process achievement of tests
control charts target
Quality improvement in healthcare is now widespread across

Europe, North America, Canada, Australia and is emerging as a Quality improvement methodology involves changing practice
valuable tool in lower and middle income countries. Much of the and there are 3 elements which are necessary for improvement
experience and the tools used in quality improvement originated to be successful:
in the manufacturing and aviation industries which have radically
improved safety during the past 25 years.
NECESSARY FOR IMPROVEMENT
Before starting to collect data within a clinical setting it is TO BE SUCCESSFUL
important to think carefully about the specific reasons for
collecting it as this will inform the type and quantity of data to
collect.
There are 3 reasons for collecting data:
• Research to generate evidence WILL TO CHANGE

• Accountability - judgement or scrutiny of performance CONVINCING PEOPLE THAT CHANGE IS BENEFICIAL
• Quality improvement
This table compares the important factors in deciding which type

of data we need:
IMPROVEMENT ACCOUNTABILITY RESEARCH

Purpose Understanding Comparison To discover IDEAS TO EFFECT CHANGE
of Process Reassurance new
HOW TO MAKE PROCESSES AND OUTCOMES BETTER
Evaluation of knowledge
change
To bring new
knowledge into
daily practice
Data Gather just Large amounts of Gather as
EXECUTION OF THE IDEAS
enough data data on ongoing much data
to learn and basis as possible TOOLS AND TECHNIQUES ALONG WITH THE
complete ‘just in CAPACITY AND CAPABILITY AMONGST STAFF WHO
another cycle case’ WILL PUT THE IDEAS INTO PRACTICE

Applying QI to antimicrobial stewardship what is happening and these are usually process measures
which are easy to collect.
QI interventions within infection management are typically
directed at managing invasive medical devices and increasing If trying to improve compliance with the local antibiotic policy
compliance with local policies for infection control and within a ward some potential process measures that could be
antimicrobial prescribing. There are several quality improvement collected daily over a short time period might be:
methodologies used in healthcare e.g. the Model for
• How many of the clinical staff on the unit/ward are aware
Improvement, LEAN, Six Sigma but all use similar components.
of the local antibiotic policy and able to access it at the point
of care?
VIEW QUALITY IMPROVEMENT •

How many patients have received the correct antibiotic as
specified in the local policy?
APPROACHES ARTICLE
However, outcome measures which measure the impact of
changes on patients are more valuable but also more difficult to
The Model for Improvement provides a simple yet powerful collect e.g. Are the policy antibiotics effectively treating a specific
tool for accelerating improvement based on three fundamental infection? – clinical cure rate/ mortality/ ICU admission.
questions:
In the following example the Model for improvement and
• What are we trying to achieve? A clear aim – what, how a PDSA cycle is applied to a common scenario in clinical
much, by when? practice: a recent audit has identified that patients undergoing
• How will we know that change is an improvement? Measuring vascular surgery received a range of antibiotics as surgical
processes and outcomes prophylaxis and in many cases antibiotic choice did not follow
• What changes can we make that will result in an the local policy.
improvement? What do we want to test? What can we learn
as we go along? AIM Within 2 weeks all patients undergoing vascular
surgery will receive the correct antibiotic for
The Model uses PDSA (PLAN, DO, STUDY, ACT) cycles to test surgical prophylaxis as defined in the local
changes which may result in improvement. It is useful to consider policy.
PDSA as an ongoing process as shown in this diagram. MEASURES Availability of antibiotic policy in vascular surgery
ward and in all theatres where vascular surgery
is performed.
Plan Ward staff, surgeons, anaesthetists and other
Act • Objective theatre staff aware of antibiotic policy and can
• Ready to • Questions &
access it.
implement? predictions
Adequate stock of the policy antibiotic is
• Try something • Plan to carry out:
available in all theatres used for vascular
surgery.
else? Who?When? Patients undergoing vascular surgery are
• Next cycle How? Where? prescribed and administered the policy antibiotic
at the correct time prior to the procedure.
Study Do TESTS Display/locate policy in ward and all relevant
• Complete data • Carry out plan theatre areas and check still available daily.
analysis • Document Engage with all staff to ensure they are aware of
the policy and know where to find it in ward and
• Compare to problems theatre – test methods of communication e.g.
predictions • Begin data email, face-to-face, phone call, clinical meetings.
• Summarize analysis Stock of antibiotics checked by theatre staff
daily/weekly or topped up by Pharmacy staff
daily/weekly.
Audit antibiotic prescription and administration
documentation in patient medication chart/
When using a quality improvement approach such as the Model notes.
for Improvement it is important to identify data to demonstrate

In the above example the suggested measures are all process Now watch this short video which may help to understand
measures but a potential longer term outcome measure would the importance of clinical engagement and making quality
be surgical site infection rate for patients undergoing vascular improvement everyone’s business:
surgery – review data before and after the intervention.
To ensure that your improvement will be successful test each

change with one member of staff initially then expand to several INTERVIEW WITH DR
staff ensuring each change is tested in all staff groups and in all
theatres.
BRIAN ROBSON (CLINICAL
This is the tried and tested method for implementing sustainable
DIRECTOR OF HEALTHCARE
change but it is important to remember that some tests will fail IMPROVEMENT SCOTLAND AND
and not have the desired outcome. However, this is still useful IHI FELLOW) DISCUSSING WHY
learning and helps to think of new tests to improve practice.
Failed tests may also give us useful information about potential
MEASUREMENT IS IMPORTANT
‘balancing measures’ to help assess unintended outcomes of TO IMPROVE SAFETY IN HEALTH
changes in practice. This will be discussed further in the next
CARE AND WHY EVERYONE
section.
NEEDS TO GET INVOLVED
Improvement, like science, is about learning what works so there
are no ‘bad results’. Some of the greatest scientific achievements
were preceded by failure! WATCH VIDEO
Breakthrough series collaborative
It can be helpful to collaborate with other clinical teams working

on improvement within the same area of practice to share
learning, ideas and what has been successful. This can be done
formally as a breakthrough series collaborative
VIEW COLLABORATIVE
HEALTH-CARE ARTICLE
and there is evidence supporting this approach to achieve

changes in a variety of areas .
"Light bulb" flickr photo by NikonFilm35 https://flickr.com/photos/
nikonfilm35/4209619566 shared under a Creative Commons
(BY-ND) license
VISIT NCBI SITE

“I did not fail one thousand times;
I found one thousand ways how By working in this way it is possible to achieve greater gains
and achieve greater clinical engagement through identifying a
not to make a light bulb.” common area for improvement and working together to optimise
- Thomas Eddison outcomes.

Use of Indicators to be measures across time, between locations and before/

after interventions. There are three main types of indicators –
structural, process and outcome.
STRUCTURAL INDICATORS
Outcome indicators should also include some balancing
measures which reflect how a change in practice may impact
MEASURE WHETHER GOVERNANCE on other parts of the system. A good example of a balancing
STRUCTURES ARE IN PLACE FOR measure is illustrated in a study where a change of policy for
STEWARDSHIP SUCH AS: DOES A surgical prophylaxis in orthopaedic patients to a gentamicin-
HOSPITAL HAVE AN ANTIMICROBIAL based regimen resulted in an increase in acute kidney injury.
TEAM WHICH MEETS REGULARLY,

REPORTS TO SENIOR MANAGEMENT
AND HAS AN ACTION PLAN VIEW JOURNAL ARTICLE
Suitable indicators for stewardship along with some examples

PROCESS INDICATORS from hospitals across the UK are included within the Public
Heath England Start Smart Then Focus publication already
discussed in chapter 10.
MEASURE SYSTEMS IN PLACE FOR
STEWARDSHIP SUCH AS A
SURVEILLANCE PROGRAMME FOR VIEW START SMART THEN
ANTIBIOTIC USE, A PROGRAMME FOCUS PUBLICATION
OF AUDITS, EDUCATION FOR
HEALTHCARE STAFF
Another example of simple measures collected from a small
sample of patients each week is the 5 x 5 audit developed in
Australia. As well as collecting data about prescriptions it also
encourages dialogue with clinical teams to influence prescribing
OUTCOME INDICATORS behaviour.
MEASURE THE IMPACT OF A

STEWARDSHIP PROGRAMME AND
VIEW ANTIMICROBIAL
SHOULD INCLUDE BOTH AUDIT ARTICLE
INTENDED AND UNINTENDED
OUTCOMES SUCH AS REDUCED Sharing data to improve practice
USE OF RESTRICTED ANTIBIOTICS For all types of audit and quality improvement initiatives, regular
(INTENDED) AND INCREASE IN and timely feedback is essential to drive improvements in
RESISTANCE TO RECOMMENDED practice. Sharing prescribing data in real time with front line
ANTIBIOTICS (UNINTENDED). clinicians is the most effective way to allow them to reflect on
their practice and encourage them to change their prescribing
behaviours. Comparison with peers and identification of
prescribers who are outliers are useful techniques to change
Quality Indicators
behaviour.
We can use measures called Quality Indicators on an ongoing
Ideally clinical teams (medical, pharmacy and nursing staff)
basis to monitor quality improvement in both governance of
should collect audit data within their ward or department to give
and use of medicines. Antimicrobial prescribing indicators are
ownership. This is also important because they are the ones that
explicitly defined measureable items of antibiotic use giving a
understand the system most so are best placed to suggest how
possible indication on the level of quality. They can allow trends
improvements could be made.

SPSP Acute Adult End of Phase Report August 2016

http://www.scottishpatientsafetyprogramme.scot.nhs.uk/programmes/acute-adult
Many methods can be used for feeding back data depending Benchmarking
on the audience and whether the data is being used for
Comparing your own data with that of other clinical teams is
scrutiny e.g. targets or for quality improvement. Published
a good way to drive improvement as clinicians can often be
reports, run charts and benchmarking tables are examples of
motivated to make changes if their peers are shown to be
feedback outputs.
performing better than they are.
Run charts The Fingertips AMR portal developed by Public Health England
These simple charts plotting performance against a target over is a good example of how benchmarking has been used to
time are a good way to present improvement data in a visual way compare practice across hospital and community services.
that is easily understood by both healthcare staff and patients/
visitors. These charts have been widely used within many
improvement initiatives to share data and are often displayed on VIEW AMR LOCAL
the wall within a ward/unit. INDICATORS ARTICLE
An example of a run chart which focused on one element of the
Sepsis 6 work, timely administration of antibiotics, in a region of
Fingertips demonstrates how modern IT packages can be
Scotland is shown on the next page:
used to create infographics as an engaging method of
Run charts can be used to set Upper and Lower Control limits as displaying healthcare data that is meaningful to both staff,
in the one above (UCL and LCL) which indicate that something patients and the public.
unusual is happening and alert staff to investigate. They can also
be annotated with text to indicate improvement initiatives such
as training, new documentation or reasons why performance
may be poor e.g. extreme staff shortage.

Planning tools for action and evaluation Driver diagrams
A variety of tools are available to map out what antimicrobial Driver diagrams are commonly used within QI programmes
stewardship programmes and individual interventions are to provide an overall aim then document how this will be
trying to achieve. The reason for using such tools is to ensure achieved through primary drivers, secondary drivers and actions.
that you are clear about your objectives and on how you will An example of a driver diagram for antimicrobial stewardship is
measure progress. shown below:
A summary of the key aims of the national stewardship programme in Scotland are shown in the following Antimicrobial stewardship driver diagram:
AIM PRIMARY DRIVERS PRIMARY DRIVERS

• Identify and reassure patients who do not require antibiotics
Timely and appropriate • Promptly identify patients who require antibiotics and in patients with sepsis syndrome start treatment
antibiotic use in all health within one hour
Timely and appropriate • Obtain cultures (where appropriate) prior to starting antibiotics
and care settings
initiation of antimicrobial • Do not give antibiotics with overlapping activity or combinations not supported by evidence or guidelines
treatment • Determine and verify antibiotic allergies and tailor therapy accordingly
• Improved clinical • Consider local antibiotic susceptibility patterns in selecting therapy
outcomes for patients • Start treatment promptly following local guidelines
with infections • Specify expected duration of therapy based on evidence and national and local guidelines
• Decreased incidence • Clearly identify currently prescribed antibiotics, indication for treatment, start dates and intended duration or
review date for each patient at the point of care
of antimicrobial-related
Appropriate • Give antibiotics at the right dose and interval
adverse drug events • Stop or de-escalate therapy promptly based on the culture and sensitivity results; consider role of biomarkers
(ADEs) administration and
• Ensure therapeutic drug monitoring and dosage adjustment is carried out reliably
de-escalation • Reconcile and adjust antibiotics at all transitions and changes in patient’s condition
• Decreased prevalence • Consider need for use of IV route throughout the patient's episode of treatment; consider IVOST
of antimicrobial resistant • Monitor for toxicity reliably and adjust agent and/or dose promptly when required
healthcare-associated
• Establish stewardship as an organisational priority, ensure resources are made available and indentify
pathogens
accountability
Stewardship infrastructure, • Ensure local structures for antimicrobial stewardship and links to management, infection prevention and
• Decreased incidence control and patient safety are in place
of healthcare-associated data monitoring and staff
• Monitor, feedback, and make visible data regarding antibiotic utilization, antibiotic resistance, ADEs, CDI,
Clostridium difficile education cost, and adherence to the organization’s recommended culturing and prescribing practices
• Ensure national and local education programmes on antimicrobial stewardship meet the training needs of
infection (CDI)
health and care staff and promote patient and public awareness about use of antimicrobials
• Improved cost-effective
Availability of expertise • Develop and make available multi-professional expertise in antimicrobial use
use of antimicrobials
at the point of care • Ensure expertise is available at the point of care across all health and care settings
Based on the CDC/IHI Antimicrobial stewardship Driver Diagram

https://www.cdc.gov/getsmart/healthcare/pdfs/Antibiotic_Stewardship_Driver_Diagram_10_30_12.pdf
Double diamond model
The Double Diamond model is another approach to plan QI

initiatives which is based on behavioural science. This model
is useful for small scale changes within a single ward or
department and is informed by considering 4 key phases. A
key feature of this model is the need for engagement of staff
throughout.

This article from the Design Council explains more about

Direct control
this model:
Input Outputs and activities
VIEW DESIGN Resources – funding, ideas, Antimicrobial prescribing

Antimicrobial Team staff time guidance document in
COUNCIL ARTICLE various formats
Direct influence
Planning how you will undertake QI is important before getting
Short term outcomes
started with data collection but it is also important to think about
how to evaluate impact and this is best done at the start. There Reach and reaction Capacity and capability
are various models which can be used to do this and these
Clinicians access the Increased knowledge
focus on short, medium and long term outcomes of your overall
guidance and skills in prescribing
stewardship programme and/or a specific QI initiative.
Clinicians report they find the antimicrobials
The logic model is a tool that can be used to monitor and guidance useful Change in behaviour in
evaluate short-, medium- and long-term outcomes that are linked prescribing antimicrobials
to the key activities of a programme of work. They are commonly
used to evaluation public health interventions and useful further
information is available including templates.
Indirect influence
Medium and long term outcomes
Decisions and practice Patient and service

VIEW LOGIC MODELS
Individual clinicians report Improved patient safety
improved behaviour in Increased compliance
antimicrobial prescribing in with guidance and optimal
The outcome evaluation framework, sometimes also called
line with guidance outcomes for patients with
‘Contribution analysis’, is a similar model and seeks to detail
activities, outputs and outcomes together with measures Spread of effective infections
of impact at various points in time. This type of approach prescribing across team(s)
acknowledges the complexities of healthcare and does not
assume that outcomes are solely due to the interventions
described but that the interventions contribute to the eventual
outcome which is trying to be achieved. The tables opposite
illustrates how this framework may be applied to development
and implementation of antimicrobial guidance.
HOW TO GET STARTED WITH IMPROVING

Hopefully this chapter has provided information and practical
advice about how to get started with some small scale data
collection to inform some local improvement work. To conclude
here is a summary of what to consider in your own setting.

CHAPTER 12
AUTHORS: ESMITA CHARANI & PETER DAVEY
ANTIMICROBIAL
STEWARDSHIP AND
BEHAVIOUR CHANGE
LEARNING OUTCOMES
CHAPTER IS TO:
• How culture and context determine antibiotic prescribing behaviours
This chapter aims to describe • Why the influence of culture on antibiotic prescribing behaviours need to be investigated
the cultural and contextual and included in initiatives to optimise antibiotic use in secondary care.
determinants of antibiotic
• the key components of quality improvement in healthcare and how this links to
prescribing behaviours in
behaviour change science
secondary care.
THE NEED TO OPTIMISE ANTIBIOTIC PRESCRIBING

With the continued widespread use of antibiotics, despite alarming increase in the
development and spread of resistant pathogens, organisations have focused their
efforts on getting the bug-drug-patient combination right to ensure their effectiveness (1).
Interventions to optimise antibiotic use in hospitals range from the restrictive to persuasive
and include use of technologies such as electronic prescribing systems, smartphone apps
and clinical decision support systems. In the last decade there has been increased efforts
to address the rise of antibiotic resistance on a global scale with the WHO and national
governmental organisations contributing to the debate.
Antibiotic therapy remains an area of medicine that requires knowledge and expertise,
however due to the ubiquitous nature of infectious diseases and healthcare acquired
infections, all healthcare professionals will treat patients with an infection. Worldwide,
diagnosis and treatment of infections is being undertaken by healthcare professionals in
all specialties and yet it is estimated that up to one third of hospital antibiotic prescriptions
are inappropriate. Trying to explain the concept of collateral damage caused by
inappropriate antibiotic use to healthcare professionals remains a challenge.
Clearly optimisation of antibiotic prescribing requires healthcare professionals (HCPs)

to change their practices. Therefore, antibiotic interventions are all concerned with
behaviour change.
Culture plays a role in this subject, but to date has been largely neglected and left out of
the equation with most research in antibiotic stewardship, focused on the easily tangible
and measurable for example producing policy and guidelines, measuring resistance, and
measuring prescribing, with some education and training mainly for junior doctors. As one

CHAPTER 12 - ANTIMICROBIAL STEWARDSHIP AND BEHAVIOUR CHANGE
of the core goals of antimicrobial stewardship is to improve

patient safety a report on the importance of a patient safety
culture is very pertinent. TOOLKIT RESOURCE
A recent Cochrane review found that interventions were VIDEOS
more effective if they were designed to enable prescribers Talk by Professor Mary Dixon Woods on what we
by increasing their capability or opportunity to follow policies. know and what we need to improve about quality and
This finding applied to restrictive interventions as well as safety in hospitals
to educational or persuasive interventions. However, few
interventions used the most effective enablement techniques of WATCH VIDEO
goal setting and feedback combined with action planning.
Lecture on Social determinants of Health
VISIT SITE WATCH VIDEO
DOWNLOAD SLIDE SET

THE ROLE OF BEHAVIOUR AND CULTURE E Charani MOOC slides
IN ANTIBIOTIC PRESCRIBING
There is increasing qualitative evidence, indicating antibiotic
SITE LINK
prescribing to be more complex than a simple case of following Importance culture patient safety
guidelines (3). In the field of antibiotic stewardship, evidence
points to the influence of culture as a key determinant of
antibiotic prescribing behaviours.
healthcare professionals rarely refer to explicit guidelines, rather,
Culture can be defined in many ways. We use the definition
they used collectively reinforced internalised tacit mindlines that
of culture by Spradley:
were structured from personal and colleagues’ experiences,
Culture, he defines, is the acquired knowledge people use to and interactions with opinion leaders. HCPs they found, used
interpret, experience and generate behaviour. socially constructed knowledge. In secondary care, culture
can be a key determinant of behaviours. Mary Dixon Woods
It refers to how people learn and moderate their behaviours
and colleagues conducted an ethnographic study across 200
as members of a team. Culture does not have to underpin
intensive care units in England. These units had implemented
everything we do. But we use it as a cognitive map, a GPS to
the Matching Michigan programme to reduce central line
navigate our behaviours with.
infections. The common trait of successful units was that they
But why is culture important in this field? As mentioned before had made efforts to develop an understanding of the context in
if all antibiotic stewardship programmes have behaviour change which the interventions were being implemented. As a result,
as an outcome, and in view the definition of culture by Spradley, any hierarchies were removed and local leaders were involved
then all antibiotic stewardship programmes are concerned in the decision-making process. Unsuccessful units, had not
with the culture within healthcare. We avoid culture at our peril. engaged with senior consultants as part of the implementation
It has been said that “culture eats strategy for breakfast”. So, process of the programme. This study reinforced the need
we want to use some evidence from literature to see if this account for local cultures and context in the development and
saying holds true. implementation process of clinical interventions that aim to
change behaviours of healthcare staff. Engaging with clinical
In a study in three primary care GP surgeries over two
leaders and recognising local champions acknowledges the
years, Gabbay and colleagues used ethnography methods
hierarchies which dominate healthcare.
to investigate how GPs access evidence based guidelines.
Ethnography is a study of people in the context of their social
and physical environment, and includes observations, face to
face interviews and documentary analysis. What they found, and VIEW IMPROVEMENT
defined as mindlines, was really culture at work (2). In their two PROGRAMMES DOCUMENT
years of observing doctors and nurses they discovered that

Culture has also been studied across different specialties of HIERARCHIES

medicine and surgery in order to describe the observed variation
Medical practice is historically hierarchical where knowledge,
in antibiotic prescribing behaviours.
experience and expertise are highly prized. Tribalism in medicine
Ethnography has also been used to describe the influence has been described and discussed in the literature. Further
of culture and team dynamics on the antibiotic prescribing evidence of the conflict between the behaviours of individuals,
behaviours of surgical teams in a study conducted across 6 the medical hierarchy and guidelines and policy can be found
surgical teams in a large teaching hospital in London. The in a qualitative study where 39 healthcare professionals
surgeons in this study were inclined to see themselves as from nursing, medical and pharmacy professions across
‘interventionist’ whose primary responsibility is the surgical three hospitals in a large teaching NHS Trust in London were
intervention. In this context, antibiotic decision making was interviewed. The study explored their perceived self-reported
commonly delegated to others. This study provided a determinants on antibiotic prescribing. What was identified was
platform for an international research collaboration investigating the existence of tacit rules governing prescribing. Hierarchy
antibiotic prescribing in the surgical pathway in low and middle and prescribing etiquette overruled policy and guidelines:
income countries. Senior clinicians wielded significant influence on the prescribing
choices and decisions of junior doctors.
In another study conducted at Imperial amongst the medical

TOOLKIT RESOURCE specialty, doctors perceived that the de-escalation and
stopping of antibiotics was the responsibility of senior doctors.
SITE LINKS The junior doctors also reported a lack of feedback on their
Charani E, Castro-Sanchez E, Sevdalis N, et al. prescribing decisions. The study called for a need to improve the
Understanding the determinants of antibiotic communication and feedback to junior prescribers in order to
prescribing within hospitals: The role of help them develop optimised antibiotic prescribing behaviours.
“prescribing etiquette.” Clin Infect Dis. Is the impact of hierarchy the same everywhere? When the
2013;57(2):188-196. qualitative study design conducted at Imperial (Charani et al CID
2013) was replicated in Norway it was interesting to find differing
Graphic results with hierarchy not emerging as a key determinant. This
may be because Norway, being a more egalitarian society with
Audio file efforts made to flatten visible hierarchies (eg. all hospital staff
wearing the same white uniform), have inadvertently overcome
PDF ARTICLE some barriers which still exist in many other healthcare
organisations globally.
A literature review of behavioural analysis of
behavior change and antimicrobial prescribing In Norway, geographical access to laboratories was a more
in healthcare settings pressing barrier to effective antibiotic prescribing and
stewardship:
SITE LINK
NCDI
VIEW ARTICLE
Should surgeons be allowed to prescribe
NCDI Internationally however, the influence of culture and senior

colleague influence on decision making remain powerful
determinants of antibiotic decision making. In a survey of the
week five participants of the MOOC course the 505 respondents
(from 53 countries) overwhelmingly ranked the opinion of senior
colleagues above the recommendations in policy and guidelines
in relation to antibiotic decision making (ECCMID 2017 abstracts).

h There are specific actions that have been proven to lead to

successful behaviour change across an array of topics:
VISIT ESCMID SITE Goal setting and Action Planning
Goal setting includes agreeing on a defined “how good by when”

goal in terms of the behaviour to be achieved. Action planning
BEHAVIOUR CHANGE AS QUALITY involves prompt planning of performance of the behaviour.
IMPROVEMENT Goal setting and Action Planning are widely used behavior
Clearly there is evidence that there is a need to employ change techniques, particularly for motivating individuals to
methods from outside the fields of microbiology and drug change behaviours directly impacting themselves such as
discovery, and hospital policy to implement effective antibiotic smoking cessation, and for people with chronic conditions.
stewardship programmes. Though effective to and essential to bringing about behavior
change there is less evidence of their use in antibiotic
Quality improvement interventions take many forms. As we
stewardship interventions.
have seen in the earlier chapters understanding through
measurement, what is happening in your location is key to Audit and Feedback
change and improvement. In its widest sense quality Audit and feedback, which has been tried in stewardship
improvement is the combined and unceasing efforts of everyone interventions, is the monitoring and feedback provision on
to make changes that will lead to better patient outcomes, better outcomes of behaviour to the people whose behaviour is
system performance (care) and better professional development. expected to change. A summary of all the behaviour change
techniques that are applicable to antibiotic stewardship are in
Change making should become an intrinsic part of everyone’s
the references below:
job, every day, in all parts of the system.
Changing systems is only part of the improvement arsenal –

behaviours also need to be improved. In relation to antibiotic
prescribing what behaviours need to change and how?
VISIT SCIENCE DIRECT SITE
Despite existing policies and guidelines, antibiotic use in
hospitals continues to be suboptimal, in the face of rising
resistance. Evidence from social sciences can help develop more
sustanble and context driven stewardship interventions. To help
develop more contextually driven interventions we can learn
VISIT NICE SITE
from existing behavior change techniques employed in other
fields.
There is an emerging body of evidence supporting the right
Some behaviour change techniques (BCTs): methods for applying behavior change techniques such as
COM-B Model (Capability, Opportunity, Motivation – Behaviour) audit and feedback. A Cochrane review on audit and feedback
and its effect on healthcare professional behaviours has been
This technique is based on the premise that for any change in
published. In it the authors identify the key steps to successful
behavior, a person must:
and effective audit and feedback as:
• Be physically and psychologically capable of performing the 1) utilising multimodal approach to delivery of the feedback
necessary actions (e.g. textual and graphic);
• Have physical and social opportunity to change their 2) providing more than once (i.e. up to monthly, repeated
behaviour feedback);
• Have more motivation to adopt the new behaviour, rather 3) being delivered by a trusted colleague or supervisor;
than the old behaviour.
4) targeting behaviours where there is significant room for
improvement (i.e. baseline performance is low); and
VISIT BEHAVIOUR 5) being accompanied by explicit recommendations for

CHANGE SITE changing practice (i.e. goals and action plans)

The British Society for Antimicrobial Chemotherapy (BSAC) has References and additional materials
led the Cochrane systematic review of interventions to improve 1. Davey P, Marwick CA, Scott C, Charani E, McNeil K, Brown E,
antibiotic prescribing to hospital inpatients. Working with et al. Interventions to improve antibiotic prescribing practices for
Professor Susan Michie, Director of the Centre for Behaviour hospital inpatients. Cochrane Database Syst Rev 2017. 2017;(2).
Change at University College London, data extraction sheets
2. Gabbay J, LeMay A. Practice-Based Evidence for Healthcare:
were designed that identifed BCTs in the 214 papers in the
Clinical Mindlines. In: PRACTICE-BASED EVIDENCE FOR
review. In this power point slide Prof Peter Davey leads you
HEALTHCARE: CLINICAL MINDLINES. 2011. p. 1–269.
through the review process and highlights the key points.
3. Charani E, Edwards R, Sevdalis N, Alexandrou B, Sibley
E, Mullett D, et al. Behavior change strategies to influence
antimicrobial prescribing in acute care: A systematic review. Vol.
TOOLKIT RESOURCE 53, Clinical Infectious Diseases. 2011. p. 651–62.
SLIDESET
Reading resources:
Behaviours and BCTs - Peter Davey
1. Skodvin B, Aase K, Charani E, Holmes A and Smith I. An
antibioticstewardship program initiative: A qualitative study on
prescribing practices among hospital doctors. ARIC under review.
http://www.ncbi.nlm.nih.gov/pubmed/26075065
EXAMPLES OF SUCCESSFUL APPLICATION 2. Davey P, Peden C, Charani E, Marwick C, Michie S. Time
OF BEHAVIOUR CHANGE THEORY TO for Action: Improving Design and Reporting of Behaviour
ANTIMICROBIAL STEWARDSHIP RESEARCH Change Interventions for AntibioticStewardship in Hospitals;
Despite the emerging evidence indicating the strong influence Early Findings from a Systematic Review International
of culture and team dynamics, it is disappointing to see so Journal of AntibioticAgents. 2015 Mar;45(3):203-212. doi:
few new papers emerging which attempt to incorporate better 10.1016/j.ijantimicag.2014.11.014. http://www.ncbi.nlm.nih.gov/
social science into antibiotic stewardship programmes as it pubmed/25630430
has an important role to play to improve the implementation of 3. Gabbay J, May A. Evidence based guidelines or collectively
antimicrobial stewardship. We can learn from existing examples constructed “mindlines?”. Ethnographic study of knowledge
of interventions where social science and behavior change management in primary care. BMJ. 2004;329:1013. doi:10.1136/
science can be applied to produce more effective outcomes. bmj.329.7473.1013.
There are several examples of using behavior change and social http://www.ncbi.nlm.nih.gov/pubmed/15514347
science research to inform antibiotic prescribing interventions.
4. Dixon-Woods M, Leslie M, Tarrant C, Bion J. Explaining
These are summarised in two recent invited reviews in JAC:
Matching Michigan: an ethnographic study of a patient safety
1. Toma M, Davey P, Marwick C, Guthrie B. A framework for program. Implement Sci. 2013;8(1):70. doi:10.1186/1748-5908-8-70.
ensuring a balanced accounting of the impact of antimicrobial http://www.ncbi.nlm.nih.gov/pubmed/23786847
stewardship interventions. J Antimicrob Chemother
5. Rawson TMM, Charani E, Moore LSPS, et al. Mapping the
2017;72(12):3223-31
decision pathways of acute infection management in secondary
2. Driving sustainable change in antimicrobial prescribing care among UK medical physicians: A qualitative study. BMC
practice – How can social and behavioural sciences help? Med. 2016;14(1):208. doi:10.1186/s12916-016-0751-y.
Fabiana Lorencatto,Esmita Charani,, Nick Sevdalis, Carolyn
6. Charani E, Tarrant C, Moorthy K, Sevdalis N, Brennan
Tarrant & Peter Davey. JAC 2018 in press (hopefully!)
L, Holmes AHH. Understanding antibiotic decision making
As the evidence in this chapter has demonstrated social science in surgery – a qualitative analysis. Clin. Microbiol. Infect.
research can address a key gap in antibiotic stewardship 2017;23(10):752-760. doi:http://dx.doi.org/10.1016/j.cmi.2017.03.013.
programmes by helping healthcare professionals develop
contextually driven interventions that are sustainable.

CHAPTER 13
AUTHOR: DIANE ASHIRU-OREDOPE
KNOWLEDGE AND
PRACTICE IN STEWARDSHIP:
EDUCATIONAL
COMPETENCIES FOR
PRUDENT PRESCRIBING
LEARNING OUTCOMES
CHAPTER IS TO:
• Understand the current landscape of educational competencies globally
highlight the current • Describe the educational strategies available for AS
landscape and development
• Describe the process for developing competencies
of educational competences
for prudent prescribing. • List published competencies for prudent prescribing
• Consider which educational resources could be useful in their location
INTRODUCTION
Increasing knowledge and improving prescribing practice through education is considered
an important and core persuasive AMS intervention, in comparison to restrictive
interventions such as formulary restrictions.
Educational strategies can be either passive or active. Examples of passive and active
education strategies include:
• Pprinted antimicrobial prescribing guidelines, prescribing guidelines on

organisation’s website, posters, handouts, conference attendance, staff/teaching
sessions with minimal interactive sessions (passive strategies)
• Focus groups for consensus-building, workshops, one-on-one targeted sessions

e.g. via academic detailing or educational outreach by clinical educators (eg ID
physician/microbiologist or pharmacist) (active strategies)
Whilst increasing knowledge is an essential step in improving antimicrobial stewardship,

education alone has been shown to be only marginally effective in changing prescribing
practices and has not been shown to have a sustained effect.
Face-to-face educational visits have been shown to have greater and longer lasting effects
on changing prescribing behaviour than printed material or group interactions alone.1

CHAPTER 13 - KNOWLEDGE AND PRACTICE IN STEWARDSHIP: EDUCATIONAL COMPETENCIES FOR PRUDENT PRESCRIBING
The technique has been cited the most likely effective single
method for changing prescribing behaviour. However it is
resource intensive.
WHY IS ANTIBIOTIC RESISTANCE
In this chapter, the current landscape of knowledge and practice
EDUCATION SO IMPORTANT
is highlighted as well developing educational competencies for FOR HCPS AND THE PUBLIC?
prudent prescribing.
In the context of this chapter, all healthcare professionals and WATCH VIDEO
health students are considered, including doctors, pharmacists,
nurses, dentists and other allied healthcare professionals.
In many countries only doctors and dentists can prescribe Responses to this call for AMR as a core component of education
antimicrobials, but increasingly, nurses and pharmacists can is the development of educational resources such Massive Open
independently prescribe medicines including antimicrobials. On-line Courses with global reach
Other allied healthcare professionals such as podiatrists and
physiotherapists may also have a key role in influencing referrals
CURRENT LANDSCAPE: NATIONAL
of patients with infections which require antimicrobials.
STRATEGIES TO IMPROVE AMS
The importance of improving awareness, understanding of KNOWLEDGE AND PRACTICE
antimicrobial resistance through effective communication,
There are a number of steps that governments, educational
education and training is indeed the first objective of the WHO
establishments, professional bodies have taken to implement
Global Action Plan on Antimicrobial Resistance. In particular, the
objective 1 of the global action plan. The first open survey of
need to make AMR a core component of professional education,
countries' national action plan preparedness on Antimicrobial
training, certification and CPD (Figure 1 ).
Resistance (AMR) at the 70th World Health Assembly highlights
the progress made so far by countries across the world.
147 governments representing 95% of the world’s population

“Steps need to be taken immediately responded (Figure 2 and Table 1.)
in order to raise awareness of
antimicrobial resistance and promote Total %
behavioural change, through public A. No training for health workers on 12 8.2
communication programmes that AMR
target different audiences in human B. Ad hoc training courses in some 44 29.9
health, animal health and agricultural health-related disciplines.
practice as well as consumers. Inclusion C. AMR is covered in some pre- 48 32.7
of the use of antimicrobial agents service training and/or some special
and resistance in school curricula will courses for health workers.
promote better understanding and D. Continuing professional 36 24.5
awareness from an early age.” development (CPD) opportunities
are available nationwide for health
“Making antimicrobial resistance a core workers on AMR and implications
component of professional education, for antimicrobial use & infection
training, certification, continuing prevention.
education and development in the E. AMR is systematically 5 3.4
health and veterinary sectors and incorporated in pre-service training
agricultural practice will help to ensure curricula for all relevant health
proper understanding and awareness cadres. Regular CPD on AMR
among professionals.” reaches relevant groups for human
health nationwide, in public and
WHO Global Action Plan 20152 private sectors.
No response provided 2 1.4
TABLE 1
FIGURE 1 Steps countries have taken on the question Training and professional
WHO Global Action Plan - objective 1 on education and training education on AMR in the human health sector

The survey highlights progress made:
• 77 countries having multi sectoral plans
• 57 in the process of developing one.
• 37 reported having no formal plan.
High income countries generally reported having more capacity

in all aspects of responding to the challenge of tackling AMR,
but significant challenges with low-middle income countries and
especially fragile states.
Tackling AMR in human health systems is progressing better

than animal health, this is perhaps most evident for training
where only 12 countries have no training in the human health
sector compared to 33 countries in the veterinary sector
(Table 1).
The five countries that selected option E were Belarus, Norway,

FIGURE 3
United Kingdom (EURO region), Haiti (AMRO) and Lebanon
Global map of answers on actions on AMR training for healthworkers3
(EMRO). Majority of the countries that have no training for health
workers on AMR are in the African (6), WHO South-East Asia (2),
Western Pacific (4) regions (Figure 1).

TOOLKIT RESOURCE
SITE LINKS
1 Avorn J, Soumerai S. Improving drug-therapy
decisions through educational outreach:
a randomised controlled trial of academically
based ‘detailing’. New England Journal of
Medicine 1983;308:1457–1461
3 WHO 2015. Global action plan on antimicrobial

resistance
4 WHO HQ Reports
ARTICLE
2 Dartnell J. Understanding, Influencing and
Evaluating Drug Use. North Melbourne, Victoria:
FIGURE 2 Therapeutic Guidelines Ltd, 2001
Steps that governments have taken to implement objective 1 of the
global action plan

EXAMPLES OF HOW COUNTRIES HAVE • The most popular formats of resources were training
IMPLEMENTED OBJECTIVE 1 OF THE workshops.
GLOBAL AMR ACTION PLAN • More than 75% of the resources were targeted towards the
Table 2: provides a summary of antibiotic awareness/ education training of medical prescribers (of all grades in both primary
and training strategies as written in national antimicrobial and secondary care including dentists)
resistance action plans. The national survey highlighted the general approaches at a
Below we provide examples of how these have been local/regional level to education and training (Figure 3):
implemented
UK LOCALLY DEVELOPED E-LEARNING FOR

In the UK, the Health and Social Care Act: code of practice on PRESCRIBERS, ADMINISTRATORS AND
the prevention and control of infections and related guidance DISPENSERS OF ANTIMICROBIALS.
(DH 2015)4 states that healthcare providers should ensure
that all prescribers receive induction and training in prudent Locally relevant presentations, quizzes and role-play
antimicrobial use and are familiar with the antimicrobial simulation, workshops, leaflets and in-house learning
resistance and stewardship competencies. materials, classroom lecture as part of non-medical
prescribing (NMP) course, and continual professional
There are also recommendations in national guidance that there development (CPD) session on antimicrobial use e.g. to
should be mandatory core training in prudent antibiotic use for medical meetings / grand rounds.
doctors, pharmacists and nurses, in addition to an introductory
Bulletins, short talks, smartphone and website apps,
session on each induction programme and that this should be
feedback sessions, guidelines and pharmacy team alerts.
repeated every three years, with particular emphasis on those
antibiotics that provoke C. difficile infection (CDI) (PHE & DH Mandatory antimicrobial prescribing training.
20085; PHE 20116).
Teaching underpinned by antibiotic audits and C.Diff data
Finally in 2013, the national action plan on antimicrobial analysis
resistance specified actions required to improve professional
Distance learning through Future Learn (e.g. AMS-MOOC)
education and training and public engagement
and the e-learning (e.g. through TARGET on the RCGP
The first national antimicrobial prescribing and stewardship website
competences to be developed anywhere in the world were Training sessions for everyone involved with medications.
published in 2013 by the United Kingdom. The antimicrobial
prescribing and stewardship competences complement in Newsletters, communications and weekly surveillance
the UK generic competency framework7 for all prescribers
Training resources created after identifying problems via
(2016) which expects prescribers to understand antimicrobial
audits and root cause analysis (RCA)
resistance and the roles of infection prevention and antimicrobial
stewardship. Lecture/seminar delivered by an external specialist
antimicrobial pharmacist and external expert university
Since then the implementation of the competences have been
lecturer
assessed in undergraduate curricular as well as the educational
approaches to improving the knowledge of prescribers One to one teaching in clinical settings with case studies on
antibiotic prescribing, delivered as a workshop format with
• Educational approaches to improve knowledge of
discussions
antimicrobial prescribing
Individual trust-led campaigns
A national survey to identify what learning materials and
resources are currently available to support prescribers Prescribing app
with learning and education around AMR and antimicrobial
prescribing highlighted that Multi-professional sessions
• In 61% of responding organisations, all prescribers receive English surveillance programme for antimicrobial utilisation
induction and training in prudent antimicrobial use. and resistance (ESPAUR) data presentation
• 40% confirmed prescribers are familiar with and/or given

FIGURE 4
the PHE/ARHAI antimicrobial resistance and stewardship
general approaches at a local/regional level to education and training
competencies.

Australia China
Antimicrobial Stewardship in Australian Hospitals 2011 Following a survey in 2016, educators in Chinese medical
In Australia, it is recommended that prescribers are taught to schools have recognised the importance of developing AMR
prescribe according to the Therapeutic Guidelines on Antibiotics education and training programmes. Three AMR education and
at undergraduate, postgraduate and professional development training programmes were designed following a national project:
programmes. Hospitals are highlighted as responsible for (1) a programme for undergraduate students in medical schools
educating clinical staff about local AMS programmes (Figure 4). has been approved and launched at Peking University as an
optional course open to all undergraduate students; (2) a training
programme for chief pharmacists on antimicrobial stewardship
has launched its pilot projects in five provinces across China; (3)
VIEW AMS DOCUMENT the programme for students in clinical medical students have
been approved to be launched at Peking University from 2017.
India
Ghana Strategic priority 1 of India’s AMR action plan 2017 – 2021,
As part of developing its national action on plan on AMR, focuses on improving awareness and understanding of AMR
Ghana conducted baseline assessment of knowledge, attitudes, through effective communication, education and training, and
beliefs and practices of not only healthcare professionals has 2 focus areas – first is communications and information,
but also Civil Society Organisations in health8. Following this education, communication (IEC) resources to raise awareness
a training programme for media practitioners, pharmacists, amongst all stakeholders, and second focus area is education
nurses, traditional rulers and civil society organisations/non and training to improve the knowledge and behaviour of
governmental organisations was implemented from 20159 professionals in all sectors.
VIEW AMR DOCUMENT
South Africa
In South Africa as part of implementing the national AMR action
plan, an antibiotic prescribing license to be awarded following an
antibiotic prescribing course is being developed in collaboration
with the Health Professions Council of South Africa and
providers of health. It was envisaged that it would be a biennial,
renewable, web-based qualification.
In addition,
• there are two national training centres which rapidly train
prescriber-pharmacist-hospital manager teams from provincial
hospitals throughout SA to promote the initiation of ASPs in
their hospitals and in turn train local practitioners in
stewardship
From a presentation given by Director of Pharmaceutical Services
Ministry of Health Ghana - Martha Gyansa and
• An open learning free course on Clinical Antibiotic
Stewardship for which a certificate of completion is awarded
for practitioners who complete the course,
VIEW CLINICAL ANTIBIOTIC

STEWARDSHIP ARTICLE

FREE WORLDWIDE ACCESS

TO AMS TRAINING
CLINICAL ANTIBIOTIC
Free worldwide access to AMS training is available through
STEWARDSHIP FOR Massive Open Online content (MOOCs) are available from the
SOUTH AFRICA universities of Uppsala (Sweden)10 and Dundee (UK)11.
WATCH VIDEO
FIGURE 5
Antimicrobial Stewardship: Managing Antibiotic Resistance FIGURE 6
by University of Dundee and British Society for Antimicrobial Antibiotic Resistance: the silent Tsunami by Uppsala University
Chemotherapy Sweden

ACTIONS RELATING TO GLOBAL ACTION PLAN STRATEGIES TO IMPROVE ANTIBIOTIC PRESCRIBING/

COUNTRY
OBJECTIVE 1 STEWARDSHIP PRACTICES
• A National AMS network to co-ordinate national

projects aimed at producing a consistent approach
• Develop public campaigns across sectors to increase to AMS.
Australia antibiotic resistance awareness through education • Develop resources to support the implementation
and training. of AMS. Existing accreditation and quality assurance
programmes to be reviewed to ensure compliance
with AMS practices.
• Increase promotion of appropriate use of
• Support research and dissemination of results
Canada antimicrobials in human and animal medicine using
regarding research on stewardship measures.
AMR awareness campaigns.
• Creating a checklist approach for developing
• Increasing education and awareness of AMR aimed
communication strategies for doctor/patient
at the public.
discussions regarding the use of antibiotics.
Germany • Developing a training programme for continuing
• Developing an online forum for healthcare
professional development (CPD) and determining
professionals.
whether CPD in AMR could be enforced.
• Certain hospitals to contribute towards quality reports.
• Develop the Prescription Register to incorporate a
• Improve the level of understanding of AMR amongst
diagnostic code on all antibiotic prescriptions for
the general population by implementing mass media
humans to allow antibiotic use to be recorded.
Norway campaigns.
• Review the possibility of setting up a feedback system
• Set up infection control conferences for healthcare
for GP prescribing and offer peer review assessments
personnel which focus on antibiotic guidelines.
of antibiotic prescribing.
• Developing a national awareness campaign aimed at
all healthcare workers and public and a strategic plan
• The self-evaluation of prescribers will be developed
Spain for education and training.
and encouraged.
• An ongoing training programme will be set up for
healthcare professionals regarding AMR.
• Provide leadership and guidance to develop effective
AMS at all levels.
• AMR public awareness campaigns to be introduced, • Incorporate AMS activities into job descriptions,
South Africa including vaccination awareness. performance appraisals and CPD activities.
• Core curricula for AMR will be implemented. • A series of AMS interventions are being implemented
(for example, AMS ward rounds and a dedicated
antibiotic section in drug charts).
• Embed infection prevention practices into all education
programmes for healthcare workers.
• Ensure adherence to local guidelines. • Work with Royal Colleges and professional bodies to
UK • Audit local prescribing to determine the outcome of identify how to use appraisal and revalidation systems
antimicrobial stewardship practices. to reinforce AMS.
• Increase public engagement focusing on the
appropriate use of antimicrobials.
• Support other countries to develop and implement
• Implement public health programmes. By 2020, set
national plans and strategies to enhance AMS.
USA up antimicrobial stewardship programmes in all
• Develop appropriate metrics to determine the success
acute hospitals.
of AMS effort.
TABLE 2
A summary of antibiotic awareness/ education and training strategies in national antimicrobial resistance action plans 1 2

WHAT ARE COMPETENCES FOR

ANTIMICROBIAL PRESCRIBING AND
TOOLKIT RESOURCE STEWARDSHIP
SITE LINKS Competences, or a competency framework, are sets of
5 https://www.gov.uk/government/publications/the- behaviours that are instrumental in the delivery of desired
health-and-social-care-act-2008-code-of- results.13 14 These behaviours support individuals and an
practice-on-the-prevention-and-control-of- organisation in the attainment of organisational set objectives.
infections-and-related-guidance Why are competencies important?
Competences can be used by prescribers to help develop
6 https://www.gov.uk/government/publications/ their prescribing practice at any point in their professional
clostridium-difficile-infection-how-to-deal-with- development in relation to prescribing antimicrobials and can
the-problem be used to plan continuing professional development in order to
maintain and improve their competence.
7 https://www.gov.uk/government/publications/
In addition to the individual benefits of competences,
antimicrobial-stewardship-start-smart-then-focus
competences can also provide clarity for regulators, education
providers and professional bodies to inform standards, guidance
8 https://www.rpharms.com/resources/frameworks/ and the development of training.
prescribers-competency-framework
To understand the level of competence, it is necessary for
individuals to undertake an honest assessment of their current
9 http://ghndp.org/reactcso/index.php/ghana-
level of knowledge and skills and their ability to apply them
cso-reports/144-report-assessment-of-the-
in practice. The help of others (e.g. colleagues, peers and/
knowledge-attitudes-beliefs-and-practices-of-
or manager) can be sought in this assessment. Once there is
civil-society-organisations-in-health-on-antibiotic-
a realistic assessment of knowledge, skills and competence,
use-and-resistance
learning needs and how these can be met can be determined.
It will be important to revisit the competences and ensure
10 http://ghndp.org/reactcso/index.php
continuous assessment to identify progress in achieving all of
the competences.15 It is important that developed competences
11 https://www.futurelearn.com/courses/antibiotic-
should align with relevant national/international guidance
resistance
and resources
12 https://www.futurelearn.com/courses/
antimicrobial-stewardship
WHO SHOULD THE COMPETENCES BE
INTENDED FOR?
13 Adapted from: Sadak M, Cramp E, Ashiru- Antimicrobial Prescribing and Stewardship competences should
Oredope D. Current Treatment Options in be developed for all healthcare workers but in particular for
Infectious Diseases 8 (2) 57–712 https://www.
Independent prescribers:
futurelearn.com/courses/antimicrobial-
- A primary care/family medicine doctor
stewardship
- Physicians
- Surgeon
- A medicine trainee
- A first year graduate from medical school who can write and
SUMMARY sign antimicrobial prescriptions
Whilst national AMR action plans include education and - A nurse or pharmacist prescriber who can prescribe a range
training, currently the global picture of implementation is mixed, of antimicrobials for a range of clinical conditions, without
highlighting more work and coordination is required. supervision.
- A dentist who can prescribe several different antimicrobials

As well as non-independent prescribers (where relevant) CURRENT LANDSCAPE: DEVELOPED

including: COMPETENCES ACROSS THE WORLD:
- Nurse or pharmacist prescribers who can only prescribe UK - NATIONAL COMPETENCES
specific antimicrobials (e.g. trimethoprim) in specific
circumstances (e.g. urinary tract infections)
- Final year medical students who are encouraged to write DEVELOPMENT OF THE FIRST
prescriptions, but need a qualified doctor to sign the
prescription
NATIONAL ANTIMICROBIAL
STEWARDSHIP COMPETENCES
WATCH VIDEO
TOOLKIT RESOURCE
ARTICLES
14 Whiddett S, Hollyforde S. The Competencies The UK antimicrobial prescribing and stewardship competences
Handbook. London: Institute of Personnel and consists of five dimensions, each of which includes statements
Development, 1999. that describe the activity and outcomes that prescribers should
be able to demonstrate
15 Bartram D, Roberton I, Callinan M. Introduction:
• Educating the public and clinicians in the prudent use
a framework for examining organisational
of antimicrobials as part of an antimicrobial stewardship
effectiveness. In: Robertson IT, Callinan M,
programme is of paramount importance to control AMR.
Bartram D, eds. Organisational Effectiveness:
Improving surveillance, and infection prevention and control
The Role of Psychology. Chichester: Wiley,
are other key strategies.
2002; 1–12.
• Using current available evidence, regulatory documents
and national antimicrobial stewardship guidance for
primary and secondary care, five competency dimensions
DEVELOPING COMPETENCES (31 statements) for antimicrobial prescribing and stewardship
Competences should be developed using an evidence-based competences were developed in England (table 1).
approach. One example of a step-wise approach taken to • The competences are designed to complement the United
develop competences is: Kingdom’s Generic prescribing competency framework for
all prescribers
Defining the target group/audience • The five dimensions of competencies are shown in the table
with one example of a competency statement for each
category
Review of the literature • All competencies can be found on the UK Department of
Health’s website
Review of existing competences and published

curricula/training objectives VISIT DEPARTMENT
OF HEALTH SITE
Synthesis of new competences
Expert panel review and competency refinement using

eg Delphi methodology/expert consensus/workshop

Five Dimensions No of Statements Illustrative example of competency statements

1) Infection prevention and control: all independent 5 statements Understand how current vaccines can benefit
prescribers must understand the principles prescribing practices, including reducing the need for
and demonstrate competence in preventing and prescribing antimicrobials and decreasing resistant
controlling infections antimicrobial resistant strains e.g. of S. pneumoniae.
2) Antimicrobial resistance and antimicrobials: 6 statements Knowledgeable in the appropriate use of antimicrobial
including modes of action and spectrum of agents for:
activities of antimicrobials and the mechanisms • prophylaxis to
of resistance minimise the
risk of infection
• treatment of
infections
3) Prescribing antimicrobials: including the key 8 statements Competent in AM prescribing by demonstrating
elements in prescribing appropriate antimicrobial knowledge of when not to prescribe antimicrobials,
agents for prophylaxis and treatment and use of alternatives, such as the removal of
invasive devices, e.g intravenous or urinary catheters
and incision and drainage of abscesses.
4) Antimicrobial stewardship: demonstrating 8 statements Demonstrate clinical competence and understand
an understanding and including antimicrobial the importance of Appropriately choosing one of the
stewardship in day to day practice five antimicrobial prescribing decisions 48 hours after
initiating antimicrobial treatment (ARHAI Guidance –
Start Smart – then Focus)
5) Monitoring and learning: all independent 4 statements Demonstrate CPD in AMS by using locally agreed
prescribes must demonstrate continuing process measures of quality (eg compliance with
professional development in antimicrobial guidance), outcome and balancing measures, such as
prescribing and stewardship unintended adverse events or complications.
EXPERT PROFESSIONAL CURRICULUM 1. Infection and antimicrobial stewardship in context: awareness

FOR ANTIMICROBIAL PHARMACISTS IN and interpretation of local and national antimicrobial usage
THE UK and resistance data, national and international policy
pertaining to antimicrobial stewardship and global issues
Additionally in the UK, expert professional curriculum has
in AMR.
been developed for antimicrobial pharmacists who mainly lead
antimicrobial stewardship activities in hospitals. 2. Clinical microbiology: theory, laboratory tests and their
interpretation, clinical principles of infection and principles
The curriculum was developed by the UK Clinical Pharmacy
of AMR.
Association Pharmacy Infection Network and endorsed
by the Royal Pharmaceutical Society as a tool to support 3. Antimicrobials: therapeutic drug monitoring, pharmacology,
pharmacists in meeting the requirements for joining the Royal pharmacokinetics and pharmacodynamics, and antimicrobial
Pharmaceutical Society Faculty. The aim of the curriculum was use in special populations.
to support antimicrobial pharmacists in delivery of antimicrobial 4. Management of clinical syndromes: organized by bodily
stewardship. The curriculum is available to view via http://bsac. system.
org.uk/ukcpa-expert-professional-curriculum-for-antimicrobial-
pharmacists/ 5. Principles of an antimicrobial stewardship plan: role of the
stewardship team and key components of hospital and
The curriculum covers five areas and within each area there are primary care stewardship programmes.
three levels of competency that cover professional practice from
being new to the specialty (Advanced stage I), through gaining Examples of the knowledge and behaviours expected at different
experience of complex issues (Advanced stage II) to working at levels are given within the document
national level (Mastery). A Syllabus for Infection and Antimicrobial Stewardship is also
suggested.

GUIDANCE FOR THE KNOWLEDGE AND

SKILLS REQUIRED FOR ANTIMICROBIAL
STEWARDSHIP LEADERS (USA)16 TOOLKIT RESOURCE
In the USA, the Society for Healthcare Epidemiology of ARTICLES
America partnered with other leaders in advancing the field of
17 Cosgrove, S., Hermsen, E., Rybak, M., File, T.,
antimicrobial stewardship, to develop a summary description
Parker, S., & Barlam, T. (2014). Guidance for
of the core knowledge and skills required for antimicrobial
the Knowledge and Skills Required for
stewardship professionals engaged with building, leading, and
Antimicrobial Stewardship Leaders. Infection
evaluating Antimicrobial Stewardship Programmes ().
Control and Hospital Epidemiology, 35(12),
The categories included were:
1444-1451. doi:10.1086/678592
• General principles of antimicrobial stewardship
• Approaches to stewardship interventions SITE LINK
• Antimicrobials
18 https://www.cdc.gov/getsmart/community/for-
• Microbiology and laboratory diagnostics
hcp/continuing-education.html
• Measurement and analysis
• Informatics/IT Program building and leadership
• Special populations and non-acute hospital settings
• Infection control
AN ANTIBIOTIC STEWARDSHIP EDUCATIONAL RESOURCES

CURRICULUM FOR MEDICAL STUDENTS17 Reducing Antimicrobial Resistance level 1 e-learning
A curriculum intended for use in U.S. medical schools. It is was developed in England to support all health and social care
comprised of: three didactic lectures with facilitator notes and staff – both clinical and non-clinical - in a variety of settings to
audio recordings, nine corresponding exam questions (available understand the threats posed by antimicrobial resistance, and
on request), and five small group activities with facilitator guides. ways they can help to tackle this major health issue.
The didactic lectures are geared toward medical students in the
pre-clinical years whilst the small group activities are geared
toward medical students on clinical clerkships
EUROPE
A European consensus: ESCMID generic competencies in
antimicrobial prescribing and stewardship
Currently, European Society of Clinical Microbiology and

Infectious Diseases is developing a Europe-wide consensus-
based set of generic competencies in antimicrobial prescribing
and stewardship that is relevant for all independent prescribers
across Europe.
No published competences have been located for any country

Africa or in Australia, India, China or South Africa.
VISIT SITE

CDC: Get Smart about Antibiotics A GP guide to antimicrobial resistance
A SHORT EDUCATIONAL VIDEO

FOR GENERAL PRACTITIONERS
WATCH VIDEO
Antimicrobial stewardship workbook for nurses:
VISIT SITE
TARGET toolkit for primary care

TARGET (Treat Antibiotics Responsibly, Guidance, Education,
Tools) resources aim to help influence health-workers,
prescribers’ in primary care and patients’ personal attitudes,
social norms and perceived barriers to optimal antibiotic
prescribing. It includes a range of resources that can each
be used to support health-workers, prescribers’ and patients’
responsible antibiotic use, helping to fulfil CPD and revalidation
requirements. The training resources are available for free and
can be accessed online by different health professionals, GPs,
trainee GPs, medical students, GP trainers, physician assistants,
practice nurses and non-medical prescribers.
VISIT SITE
VISIT SITE

Antibiotic Guardian The Prescribing Safety Assessment (PSA)

an educational and behaviour change intervention resource The Prescribing Safety Assessment (PSA) is an assessment
which asks health and social care professionals, leaders, required of all foundation medical trainees who have studied
students, educators and members of the public to choose one in UK medical schools or overseas. Over 40,000 students
of the available tailored pledges on how they plan to contribute and doctors have now benefited from taking part in both the
to tackling AMR. assessment and associated training materials. Currently 400
question items out of a total of around 3,000 (13%) cover
antimicrobial drugs and their usage.
VISIT SITE
PRESCRIBING SKILLS FOR

THE PSA EXAM FROM ELSEVIER
AND PODMEDICS
WATCH VIDEO
Antibiotic Guardian was developed as part of UK activities for
European Antibiotic Awareness Day (EAAD), and in support of
the UK 5-year AMR strategy.
The ScRAP Programme
Process and outcome evaluations for the Antibiotic Guardian an educational toolkit for primary to help prescribers to reduce
(AG) campaign performed and published in peer review unnecessary prescribing of antibiotics. It consists of: - A pre-
publications (BMC Public Health and Journal of Public Health) in recorded presentation that can be streamed online - Icebreaker
2016 showed the wide reach of the campaign and its success video - Patient Consultation video
in increasing commitment to tackling AMR in both healthcare
professionals and members of the public as well as leading to
increased knowledge and changed behaviours (self-reported
VISIT SITE
VISIT SITE
NICE
developed a free e-learning session on antimicrobial stewardship
targeted at commissioning and provider organisations, service
The prescribing simulator managers and local decision-making groups, to ensure that
is an online training environment that provides the opportunity effective antimicrobial stewardship programmes are in place,
for prescribers to practice in a simulated online environment at and that prescribers are supported to make changes to their use
any time or place. Users are presented with clinical scenarios of antimicrobials where necessary
that require a prescription on a certain prescription form. The
prescription is then automatically scored and feedback is
provided to guide the user as to where future improvements
can be made. VISIT SITE
VISIT SITE

AMSportal Do Bugs Need Drugs? (DBND) is a community education

is a free online forum collaboratively developed by The Royal program about handwashing and responsible use of antibiotics.
Pharmaceutical Society and the University College London Materials are available for healthcare professionals and the
and funded by Health Education England North Central and public that explain why antibiotic resistance is an issue and steps
East London, that signposts viewer’s to resources and to prevent antibiotic resistance from developing.
information to promote learning about microbiology and
VISIT SITE
VISIT SITE
Antimicrobial Resistance Learning Site for Veterinarians
open-source teaching modules are designed for integration into
BSAC AMR Portal existing veterinary school courses regarding: Pharmacology,
The antimicrobial resource centre (ARC) was developed by Microbiology,Public Health, and Species-specific medicine.
the British Society of Antimicrobial Chemotherapy as a global
repository of information for all people interested in the effective
management of infectious diseases
VISIT SITE
VISIT SITE
CANADA
The CPhA provides resources on the roles pharmacists can
play in antimicrobial stewardship, a webinar on stewardship for
common infections, and links to Canadian stewardship initiatives.
VISIT SITE
Antibiotic Stewardship Open Virtual Learning Committee

(European Society for Clinical Microbiology and Infectious
Diseases) - AS-OVLC is an open-access web-based resource
that has been created to provide information and tools to foster
antimicrobial stewardship among healthcare professionals.
(Twitter: @ESGAP_ABS)
VISIT SITE

Antibiotic Prescribing Game
VISIT SITE
“On call: antibiotics”, an electronic prescribing game to support

and encourage the prudent use of antimicrobials in acute care
was developed by researchers and clinicians at Imperial college.
“On call: antibiotics” allows doctors, nurses and pharmacists
to manage a series of virtual patients attending a simulated
hospital. Racing against the clock and the increasing workload,
players receive information about the symptoms experienced
by patients and have to diagnose and manage the cases. To be
successful, players have to make optimal use of antibiotics and
antibiotic prescribing behaviours.
The game provides immediate feedback on players’

performance and decisions, considering clinical accuracy
and the impact on other professionals and the wider hospital
environment.

CHAPTER 14
AUTHOR: MARC MENDELSON
ANTIBIOTIC STEWARDSHIP
EDUCATION IN LOW
RESOURCE SETTINGS
LEARNING OUTCOMES
CHAPTER IS TO:
• Learners will assess the available educational resources in their setting and the need to
To review the educational expand their concept of who delivers antibiotic stewardship education in countries with
resources predominately a lack of infection specialists.
developed by, and applicable
to, low and middle-income
countries. RECOGNISING A PROBLEM
Studies of knowledge, attitude and practice in undergraduate health students from high
resource settings relating to antibiotic resistance (ABR) and antibiotic stewardship (ABS)
have repeatedly demonstrated that the prescribers of tomorrow are inadequately prepared
to prescribe and optimally administer antibiotics. The few similar studies from low- and
middle-income countries (LMIC) concur; In South Africa, only one third of final-year medical
students from 3 of the country’s top medical schools felt confident to prescribe antibiotics,
and 95% recognised their need for better education in ABR/ABS (Wasserman 2017).
Similarly, only one third of final-year South African pharmacy students remembered having
had formal stewardship teaching, yet 90% desired it (Burger 2016). Postgraduate education
too, needs improving; almost all of those questioned in a Brazilian study, believed ABR was
an important problem, only 3% felt that practicing stewardship was important (Guerra). All
too often, ABR is seen as someone else’s problem, and hence understanding of the need to
become better educated in stewardship, is lost.
THE CHALLENGE
Staffing shortages, fragmented health systems, and lack of infection specialists across the
health professions who can teach stewardship, impose significant challenges on delivering
antibiotic stewardship education in LMICs. Furthermore, due to stretched service delivery,
apportioning time for stewardship education for postgraduate health care professionals can
cause further tension in the system.
MAKING THE MOST OF WHAT IS ALREADY OUT THERE

In view of these challenges, LMICs need to make use of what is already out there,
especially online educational opportunities which have become increasingly accessible
through developments in global information and communications technology (Figure 1).

CHAPTER 14 - ANTIBIOTIC STEWARDSHIP EDUCATION IN LOW RESOURCE SETTINGS
FIGURE 1
Global trends in mobile cellular telephone subscriptions and internet usage
Image by kind permission International Telecommunications Union
With the massive scale of social media and other content (There are also ‘one-stop-shop’ websites providing literature,
creation that happens on the web every minute (Figure 2), social media-based tools and twitter chats such as the University
there are clearly huge opportunities for online learning. of Minnesota’s Center for Infectious Diseases Research and
Policy (CIDRAP) website
VISIT SITE
VISIT CIDRAP SITE
Opportunities include access to comprehensive stewardship
or The ReAct toolbox,
courses either developed in high income settings but applicable
globally, such as:
VISIT ReACT SITE

BSAC’S MASSIVE ONLINE
OPEN COURSE which contains a number of educational videos highlighting why
stewardship is important.
WATCH VIDEO
ReAct toolbox
or those developed in, and specifically directed towards, the
WATCH VIDEO
LMIC-setting, such as the South African Antibiotic Stewardship
Programme (SAASP) Open Learning course:
The World Health Organisation too, is developing an active

Community of Practice, to support a discussion forum around
VIEW SLIDE SET development of national action plans, which will include
educational resources. Further stewardship educational
programs developed in low resource settings, which are freely
available are outlined in Table 1.

PROGRAMME LEAD ORGANISATION COUNTRY TARGET AUDIENCE DESCRIPTION

Clinical Antibiotic South African Antibiotic South Africa Medical Students Free, self-paced online course
Stewardship for Stewardship Programme Physicians introducing AMS, describes how to
South Africa implement ASPs, & provide guidance
for prescribing and interpreting clinical
results, and teach about IPC.
South African Antibiotic South African Antibiotic South Africa Medical Students Free algorithmic antibiotic prescribing
Stewardship Prescribing Stewardship Programme Physicians guidelines App, hosted on the Essential
Guidelines for Adults Pharmacists Medical Guidance (EMG) platform.
Includes training on stewardship
principles & approach, as well as
guidelines for specific infections
Distance Learning Infection Control Africa Physicians, 3.5-month online distance learning
Course in Antimicrobial Africa Network Pharmacists course - 5 modules relating to
Stewardship for Africa Microbiologists infectious diseases; one focused on
Nurses AMS. Lectures, reading materials, &
discussion forums to engage with
tutors & other students. Free for African
participants.
Online Rational University of Western South Africa Health Care Single semester online course with
Medicines Use module Cape Professionals weekly tasks, discussion forums &
written assignments
Antibiotics Smart Use AMR Containment Thailand Health Care Country-wide education campaign
Program in Thailand Professionals, for prescribers. Shared experiences,
Patients, Public treatment guidelines, diagnostic
tools, patient education tools (DVDs,
pamphlets & other materials)
ASPIC (Antibiotic Indian Council of India Pharmacists 5-day workshop of lectures, site
Stewardship, Prevention Medical Research Microbiologists visits, practical training focusing on
of Infection & Control) IPC, implementation of antimicrobial
policy guidelines, conducting research
projects in antibiotic policy
Dept of Health Manual Philippines Dept of Philippines Physicians Operational guide and reference for
of procedures for Health & WHO developing training programs and
implementing AMS in materials
hospitals
Training-of-Trainers Philippines Dept of Philippines Health Care Interactive session on current initiatives
Workshop on AMS Health & WHO Professionals & challenges of each hospital in relation
Advocacy Training to IPC, rational use of antimicrobials
and surveillance of AMR. Also included
was a consultation on draft AMS pilot
program implementation.
Training-workshop Philippines Dept of Philippines Physicians AMS program with an educational
for government Level Health & WHO Corazon component piloted at Philippine
III hospitals on the Locsin Montelibano General Hospital
implementation of the Memorial Regional and Corazon Locsin Montelibano
AMS Hospital Memorial Regional Hospital, now scaled
up to provide training at all Dept of
Health level III hospitals
TABLE 1
Antimicrobial stewardship educational programmes developed by low-and middle-income countries. AMS – Antimicrobial Stewardship; ASP –
Antimicrobial Stewardship Program; IPC – Infection Prevention & Control. Adapted from Susan Rogers Van Katwyk; Sara L Jones; Steven J Hoffman.
Mapping educational opportunities for healthcare workers on antimicrobial resistance and stewardship around the world. Human Resources for Health
(In Press).

EDUCATING HEALTH CARE it needs to be adapted in settings deprived of infection

PROFESSIONALS IN LOW RESOURCE specialists. This is being done in South Africa, where two
SETTINGS – A HOSPITAL-BASED national training centres provide tools
APPROACH
It is generally accepted that education programmes should
be combined with strong stewardship interventions for VIEW SLIDE SET
maximal effect, and not be delivered in isolation. Developing
postgraduate education programmes for health care
professionals in LMICs must take into account how stewardship
and practical training programmes for non-infection specialist
will be delivered in a low resource setting with few trained
teams from hospitals throughout the country. A team of a
infection specialists and will need to adapt the traditional
prescriber-pharmacist-nurse manager from each hospital,
concept of who the opinion leaders are that can influence
receive practical education on how to perform stewardship
adoption of good prescribing practice in low resource setting.
rounds in a variety of settings (wards, intensive care units,
While multidisciplinary hospital teams led by infectious diseases
academic and district-level hospitals), diagnostic stewardship
specialists, microbiologists, infectious diseases pharmacists and
taught on laboratory rounds, and small group sessions (Figure 3)
infection prevention control specialists may be achievable in
to cover essential pharmacology, and optimising use. These non-
high income countries and few individual hospitals in LMICs that
specialist teams then set up antibiotic stewardship programmes
have trained staff
in their hospitals, and receive ongoing mentorship from their
National Training Centre.
VIEW DOCUMENT
FIGURE 3
South African National Antibiotic Stewardship Training Course
comprises practical stewardship ward and intensive care unit rounds,
small group discussions, and laboratory teaching

An equally successful, sustainable reduction in antibiotic use

has been achieved across a South African private hospital
group employing non-specialist pharmacists trained in a simple TOOLKIT RESOURCE
stewardship intervention targeting 4, low-hanging fruit changes
in prescribing.
ARTICLE
Guerra CM, Pereira CA, Neves Neto AR, Cardo
DM, Correa L. Physicians’ perceptions, beliefs,
attitudes, and knowledge concerning antimicrobial
VIEW DOCUMENT resistance in a Brazilian teaching hospital. Infect
Control Hosp Epidemiol 2007;28(12):1411-1414
A collaborative programme of mentorship of South African SITE LINK

pharmacists by U.S. Infectious Diseases specialist pharmacists
Wasserman S, Potgieter S, Shoul E, Constant
has been instrumental in developing pharmacists as valued
D, Stewart A, Mendelson M, Boyles TH. South
antibiotic stewards in South Africa, and serves as an example
African medical students' perceptions and
of the value of collaborative educational programmes and
knowledge about antibiotic resistance and
partnerships between LMICs and high-income countries.
appropriate prescribing: Are we providing adequate
training to future prescribers? S Afr Med J. 2017 Apr
25;107(5):405-410. doi: 10.7196/SAMJ.2017.
v107i5.12370. PMID: 28492121
VIEW DOCUMENT
Burger M, Fourie J, Loots D, Mnisi T, Schellack
N, Bezuidenhout S, and Meyer JC. Knowledge
Developing nurse- and community health worker-led models and perceptions of antimicrobial stewardship
of care in LMICs would further expand the potential models of concepts among final year pharmacy students
stewardship and the needs for these cadres to receive role- in pharmacy schools across South Africa. Southern
specific education and training. Successful task shifting of African Journal of Infectious Diseases 2016;
antiretroviral management from doctors to primary health clinic 31(3):84–90
nurses (Fairall et al.) is a good example of how nurses in low
resource settings can play a greater role in stewardship.
Fairall L, Bachmann MO, Lombard C, et al. Task
shifting of antiretroviral treatment from doctors
to primary-care nurses in South Africa (STRETCH):
a pragmatic, parallel, cluster-randomised trial.
Lancet. 2012 Sep 8;380(9845):889-98.

CHAPTER 15
AUTHORS: DEBBIE GOFF, CELINE PULCINI, MUSHIRA ABDULAZIZ ENANI, KHALID ELJAALY, KIRSTY BUISING & ARJUN RAJKHOWA
STEWARDSHIP IN
DEVELOPED COUNTRIES
LEARNING OUTCOMES
CHAPTER IS TO:
• Explain the pharmacists’ role in the use of rapid diagnostic tests in the hospital setting
To provide 2 examples of • Define interventions by a pharmacist in the management of S. aureus bacteremia
successful stewardship
• Demonstrate basic awareness of stewardship initiatives running in European countries.
initiatives from a large
academic medical center in • Demonstrate skills for initiating prospective audit with intervention and feedback and
North America. preauthorization in limited resources setting
• Demonstrate awareness of surveillance programs and stewardship initiatives in Australia
To present an overview of
interesting and successful
stewardship initiatives in
European countries. NORTH AMERICA
Example 1: Role of Pharmacist in Management of Patients with S. aureus bacteremia
To describe the current status
of antimicrobial stewardship Ideally, every stewardship program should employ an ID pharmacist with formal ID training
programs, challenges gained through completion of an accredited post-graduate residency or fellowship in ID.
& opportunities in Gulf In the United States there are only about 400 pharmacists with formal post graduate ID
Cooperation State training. With more than 5,000 hospitals the reality of having an ID-trained pharmacist
Countries (GCC). at every hospital is a challenge. Therefore it is necessary for antimicrobial stewardship
programs (ASP) to utilize the talent of all pharmacists.
To share success stories of An established ASP in a 1,400 bed teaching hospital with ID pharmacists implemented
implementing stewardship a program utilizing all pharmacists to assist in the management of patients with
in the Gulf region. Staphylococcus aureus bacteremia (SAB) 24 hours a day 7 days a week. Based on previous
internal data, all patients with SAB were not being optimally managed, therefore ASP
To present an overview of
proposed a study to implement a pharmacist driven bundle approach. After obtaining
national surveillance programs
support from the Division of ID and approval by the Pharmacy and Therapeutics committee
and stewardship in Australia.
the proposal became hospital policy.
When a blood culture turned positive and the rapid diagnostic test identified SAB,
pharmacists were alerted via the electronic medical record 24/7. They would evaluate
compliance with 4 components in the SAB bundle and make interventions if necessary.
To illustrate an example of pharmacists using a bundle approach to manage patients with

Staphylococcus aureus bacteremia (SAB) you may wish to listen to this podcast. As you
listen to the podcast consider the following

CHAPTER 15 - STEWARDSHIP IN DEVELOPED COUNTRIES
• What are the four metrics that make up the bundle?
• What was the impact on mortality of the pharmacist driven

management of SAB bundle?
TOOLKIT RESOURCE
• How could you apply this program at your hospital to help
SITE LINK
improve the management of patients with SAB? An Automated, Pharmacist-Driven Initiative
Improves Quality of Care for Staphylococcus
aureus Bacteremia
VIEW SLIDE SET
THESE STUDIES PROVIDE EXAMPLES OF
PHARMACISTS USING RDT
Example 2: Role of Pharmacists in Rapid Diagnostic Tests
Controversies in Antimicrobial Stewardship:
A pharmacist has multiple roles in an antibiotic stewardship Focus on New Rapid Diagnostic Technologies
program. One of the key roles can be helping to implement and Antimicrobials
a rapid diagnostic test (RDT). A RDT without ASP can be a
waste of money when the physician does not act on the results Review of Rapid Diagnostic Tests Used by
rapidly. The pharmacist can use the RDT result to make sure Antimicrobial Stewardship
the patient is on the most effective antibiotic based on local
hospital guidelines. For example if the RDT identifies methicillin Impact of rapid identification of Acinetobacter
susceptible S. aureus and the patient is on vancomycin, the Baumannii via matrix-assisted laser desorption
pharmacist can recommend switching vancomycin to cefazolin or ionization time-of-flight mass spectrometry
nafcillin. The ASP metric to collect for this intervention is time to combined with antimicrobial stewardship in patients
effective therapy. with pneumonia and/or bacteremia
Several studies have show that a RDT with ASP involvement An Antimicrobial Stewardship Program’s Impact
shortens the time to effective antibiotic therapy. Some with Rapid Polymerase Chain Reaction Methicillin-
studies have also shown a mortality benefit. The key to Resistant Staphylococcus aureus/S. aureus Blood
successful implementation within a hospital is to make sure Culture Test in Patients with S. aureus Bacteremia
the microbiologist and ASP pharmacist work together. This
infographic demonstrates the 4 steps to implementing a RDT and
how a pharmacist provides an important role in the process.
1. The microbiologist can identify and evaluate new RDT. They

need to make sure the instrument can be incorporated in the
current work flow within the lab.
2. The ASP pharmacist can evaluate the potential impact of

the RDT on patient care. For example, if SAB RDT is being
considered the first step is to identify how many patients at
your hospital have SAB. The microbiologist can provide this
data. Next the pharmacist should identify the “time to
effective antibiotic therapy”. In hospitals using standard
culture methods without a RDT, the time to effective therapy
can be as long as 3-4 days.
3. Once the ASP team has decided to implement a RDT, the

pharmacist should work with the microbiologist to provide
education to the medical staff. Just sending an email or
posting an announcement in a new letter is often not enough.
4. The ASP pharmacist can make interventions and collect data

such as time to effective antibiotic therapy to document the
impact on patient care.

EUROPE and 2017 EU guidelines on prudent use of antimicrobials in

humans:
Europe is a great resource for antimicrobial stewardship, and
it offers a huge diversity in culture and health systems. Most
stewardship initiatives were started more than 20 years ago.
Being aware of stewardship programmes in Europe can then be
VIEW PRUDENT USE
a source of inspiration. OF ANTIMICROBIALS
Stewardship initiatives at the European level
DOCUMENT
ESGAP
ESGAP is the ESCMID (European Society of Clinical Microbiology Other useful documents summarising the progress made in
and Infectious Diseases) Study Group for Antimicrobial European countries:
stewardship (https://www.escmid.org/index.php?id=140). A
summary of ESGAP activities is presented here:
VIEW AMR REPORT DOCUMENT

VIEW SLIDE SET
ECDC VIEW BEST PRACTICE ARTICLE

The European Centre for Disease Prevention and Control (http://
ecdc.europa.eu/en/Pages/home.aspx) has relentlessly worked to
combat antimicrobial resistance (AMR). A selection of ECDC most
prominent stewardship actions is detailed here: WHO-Europe
WHO regional office for Europe includes EU member states

as well as many other European countries. It has done much
VIEW SLIDE SET to improve antibiotic use : useful resources, promotion of the
World Antibiotic Awareness Week, country visits and educational
courses, publications…
More information is available here:

European Commission
The European Commission has issued a number of reports and
guidance documents, and has done much to curb antimicrobial
resistance, with a second 2017 European action plan on AMR : VISIT SITE
VISIT SITE E-Bug programme
E-Bug has developed wonderful (free access) teaching resources

about microbes and antibiotics, initially developed to teach
children and teenagers, but the scope has expanded over the
VIEW AMR ACTION years : http://www.e-bug.eu
PLAN DOCUMENT
VISIT SITE

or in Scotland in the UK
VISIT SITE
Restrictive measures
Restrictions on antibiotic prescribing are commonplace in
hospitals, but are quite rare in primary care. In Slovenia, co-
amoxiclav, fluoroquinolones, oral 3rd generation cephalosporins
and macrolides’ prescriptions are audited in the outpatient
setting, and prescribers are fined if their prescriptions do not
comply with national guidelines.
Accreditation/Certification of hospitals
For example in France, implementation of an antibiotic
stewardship programme (assessed using a composite indicator,
Examples of successes at national level
A few national or regional initiatives are cited below as examples

to illustrate a specific stewardship intervention. This is far from VIEW DOCUMENT
being exhaustive.
1. Interventions at the health system level

is mandatory in hospitals to get accredited.
Antibiotic stewardship cross-sectoral networks
Pay-for-performance
In some countries, such as Sweden;
Some countries, such as France
VIEW CONTAINMENT OF
ANTIBIOTIC RESISTANCE VISIT SITE
DOCUMENT
or the UK in hospitals
or France;
VISIT SITE
VIEW SITE
and in primary care:
antibiotic stewardship programmes are implemented in different
settings (hospital, primary care, long-term care facilities) and at
local, regional and national levels. This is also done at a regional
level in Andalusia in Spain;
VISIT SITE
have introduced pay-for-performance systems linked to antibiotic

VISIT SITE use targets, and this has led to a decrease in
antibiotic use.

Public reporting
In England, the data on antibiotic consumption and resistance
for both hospitals and primary care are publicly available on a VIEW SWAB-ID GUIDE
website:
Public commitment
VISIT SITE In France, prescribers are encouraged to show their public
commitment to prescribe antibiotics responsibly, by displaying a
poster in the waiting room
2. Interventions targeting healthcare professionals
Education
Many educational resources are available. Let us cite the VISIT SITE
Massive Online Open Course on Antimicrobial Stewardship
produced by the British Society for Antimicrobial Chemotherapy
Practical tools for antimicrobial stewardship teams
Most countries are now sharing these at national level, such
VISIT SITE as in France;
In Germany, a 4-week training programme to become a certified VISIT SITE

‘ABS-expert’ has been running for some years, and an ABS-
network facilitates exchange of experience among antimicrobial
stewards. or in the Netherlands;
VISIT SITE VISIT SITE
The University of Antwerp (Belgium) has developed practical

Guidelines tools (with a free e-learning module) for point-prevalence
surveys.
Guidelines helping prescribers choosing the best antibiotic
regimen exist in almost all countries. In the Netherlands, SWAB
(The Dutch Working Party on Antibiotic Policy) introduced an
electronic national antibiotic guide 'SWAB-ID' for the antibiotic
treatment and prophylaxis of common infectious diseases in
VISIT SITE
hospitals;
3. Interventions targeting the general public

VIEW DOCUMENT Public awareness and information campaigns
A recent review has been published:
Every hospital in the Netherlands has been offered the

opportunity to adapt this version to local circumstances and VIEW DOCUMENT
resources and distribute it through an independent website.
At present, approximately 60 % of Dutch hospitals uses a local,
customised version of SWAB-ID.

Information documents
- Non-prescription pads in France
TOOLKIT RESOURCE
SITE LINK
VIEW DOCUMENT ECDC
French ID society
or in the UK
Dutch Ateams
VIEW DOCUMENT ReACT Group
BSAC ARC
- Lots of other information documents have been developed in

many countries, for example in the UK
GULF COOPERATION STATES

VISIT SITE Antibiotic misuse is a major determining factor of Antimicrobial
Resistance (AMR), occurring in around 50% of prescribing (CDC
report, antibiotic resistance threats in the United States 2013).
Gulf Cooperation States (GCC) countries are facing challenges
Other interventions of emerging antimicrobial resistance. The examples listed
The Antibiotic Guardian campaign was launched in 2014 in below are practical interventions undertaken to try and address
the UK (http://antibioticguardian.com). It encourages everyone this issue.
to become an antibiotic guardian, and to choose a pledge to
demonstrate his/her public commitment to responsible GCC Point Prevalence Survey to understand ASP Practices
antibiotic use. A web-based survey was conducted in 2015 addressed to GCC
countries namely, Saudi Arabia, UAE, Bahrain, Oman, Qatar, and
Kuwait. There were a total of 44 responses from 4 GCC countries
as follows: Saudi Arabia 38/47 (80.9%), UAE, Oman, & Bahrain
6/47 (19.1%)
Twenty-nine out of the participating hospitals (66 %) had ASP in

place; the majority of these were tertiary care teaching hospitals
with 200-800 bed capacity. Of the 44 responses the top three
objectives were to reduce resistance, improve clinical outcome
and reduce costs (Table 1). Preauthorisation and restricted list
of antimicrobial agents appeared to be the core stewardship
strategy practiced in GCC countries (Figure 1).
SETS OF OBJECTIVES FREQUENCY (44

VISIT SITE OF ASP RESPONSES)
Improve clinical outcome 75%
Minimise or stabilize 77%
resistance
Reduce cost 47.7%
Reduce C.difficile infection 13.6%
TABLE 1 - Objectives of ASP in GCC Reduce length of stay 2.3%

In some hospitals, barriers to ASP were identified these are

shown in Table 2.
PREAUTHORISATION BARRIERS PREVALENCE

(91%) Hospital administration not aware 9%
Lack of personnel or funding 23%
Multiple factors 52%
ANTIMICROBIAL AUDIT Obstruction from prescribers 11%
(68%) Others 11%
TABLE 2
Barriers to effective antimicrobial Stewardship (out of 44 responses)
ANTIMICROBIAL FIRST CHOICE
AND DOSING GUIEDLINES
(27%)
READ THE FULL PAPER
FIGURE 1
Top three strategies of ASP in GCC (out of 44 responses)
A noticeable finding of GCC survey was the reported favourable

impact on patients and hospitals after initiation of ASP; these
were around reduction in healthcare-associated infection,
inappropriate antibiotic prescribing, length of stay or mortality
metrics and antimicrobial resistance, Figure 2.
73%
REDUCTION OF INAPPROPRIATE
ANTIBIOTIC USE
66%
REDUCTION OF HEALTHCARE-
ASSOCIATED INFECTION
59%
REDUCTION IN AMR
FIGURE 2

The clinical pharmacist Files of patients on Cl. Pharmacist reviews Data collection sheet
prints list of patients systemic antimicrobials patient's files on day 1, designed incorporating
receiving systemic from 3 medical & 1 3, and 7 ; interventions the antibiotic
antibiotics in surgical wards discussed with ID care bundle
specific wards were audited consultant or fellow
CLICK HERE FOR A COPY

OF THE DATA COLLECTION
SHEET
Saudi Arabia Experience • Communication opportunities to increase effective dialogue

between the primary team & antimicrobial stewardship team,
Example 1 (above): Prospective audit with intervention and
which has developed a culture of trust.
feedback in Adult Medical & Surgical Wards at King Fahad
Medical City Within the first 3 months of implementing the antimicrobial
stewardship programme compliance to ASP recommendations
A total of 602 patients on antibiotics were reviewed with 310
improved from 12 to 43% with documentation of duration further
requiring the following interventions Figure 3.
improving by 46%.
Example 2: Implementing pre-authorisation to reduce key

antibiotic agents
Discontinue
27% In a tertiary medical center in Saudi Arabia, there were several
IVt o PO Switch challenges around managing the treatment of gram negative
51% bacteria. These included the wide spread use of colistin
De-escalate/change
and tigecycline, a lack of ASP policies and minimal infection
16% Specify duration specialists. The hospital invited an ID pharmacist trained in ASP
to help create an AS programme initially looking at a restriction
5% system around key antibiotics and selective microbiology
reporting. Four ID assistant consultants were hired to help the
These interventions resulted in a primary ID consultant and pharmacist. Click here to listen to the
challenges faced and interventions deployed.
• Behavioural change & better prescriber’s awareness of the
need to specify the antimicrobial duration from the time of
prescription, which has subsequently reduced the cost of top
3 prescribed antibiotics (piperacillin-tazobactam, ceftriaxone,
& carbapenem) by 360,000 Saudi Riyals per year.
DOWNLOAD SLIDE SET
• Education opportunity to avoiding antibiotics when the
evidence of bacterial infection is lacking.

Colistin and tigecycline were switched from being widely Example 3: Saudi Arabian Ministry of Health initiative
available to being under restriction. Colistin use decreased
As per the directive of his Excellency the Saudi Minister of
by 60% and it was associated with significant reduction in
Health, the General Directorate of Infection Prevention and
Acinetobacter resistance from 31% to 3% in a year. Tigecycline
control has formulated a national AMR committee to meet the
use decreased by 46%, while carbapenem use and associated
global action plan to combat microbial resistance. Five technical
resistance stayed the same, which could be attributed to
committees reporting to the national AMR have completed the
switching from colistin.
national road map to combat AMR.
COLISTIN USE VIEW DOCUMENT

1368 554
60% Among the ambitious objectives of stewardship committee is

mandating antimicrobial stewardship education in medical,
nursing, & allied sciences’ curricula to improve knowledge, skills,
REDUCTION
and attitudes toward antimicrobial prescribing. This document
was further been incorporated into a wider WHO report of Saudi
Arabia;
ACINETOBACTER
RESISTANCE TO TOOLKIT RESOURCE
COLISTIN ARTICLES
Alawi MM, Darwesh BM. A stepwise introduction
of a successful antimicrobial stewardship program.
Experience from a tertiary care university hospital
in Western, Saudi Arabia. Saudi Med J.
2016;37(12):1350-1358
2013 2014 2015 2016
28%REDUCTION
Enani M, The Antimicrobial Stewardship Program
in Gulf Cooperation Council (GCC) States: Insights
from a regional survey Journal of Infection
Prevention, Oct 2015: 1-5
TIGECYCLINE Amer MR, Akhras NS, Mahmood WA, Al-Jazairi AS.
458 246 Antimicrobial stewardship program implementation
46%
in a medical intensive care unit at a tertiary care
hospital in Saudi Arabia. Ann Saudi Med.
2013;33(6):547-54.
REDUCTION Bahrain Experience
The Ministry of Health covers 80% of health services in Bahrain.

Antimicrobial stewardship was introduced within Bahrain in 2010
in Al-Salmanyia Medical Centre.
To view the challenges and opportunities of Bahrain’s

antimicrobial stewardship programme:

• Most tertiary hospitals have dedicated staff resources for

AMS. These members of staff, often called ‘AMS teams’, tend
VIEW SLIDE SET to do the day-to-day work of prescription review, education
and auditing.
• AMS teams at the bigger hospitals are primarily led by

infectious diseases physicians and clinical pharmacists. At
Acknowledgement smaller sites, non-ID-expert medical, pharmacy and nursing
Hail Al Abdely, DG of infection prevention & control, chair, Saudi staff are leading programs. There is growing awareness of the
national AMR committee, Ministry of Health; importance of building capacity and involving all healthcare
staff in AMS as part of everyday work.
Areej Malhani, Clinical Pharmacist & Stewardship committee
coordinator, KFMC; A number of studies have evaluated and demonstrated the
impact of AMS programs in Australian hospitals.
Maha Alawi, Infectious diseases & Stewardship leader in KAUH,
Jeddah; Auditing is clearly necessary for monitoring adherence to
recommendations, identifying areas that need intervention and
Jameela Al Salman, Infectious Diseases Consultant & driving improvement.
Stewardship leader in Bahrain
• In Australia, surveillance of antimicrobial consumption in
hospitals has been undertaken since 2004 through the
AUSTRALIA National Antimicrobial Utilisation Surveillance Program
Australia has been an early adopter of antimicrobial stewardship, (NAUSP). This program has allowed the tracking of changes
with some areas of demonstrated success. in consumption over time and some limited comparisons
between hospitals. However, it is important to note that
• One key area of success has been the development and
participation is voluntary, and adjustment of data according to
implementation of national antimicrobial prescribing
hospital case-mix is not available, so analysis and
guidelines, called Therapeutic Guidelines: Antibiotic (available
comparisons must be undertaken with caution. Involvement
since 1978). They cover hospital and community prescribing,
in NAUSP increased after the new accreditation standards
and are well respected and widely endorsed.
were released. In 2014, 129 hospitals contributed data
• In 2015, the importance of these guidelines was further (representing 82% of beds from hospitals of greater than 50-
augmented by their inclusion in both the National Standards bed size). The NAUSP data have demonstrated a small
for Hospital Accreditation and the Clinical Care Standards for decline in hospital antimicrobial consumption (-6.2%
Antimicrobial Stewardship. DDD/1000 OBD) from its peak in 2010. Consumption
• In 2011, the Australian Commission on Safety and Quality in measured by defined daily doses per 1000 occupied bed
Healthcare (ACSQHC) published recommendations for what days appears to be higher than Sweden and on par with
was expected of programs for AMS in Australian hospitals, Denmark.
and, in 2013, for the first time, evaluation of the quality of • In addition, there is a program called the National
the AMS programs was included in accreditation standards Antimicrobial Prescribing Survey (NAPS). This is a
for hospitals. comprehensive program that was first developed in 2011, and
• Hospitals were required to show that they had antimicrobial in 2016 involved >400 hospitals (with >25,000 prescriptions).
prescribing policies in place (usually incorporating a formulary The annual audit activity is a point prevalence survey of
with restrictions), and that auditing was occurring and clinical antimicrobial use across inpatients in hospitals. The audit
improvement activities were taking place. assesses both concordance with guidelines and
appropriateness of prescribing. The rollout of this audit has
Most larger hospitals now have established AMS committees to been accompanied by extensive training to enable auditors
oversee the hospital’s AMS activities. to assess appropriateness in a consistent manner, and the
• Established AMS programs at Australian tertiary hospitals use of appropriateness as a measure has been important in
are multifaceted and use a multi-pronged approach, gaining clinicians’ acceptance of the findings (appreciating
combining elements such as formulary control; the use that guidelines do not always apply to individual patients).
of decision-support and approval systems; post-prescription
review; clinical consult rounds; education and workforce
training; and auditing with feedback.

FIGURE
Examples of the National Antimicrobial Prescribing Survey (NAPS) reports (image credit: Australian Commission on Safety and Quality in Health Care
[ACSQHC]), and education and training activities undertaken by the National Centre for Antimicrobial Stewardship (NCAS).
Participation in the NAPS audit has become part of hospitals’ modules focused on target areas, such as the Surgical NAPS
training and education for staff, with experts within the and the Hospital-in-the-Home (HITH) NAPS, have also been
NAPS program routinely providing clinical information and developed and deployed.
assessment support to hospital auditors. The program’s focus
The Clinical Care Standards for Antimicrobial Stewardship were
on appropriateness of prescribing has required and facilitated
developed by the ACSQHC in 2016 and are intended to describe
the dissemination of key information and assessment skills
appropriate practice at an individual patient level. They are a
to these critical personnel, thereby directly informing clinical
powerful description of what ‘good care’ should look like in
improvement activities in hospitals. The NAPS also enables
relation to safe, high quality antimicrobial drug use.
hospitals to instantaneously generate their hospital-specific
report and benchmarking (comparison with peer-group hospitals) Activity around AMS in the community has arguably lagged
report following data-entry. This facilitates the quick utilisation of behind activity in hospitals. Australia is a high consumer of
data for quality improvement activities. antibiotics in the community relative to other OECD countries.
Data on antimicrobial use in the community largely come from
Areas of problematic prescribing in hospitals have been
the Pharmaceutical Benefits Scheme (PBS). This is a program
identified over the years, leading to more focused activities.
through which the Commonwealth government subsidises
The NAPS 2015 report provides the latest published results as
medication costs in the community. It governs the reimbursement
well as an overview of the previous years’ findings. Importantly,
of costs for a specified list of drugs and indications, and thus
the NAPS program is unique in that it assesses concordance
functions as a formulary with restrictions (restricting access to
with guidelines and appropriateness of prescribing on a national
fluoroquinolones, for example).
scale. Drawing on the annual surveys’ findings, additional

The NPS MedicineWise program has been funded by the

Antimicrobial Prescribing in Commonwealth government to support education for general
practitioners, and provides evidence-based information free
Major City Public Hospitals from the influence of pharmaceutical companies. It is likely that
there is much scope to further develop AMS activities in the
The
prevalence of community to address the high consumption rates and poor
antimicrobial Major City Hospitals have concordance with evidence-based recommendations that have
use in the lowest percentage of been described in some studies.
Australian major inappropriate
city public
antimicrobial prescribing Auditing of antimicrobial use in the community has been
hospitals is
38% The most somewhat limited by an inability to link the indication for use
inappropriately to the individual prescription. Early data are emerging from a
prescribed indications are;
program called MedicineInsight, in which data are electronically
 infective exacerbation
of asthma, COPD extracted from medical records.
and bronchitis
 surgical Data from primary care settings are suggesting that usage
prophylaxis The most is poorly compliant with recommendations, particularly for
 fever of unknown
inappropriately
prescribed antimicrobials are;
respiratory infections. Studies focused on appropriateness of
origin
 cephalexin
antimicrobial prescribing in the community as well as prescriber
 clarithromycin knowledge and perceptions are being piloted.
The most  roxithromycin
common reason
 cephazolin
One area where detailed information is emerging is the
for inappropriate
prescribing was
 amoxycillin-clavulanate residential aged care sector. In 2015, an aged care NAPS
antimicrobial (acNAPS) was conducted across 186 residential aged care
spectrum too
facilities (RACFs), and was able to identify several key areas of
broad
inappropriate prescribing.
Data derived from the 2015 Hospital National Antimicrobial Prescribing Survey
• A high level of antibiotic use among residents was noted,
with a significant proportion (22%) of antimicrobials
prescribed for prophylaxis.
Antimicrobial Prescribing in
• It was found that prescriptions were often continuing beyond
Surgical Procedures 6 months.
• Urinary infections and skin and soft tissue infections figured

33% of surgical episodes
had inappropriate peri-
most highly amongst the indications for prescription.
operative prophylaxis,
40% of all FIGURE
surgical episodes had most common reasons for
inappropriateness were Aged Care National
inappropriate
surgical prophylaxis incorrect timing and Antimicrobial
incorrect dose Prescribing Survey
(2016).
Image credit:
Where post-operative
antimicrobials were
ACSQHC
22% of all surgical
prescribed, 60% were
episodes had
inappropriate inappropriate,
post-operative most common reasons were
prophylaxis incorrect dose and incorrect
duration
Surgical NAPS
75 hospitals
participated
Comprising 3800
surgical episodes
Data derived from the 2016 Surgical National Antimicrobial Prescribing Survey

FIGURE
Poster highlighting data from the Aged Care National Antimicrobial
Prescribing Survey (2015). Image credit: ACSQHC.

In 2013, the ACSQHC began a program called AURA, which

focused on collating data from cross-sectoral surveillance of
antimicrobial usage and resistance. The 2016 and 2017 AURA
reports drew on existing programs (NAUSP and NAPS) as well
as enhanced laboratory surveillance data to produce useful
snapshots of the current state of play.
It has been recognised that surveillance must be accompanied

by action to address the problems that are identified. Australia’s
first National Strategy to address antimicrobial resistance was
released in 2015, and, importantly, took a “one health” approach,
incorporating animal and human health. This was followed by an
implementation plan that detailed activities for the coming years.
Some elements of this plan build on existing initiatives that have

successfully driven improvement.
• In hospitals, one example has been the use of computerised

workflow-based tools to support AMS programs. Australian
hospitals have been early adopters of these tools, and
independent evaluations have suggested good uptake and
an association with improved prescribing.
FIGURE
• Workflows that incorporate both pre-prescription approval Antimicrobial Use and Resistance in Australia Report (2017). Image
and post-prescription review by multidisciplinary AMS teams credit: ACSQHC.
are now common in tertiary hospitals.
• Workforce capacity building has been undertaken by groups

such as the National Centre for Antimicrobial Stewardship
through education and training. This same group conducts the
NAPS and has undertaken research on sustainable
interventions to improve prescribing behaviours.
In the Australasian region, New Zealand is another country

where initiatives to tackle AMR have made some progress.
• In 2017, the Health Quality & Safety Commission commenced

the development of a national action plan for AMR.
• Antimicrobial consumption in the community has been

assessed by some studies, and the use of extended-spectrum
penicillins (particularly among children and Pacific
communities) and topical antibiotics appears to be high.
• A few New Zealand hospitals participate in the Australian

NAPS, generating hospital-specific reports rather than
contributing to Australia’s national surveillance program.
• No AMS-specific accreditation standards currently exist but

clinical groups have been progressing plans in this area.
While Pacific nations currently do not have surveillance systems

in place to monitor antimicrobial use and AMR, initiatives to
develop national action plans have commenced with the support
of the World Health Organisation’s Western Pacific Regional
Office. Fiji launched its national action plan in 2015, and, in the
absence of active surveillance programs, has focused on the
dissemination of messages about appropriate antibiotic use.

CHAPTER 16
AUTHORS: SOUTH AFRICA: ADRIAN BRINK, ASIA: CHAND WATTAL & REENA RAVEENDRAN, SOUTH AMERICA: ANAHI DRESER
STEWARDSHIP IN THE
RESOURCE LIMITED SETTINGS
- EXAMPLES OF GLOBAL
SUCCESS STORIES

THE AIM OF THIS CHAPTER IS TO:
LEARNING OUTCOMES
To assess the role of prescription auditing & focused On completion of this chapter, the participant should be able to:
group discussions in antimicrobial stewardship. • Reflect how non-specialised pharmacists can coordinate
interdisciplinary engagement
To ascertain the effect of antibiotic consumption and
development of antimicrobial resistance in a tertiary • Outline how to effect change utilizing a formal model of
care hospital. step-wise change management and quality improvement
principles
Understand how non-specialised pharmacists without
• Using such a model, outline the design, implementation and
Infectious Diseases expertise can contribute to
maintenance of a prospective pharmacist-driven audit and
stewardship initiatives within a hospital or within a
feedback stewardship intervention in a variety of
hospital network
geographical and socio-economic settings
Understand how to implement a pharmacist-driven • Outline the apparent skills beyond those of infectious
prospective audit and feedback model to initiate and diseases and microbiology that are critical in starting and
maintain AMS programs in single or multiple non- maintaining a sustainable AMS program, and as such the
academic urban and rural institutions: participants should be able to:
• Reducing excessive prescribing by targeting • Define the important determinants of a collaborative
basic antibiotic processes (“low-hanging fruit”) model to achieve breakthrough in improvement
• Improving time from antimicrobial prescription to • Define how effective behaviour change techniques (BCTs)
infusion (“Hang-time”) are used in the model, such as self-monitoring, feedback
combined with goal setting and action plans
• Improving adherence to peri-operative antibiotic
prophylaxis guidelines to enable a reduction in • Outline the methods to monitor and evaluate the impact of
surgical site infections regulating antibiotic sales.
• Reflect on the importance of managing the political sphere
To understand how regulatory intervention is relevant
during the process of introducing antibiotic sales regulation.
for the AMS goal of improving patient safety by curbing
self-medication practices and reducing antibiotic • Understand how to prepare an antibiogram for their hospital
consumption at the community level. as well as for the community
• Understand how to collect antibiotic consumption data
To understand the process of developing antibiotic sales
through prescription auditing.
regulation in resource limited settings, where problems
on access to antibiotics, and excess in their use coexist. • Understand how to carry out focus group discussions with
their clinical colleagues in different specialties.

CHAPTER 16 - STEWARDSHIP IN THE RESOURCE LIMITED SETTINGS - EXAMPLES OF GLOBAL SUCCESS STORIES
INTRODUCTION
Although developing and implementing a successful AMS
program is a challenge in any healthcare setting, there are
unique challenges to smaller and rural hospitals with limited
resources which may hamper the ability to implement ideal
sustainable AMS strategies (Figure 1). Thus, there is a need for
alternative stewardship models that use available organisational
infrastructure and resources. Furthermore, contextual aspects in
resource-limited settings also place a challenge to develop AMS
programmes at the community level. To illustrate, this chapter
describes the experiences of five countries with different AMS
approaches but with successful outcomes.
FIGURE 1
Barriers to implementation of AMS
SOUTH AFRICA PROCESS MEASURES INVOLVING “LOW-

HANGING FRUIT” FOR PHARMACIST AUDIT
GLOBAL SUCCESS STORY: DURING DEDICATED ANTIBIOTIC ROUNDS
ANTIMICROBIAL STEWARDSHIP MODEL (ALL PATIENTS ON ANTIBIOTICS)
TO REDUCE EXCESSIVE PRESCRIBING
The primary metric was overall reduction in consumption by
The aims of this model were to promote collaborative action
focusing initially on” low-hanging” fruit in reference to AMS. This
utilising existing resources and the concept of “low hanging
refers to selecting the most obtainable audit targets with limited
fruit”, across a diverse group of 47 urban and rural private SA
resources. In addition, such simple interventions as opposed
hospitals (Netcare Ltd), with regard to both implementation of an
to more complex strategies are ideal to initiate an initial AMS
AMS program, and to achieve a sustainable reduction in overall
program if stewardship has not started yet. The reasons are
antibiotic consumption. The reasons for utilizing pharmacists is
further elucidated in video 2
explained in following video:
THE REASONS FOR THE REASONS FOR

IMPLEMENTING AMS IN THIS CHOOSING “LOW-HANGING
WAY AND WHY PHARMACISTS AMS FRUIT” FOR PHARMACIST
WERE USED. AUDIT
VIDEO INTERVIEW WITH DR DENA VAN DEN VIDEO INTERVIEW WITH DR DENA VAN DEN
BERGH, QUALITY IMPROVEMENT DIRECTOR, BERGH, QUALITY IMPROVEMENT DIRECTOR,
NETCARE LTY (LTD) NETCARE LTY (LTD)
WATCH VIDEO WATCH VIDEO
Brink et al. Lancet Infect Dis 2016; 16: 1017–25

PROCESS MEASURES A DEFINITION
1 Cultures not done prior to Patients started on empiric antibiotics and no cultures performed within 48 hours prior to or
commencement of empiric on initiation of treatment.
antibiotics
2 More than 7-days of Prolonged duration of treatment included therapy which continued for between 8-14 days
antibiotic treatment (inclusive) i.e. antibiotic therapy exceeding the duration deemed longer than appropriate for
effective treatment of that particular agent or condition, according to local guidelines.
3 More than 14-days of Prolonged duration of treatment included therapy which continued beyond 14 days i.e.
antibiotic treatment antibiotic therapy which exceeds the duration deemed longer than appropriate for effective
treatment of that particular agent or condition, according to local guidelines.
4 More than 4 antibiotics at The unintentional overprescribing and concurrent systemic use of 4 or more antimicrobials
the same time in a given patient on the same calendar day for at least two consecutive days.
5 Concurrent “double” The intentional concurrent administration of two or more antibiotics with overlapping or
or redundant antibiotic duplicate spectra in terms of Gram-negative, Gram-positive and anaerobic cover, on the
coverage same calendar day for at least two consecutive days.
5.1 Redundant Gram-negative Defined as the concurrent administration of two or more of any of the following agents
coverage in or between groups: cephalosporins (cefuroxime, ceftriaxone, ceftazidime, cefotaxime,
cefepime); fluoroquinolones (ciprofloxacin, levofloxacin); penicillin/ β-lactamase-inhibitor
combinations (amoxicillin/clavulanate, piperacillin/tazobactam); aminoglycosides (amikacin,
gentamycin, tobramycin); carbapenems (meropenem, ertapenem, doripenem or imipenem)
and tigecycline.
5.2 Redundant Gram-positive Defined as the concurrent administration of two or more of any of the following agents in
coverage or between groups: β-lactams (amoxicillin, amoxicillin-clavulanate, cefazolin, cloxacillin),
tigecycline, clindamycin, linezolid and glycopeptides (vancomycin, teicoplanin).
5.3 Redundant anaerobe Defined as the concurrent administration of two or more of any of the following agents in or
coverage between groups: metronidazole, penicillin/ β-lactamase-inhibitor combinations (amoxicillin/
clavulanate, or piperacillin/tazobactam), carbapenems (meropenem, ertapenem, doripenem
or imipenem), moxifloxacin, clindamycin, cefoxitin, or tigecycline.
TABLE 1
Defining the process measures for audit. Reproduced with permission Lancet ID
A
For all of these audit measures, doctors were consulted by the pharmacist before any changes were effected
(face-to-face, verbal or mobile phone messages).
AMS “BREAKTHROUGH SERIES

COLLABORATIVE” MODEL FOR
IMPLEMENTATION AND
MONITORING PROCESS
The AMS model, a Netcare adaptation of the “Institute for
Healthcare Improvement (IHI) Model” (PDSA cycles) and the
“Breakthrough Series Collaborative” was implemented in
a step-wise manner (Figure 2).

FIGURE 2
Figure 2 Netcare AMS model for implementation
THE MODEL FOR IMPROVEMENT REQUIRES

The “Breakthrough Series Collaborative” requires adherence to
fundamental tenets (Video 3)
COLLABORATIVE PHARMACIST TEAMS TO
ASK THREE QUESTIONS
VIDEO INTERVIEW WITH DR DENA VAN DEN
BERGH, QUALITY IMPROVEMENT DIRECTOR,
NETCARE LTY (LTD)
WATCH VIDEO

THE IMPORTANCE OF COLLABORATIVE THE IMPORTANCE OF FEEDBACK TO

LEARNING SESSIONS AND STANDARDISED FACILITATE ADJUSTMENTS TO HOSPITAL
MEASUREMENT ACTION PLANS FOLLOWING SELF-
Initial training for the five interventions was provided through
MONITORING
face-to-face regional learning sessions with pharmacists as Improvements in the five interventions were measured by the
well as to pharmacy managers, clinicians, nurses and infection project manager via quality improvement run charts (Figure 4)
prevention practitioners (Learning session 1). In line with the and hospital feedback provided monthly via email and during
breakthrough series model, each pharmacist was then required learning cycles. A summary of the model is depicted in Figure 5.
to undertake an implementation process in their hospital
Netcare Group (n=47 hospitals) weekly run chart: Antibiotic
including collection of audit data on a standardised template
duration > 7 days
(.xls). Following Learning session 1, conference calls were held
every 6-8 weeks with pharmacists nationally, hosted by the QI
director and AMS project manager (Learning session 2 - ∞). In
between the learning sessions support was provided by the
project manager.
Aims of the joint learning cycles (sessions)
• Collaborative learning between hospitals

• Clarify requirements of AMS implementation
• Brainstorming of ideas to overcome obstacles to
implementation
• Sharing of success
• Evaluation of accuracy and consistency of data FIGURE 4
Example of a run chart for one of the audited measures (antibiotics
• Comparative feedback on progress and improvements
prescribed for > 7 days)
or otherwise
Aims of feedback by the project manager to the hospitals:
AIMS OF THE LEARNING • Provide monthly feedback to pharmacists and their managers,
specifically regarding:
CYCLES AND IMPORTANCE OF
• Improvements in compliance with the measures
STANDARISED MEASUREMENT (or otherwise)
VIDEO INTERVIEW WITH MS ANGELIKI • Improvements in antibiotic consumption data measured
in DDDs/100 bed days (or otherwise)
MESSINA, AMS PROJECT MANAGER,
• Individualized goals
NETCARE LTY (LTD)
• The pharmacists in turn provided verbal and/or written
feedback (1-3 monthly) to doctors, hospital management and
WATCH VIDEO AMS committee’s including IPPs of each hospital.
• Following goal setting and hospital self-monitoring, action
plans were adapted to:
At all participating sites data was collected weekly on a • Incorporate how much time pharmacists spent performing
standardised measurement tool (Figure 3) during pharmacist daily auditing activities
AMS ward rounds conducted initially in intensive care and • How many of the targeted interventions had been
high care units followed by audits in wards. Audits did not implemented?
occur for established extended treatment syndromes such
• What improvements had taken place?
as infective endocarditis and other deep-seated infections
(e.g. osteo-myeilitis. Mandatory monthly submission of audit • What the impact on individual hospital antibiotic
data using the measurement tool was sent via email to the consumption had been?
AMS project manager.

Denominator Numerator
Total number of patients where the
Total number of patients on antibiotics
particular “low-hanging-fruit” intervention
Week reviewed during dedicated stewardship % Compliance
was implemented with the doctor’s
rounds
permission
Week 1 17 13 76.5
Week 2 27 19 70.4
Week 3 19 15 78.9
Week 4 29 19 65.5
Week 5 36 19 52.8
Week 6 26 21 80.8
Week 7 20 15 75.0
Week 8 15 10 66.7
Week 9 10 10 100.0
Week 10 16 14 87.5
Week 11 20 19 95.0
Week 12 13 10 76.9
Week 13 10 7 70.0
Week 14 11 9 81.8
Week 15 23 19 82.6
Week 16 10 6 60.0
Week 17 19 14 73.7
Week 18 21 19 90.5
Week 19 32 24 75.0
Week 20 13 9 69.2
Week 21 13 8 61.5
Week 22 21 18 85.7
Week 23 21 20 95.2
Week 24 22 21 95.5
Week 25 17 14 82.4
Week 26 22 16 72.7
Week 27 25 17 68.0
Week 28 18 17 94.4
FIGURE 3
Example of a standardised measurement tool
DOWNLOAD DATA
COLLECTION TEMPLATE

FIGURE 5
Graphic summary pharmacist-driven audit and feedback model
IMPACT OF THE AMS MODEL

Fifty-three leaning cycles were held. For 104 weeks of
standardized measurement and feedback, 116 662 patients on
antibiotics were reviewed, with 7 934 interventions recorded for
the five designated examples of “low-hanging fruit”, indicating
that almost one in 15 prescriptions required pharmacist
intervention. 39% (3316) of 7934 pharmacist interventions
were for excessive duration. The model had a significant
impact on antibiotic consumption, with a lowering of 18.35 in
mean antibiotic DDD/100 bed days from 101.40 (95% CI 91.19
– 111.61) to 83.04 (95% CI 76.33 – 89.76) in the pre-and post-
implementation phases, respectively, representing an 18.1%
reduction in overall consumption (p < 0.001). (Figure 6)

DDD/100 bed days
Month/Year
FIGURE 6
Mean antibiotic consumption for three phases of the Netcare antimicrobial stewardship model (n=47 hospitals) (Oct 2009-September 2014)
To illustrate how this pharmacist-driven model can be used as

a stewardship strategy to target other interventions, you may
wish to watch the following slideshow: TOOLKIT RESOURCE
Slideshow lecture briefly outlining use of the same audit ARTICLES
and feedback ams model to improve antibiotic “hangtime”
ANTIBIOTIC “HANG-TIME”
and to improve compliance with a peri-operative antibiotic
Messina et al. Infect Dis Ther (2015) 4 (Suppl
prophylaxis guideline.
1):S5–S
PERIOPERATIVE ANTIBIOTIC PROPHYLAXIS

Brink et al. J Antimicrob Chemother 2017; 72:
VIEW SLIDE SET 1227–1234

INDIA
High burden of infection results in over and inappropriate use
of antimicrobials in low and middle-income countries in Asia.
There is no active AMSP program in most of their health care
facilities. Considering this it is imperative that a tool kit is made
which can be readily available as a web resource.
DEVELOPMENT OF DRUG RESISTANCE

There is a well-established association at the population level
between antibiotic consumption and antimicrobial resistance.
A 10-year (1999-2008) trend analysis of antimicrobial
consumption and development of resistance in non-fermenters,
in Sir Ganga Ram Hospital, established the association between
increase in consumption of carbapenems and the associated
development of resistance in A. baumanii. Another study on
10-year analysis of multi-drug resistant blood stream infections
caused by enterobacteriaceae also established the association
between resistance and consumption of carbapenem and
piperacillin/tazobatum in K. pneumoniae.

STORY 1: MAKING & UTILISATION OF AN

ANTIBIOGRAM: BUGS VS DRUGS
Understanding the epidemiology and emerging resistance trends
at an institutional level is essential for choosing appropriate
empiric therapy, monitoring resistance trends over time (within
an institution & across institutions), infection control activities &
resistance containment strategies.
But antimicrobial resistance is currently found almost as

frequently in the community as well. Since there was very
little data available on antimicrobial resistance in community
especially in developing countries, we tried to establish a new
methodology for surveillance of antimicrobial resistance in
low-resource setting in the community. This was a project in
collaboration with WHO and antimicrobial use was also being
monitored simultaneously during a period of 2004 to 2008.

STORY 2: PRESCRIPTION AUDITING AS A

CONCEPT AND INTERPRETATION
A study was done in our hospital which is a 675-bedded tertiary
care hospital in New Delhi, between August 2010 and June
2011, to evaluate if the feedback to clinicians of their own
antibiotic prescribing data result in any change in their antibiotic
prescribing habits. The antibiotic prescribing rates measured
as daily defined doses/100 bed days (DDD/100BD) on hospital
based prescribers. The high antibiotic prescribing units of the
hospital were divided into 2:
1. In the intervention arm, information on resistance rates and

antibiotic-prescribing patterns were provided to all doctors.
Comparison information with peer units within the specialty
(without disclosing the identity of the units) and the rest of
the hospital was also distributed.
2. In the control arm, only information on resistance rates was

provided every month.
The following achievements were noted:
1. The information gathered was useful to start locally

relevant interventions.
2. Established a methodology to study antimicrobial use

and resistance in communities in resource poor settings.
3. Involving several types of health-care facility at the

community level for data collection increased awareness
of the issue of growing resistance to antimicrobial therapy
and its relation to antimicrobial use.

In our study, providing doctors with information on how their

antibiotic-prescribing rates compared to those of their peers
showed no change in prescribing patterns, even among high
prescribers. It has been shown, in developed countries, that
prospective audit of antimicrobial use with direct interaction and
feedback to the prescriber can result in reduced inappropriate
use of antimicrobials. Such studies are seldom done in resource
poor settings. This study was the first from India on the
effectiveness of intervention program through feedback to the
physicians of their own prescription habits in a hospital setting.
The result of this study was suggestive that passive intervention
only did not elicit desirable behavioural change in the physicians
whereas the possibility of direct interaction with the prescribers
to reduce antimicrobial consumption may be more effective at
least in our setting.
Any significant behaviour changes in the two groups

were assessed by comparing baseline (pre-intervention) TOOLKIT RESOURCE
antibiotic-prescribing rates with post-intervention antibiotic- SITE LINK
prescribing rates.
http://www.cochrane.org/CD000259/EPOC_audit-
and-feedback-effects-on-professional-practice-and-
patient-outcomes
STORY 3: FOCUS GROUP DISCUSSIONS

With the knowledge we gained from the previous study,
we moved on to our next venture, focus group discussions
(FGDs). Persuasive intervention in the form of monthly
prescription auditing and feedback on antimicrobial prescribing,
dissemination of educational resources and reminders were
continued, but in addition, FGDs were performed. The aim of
this study was to evaluate the impact of FGD as an adjunct
intervention to the feedback strategy on antibiotic prescribing
rates on hospital based prescribers before and after the FGD.
The doctors of 45 surgical units of the hospital were included
in the study which extended from June 2013 to August 2015.
Every month FGD was conducted with one specialty to cover
all specialties included in the study on turnkey basis. Method,
significance of measuring antibiotic consumption, the possible
reasons for high antibiotic prescription of a particular unit and
adherence to the antibiotic policy were discussed.

to 31.42% at 6 months of intervention. Although previous

intervention studies from the west have demonstrated successful
strategies for altering prescribers’ behaviour, most have focused
on discouraging use of specific drugs rather than reducing
overall antibiotic prescriptions. The study throws up
the challenge at the sustainability of the intervention as the
effects did not persist for more than 3 months irrespective of
the surgical specialty.

TOOLKIT RESOURCE
SITE LINK
http://www.health.org.uk/publication/path-
sustainability
OTHER CONTRIBUTORY FACTORS

We organised ASPs and devoted time on education process
and expected significant changes in prescribing habits. But,
our experience in the field suggest that there are certain
other factors like infection control activity play a significant
role in amplifying & disseminating bacterial resistance which
consequently influences the prescribing habits. The increasing
number of invasive measures and interventions as well as
existing poor hygiene standards play a significant role in
determining bacterial resistance in LMICs. The best approach
in settings with a high prevalence of MDR pathogens probably
involves hand hygiene plus careful assessment of the institutions
At the end, consensus recommendations were made with circumstances and application of more aggressive measures
the aim to reduce their antibiotic prescription rate. To assess such as patient isolation, staff cohorting, and active surveillance
the impact and sustainability of FGD, pre-intervention antibiotic cultures.
consumption data was compared with the prospective or
post intervention data of the respective units 3 and 6 months’ In conclusion, antimicrobial resistance has reached dangerous
post FGD. levels & prescribing practices have to change in order to combat
this problem. Newer antibiotics may not offer a solution on their
Overall antibiotic prescription reduced from 190.68 DDD/100BDs own as they are likely to be expensive and unaffordable in the
to 185.88 DDD/100 BDs (-2.5%) and 187.14 DDD/100 BDs (-1.88%) developing world. More importantly, the newer drugs will also
in 3 and 6 months’ period post-intervention, respectively. eventually lose their potency. We will continue the cycle unless
Increase in the use of penicillin, 2nd generation cephalosporins we change our approach towards antibiotic usage. Adherence
and clindamycin was associated with decrease in use of 3rd & to evidence based practice is essential which includes
4th generation cephalosporins, β lactam inhibitors, quinolones, improved diagnostic services & availability of antimicrobial
macrolides, aminoglycosides, carbapenems, glycopeptides, resistance surveillance data. Educating public in correct use of
linezolid, colistin and tigecycline. antimicrobials could go a long way towards curbing resistance.
This study highlighted two important facts. First, the meagre In addition to the above measures, to reduce antimicrobial
reduction (-1.88%) in antibiotic consumption post intervention resistance and consequent antimicrobial consumption in
and second, poor sustainability of the impact shown by hospitals, it is necessary to have a good ASP combined with
initial (post 3 months of intervention) reduction of antibiotic optimal adherence to infection control measures. It is a challenge
prescription seen in 42.8% of the units which further reduced to bring this change in developing countries.

SOUTH AMERICA This situation was especially sensitive in Mexico, where up to

40% of all antibiotics were obtained without medical prescription
STORY 1: THE PROBLEMS: INAPPROPRIATE in private pharmacies and where they were sold by undertrained
ANTIBIOTIC USE AND ANTIBIOTIC clerks –not dispensed by pharmacists. This country had had the
RESISTANCE IN LATIN AMERICAN highest level of consumption in the region, although it showed
COUNTRIES a decreasing trend. However, consumption of quinolones and
During the late 1990’s, leading Latin American infectious disease new macrolides (such as azithromycin) rose sharply, as in other
specialists warned: “The giant is awakening”, urging to raise countries in the region (Figure 7).
awareness and act upon the increasing bacterial resistance
in the region. The Pan American Conference on Antimicrobial STORY 2: THE PROCESS AND IMPACT
Resistance, organised by PAHO and the Pan American Infectious OF INTRODUCING REGULATIONS FOR
Disease Association (API) in 1998, called for action to identify ANTIBIOTIC SALES IN CHILE, BRAZIL
priority problems and required interventions. Since then, a AND MEXICO
series of studies were undertaken aiming to: a) assess antibiotic
consumption levels, using sales data converted into defined Following concern with the problems of bacterial resistance,
daily dose per 1000 inhabitants per day (DDD/TID); b) identify high levels of consumption and self-medication with antibiotics
antibiotic prescription, dispensing and consumption patterns in Latin America, several countries have introduced regulatory
through household, pharmacies and healthcare setting surveys. measures to restrict antibiotic sales, either at the national or
sub-national level. The experiences of Chile, Mexico and Brazil
These studies identified the problem of inappropriate antibiotic offer a good example of the challenges and opportunities for
use in the region as twofold: 1) unjustified antibiotic prescription introducing this regulation, as well as to understand its impact.
by health care professionals, especially with broad spectrum
antibiotics; and 2) self-medication with antibiotics. With regard Chile
to this second problem, a revision of pharmacy legislation Chile regulated antibiotic sales only with medical prescription
in Latin American countries conducted by PAHO concluded in 1999. Governmental attention was facilitated by available
that antibiotics were actually considered as prescription-only indicators on antibiotic consumption and antibiotic resistance.
medicines by all national legislations. However, law was not Infectious-disease specialists acted as policy entrepreneurs
enforced due contextual factors including: insufficient health calling the attention of health officials to these problems and
care coverage and access to public services and medicines; to PAHO recommendations. The feasibility of the regulation of
within governmental institutions, scarce awareness about the antibiotic sales was further facilitated by a positive previous
problem of antibiotic misuse, and regulatory weaknesses, which experience in regulating benzodiazepine sales. The introduction
led to scarce inspection and sanctions to pharmacies; and within of the regulation was accompanied by extensive media
the community, strong cultural beliefs with regard to antibiotics coverage, public information campaign and involvement of
use. These factors led to a high demand for antibiotics and an community pharmacies.
ample offer in private pharmacies.
FIGURE 7
Trends in a) Overall antibiotic utilization, and b) Quinolone utilization in eight Latin American countries, 1997-2007. Source: Wirtz VJ, Dreser A and
Gonzales R (2010). Trends in antibiotic utilization in eight Latin American countries, 1997–2007. Rev Panam Salud Pública 27: 219–225

An initial 30% overall decrease on antibiotic consumption Brazil

was attained, which affected mainly those antibiotics that The Brazilian National Health Surveillance Agency (ANVISA)
were previously sold without prescription (penicillins and had been discussing the need to improve the control of
cotrimoxazole). The initial dramatic success of this regulation antibiotic sales since 2009. However, it was the spread of the
was short-lived: as campaigns were not sustained, three multi-resistant KPC bacteria and related deaths during 2010 –
years later antibiotic consumption levels rose again; however, followed widely by the media– which speeded up the regulation
consumption remained below the pre-intervention level process. The regulation was implemented since November
(Figure 8). 2010, establishing that antibiotics were to be sold only with
prescription, which was to be retained in pharmacies. The
Slide presentation:
resolution was supported mainly by medical groups, but faced
Impact of regulatory measures on antibiotic sales in Chile
the opposition of pharmacy and commerce associations. Arguing
the social impact of the regulation (e.g. insufficient infrastructure
of public medical services, scarce access to medical care in
VIEW SLIDE SET rural areas, and the risk of triggering a parallel black market of
antibiotics) these associations sought to withdraw the resolution.
Nevertheless, the resolution was implemented. An interrupted
time series analysis using the DDD/TID unit concluded that,
two years after the regulation, antibiotic consumption in the
private sector decreased by nearly 24% (Figure 9). Aiming to
overcome problems with pharmacies’ compliance, a stricter
regulation was introduced in April 2013, incorporating antibiotics
into the ANVISA national system for management of controlled
substances.
Mexico
The problems of antibiotic use had remained low in the health
policy agenda of Mexico, where attaining access to medicines
has been top priority. However, in 2009, in the midst of the
influenza A H1N1 pandemic, self-medication with antibiotics
was associated with delayed medical care and high influenza
mortality in the country. This created an unprecedented public
debate. Infectious disease specialists, public health and
FIGURE 8 veterinary experts saw this as open window of opportunity
Impact of antibiotic sales regulation in Chile. Source: Herrera-Patiño to propose to the government priority actions to improve
J, Santa-Ana-Tellez Y, Dreser A, Gonzalez R, Wirtz VJ. Consumption of antimicrobial use and mitigate resistance. The Ministry of
antibiotics before and after sales regulations in Chile, Colombia and
Health enacted a decree effective as of August 2010, which
Venezuela. In: http://slideplayer.com/slide/8478401/
enforced the regulation of antibiotic sales only with medical
prescription; additionally it required prescriptions to be retained
Slide presentation: and registered in pharmacies, and imposed high penalties
Consumption of antibiotics before and after sales regulations for non-compliance. Pharmacy associations opposed to the
in Chile, Colombia and Venezuela regulation, arguing economic losses and logistical difficulties for
the pharmacies, as well as the negative health and economic
effects on poor populations with scarce access to healthcare.
Bigger pharmacy chains developed a different strategy, by
VIEW SLIDE SET opening medical clinics adjacent to pharmacies. Between 2010
and 2013, the number of these pharmacy clinics, offering cheap
or even free consultation (and antibiotic prescriptions), tripled in
the country –buffering the impact of the regulation.

Slide presentation:
Regulation of antibiotic sales in Mexico: process and impact
TOOLKIT RESOURCE
ARTICLES
VIEW SLIDE SET Bavestrello, L. and Cabello, Á. (2011). Community
antibiotic consumption in Chile, 2000-2008. Rev
Chil Infect, 28(2), 107-112.
An interrupted time series analysis using the DDD/TID unit
to assess the impact of the regulation concluded that there Dreser, A., Vázquez-Vélez, E., Treviño, S. and Wirtz,
was an overall 12% decrease (around 1 DDD/TID) on antibiotic V.J. (2012). Regulation of antibiotic sales in Mexico:
consumption, largely because penicillins; no shift toward use of an analysis of printed media coverage and
other classes of antibiotics, such as quinolones, was observed. stakeholder participation. BMC Public Health,
A clear reduction on the seasonal variation on amoxicillin 12, 1051.
(34%) and ampicillin (93%) consumption (which were best-
seller medicines in the country), as well as an increase in the Santa-Ana-Tellez, Y., Mantel-Teeuwisse, A. K.,
use of some symptomatic medicines (as substitute products) Leufkens, H. G. M., & Wirtz, V. J. (2015). Seasonal
was also documented. Another study concluded that, after the Variation in Penicillin Use in Mexico and Brazil:
regulation, there was no increment in hospital admissions related Analysis of the Impact of Over-the-Counter
to bacterial infections, a feared side-effect of the intervention. Restrictions. Antimicrobial Agents and
This body of evidence points to the success of the regulatory Chemotherapy, 59(1), 105–110.
intervention on curbing unnecessary antibiotic use by self-
medication in the country. Monitoring and improving medical
prescription, especially on the emerging pharmacy clinics,
remain an important challenge.
FIGURE 9
Trends in antibiotic consumption for Brazil and Mexico (2007–2012), and impact of the 2010 regulation on antibiotic sales. Source: Santa-Ana-Tellez
Y, Mantel-Teeuwisse AK, Dreser A, Leufkens HGM, Wirtz VJ (2013) Impact of Over-the-Counter Restrictions on Antibiotic Consumption in Brazil and
Mexico” PLOS ONE, 2013; 8; 10 ; e75550-e75550)

CONCLUSIONS Biblography:
Howard P, Pulcini C, Levy Hara G, et al. An international cross-
Taken together, the cases of these Latin American countries
sectional survey of antimicrobial stewardship programmes in
show that regulating antibiotic sales can be very politically
hospitals. J Antimicrob Chemother 2015; 70: 1245–255.
sensitive issue in resource limited settings, because insufficient
access to health care, and because economic interests are Huttner B, Harbarth S, Nathwani D, and on behalf of the ESCMID
affected. However, media attention, together with the efforts Study Group for Antibiotic Policies (ESGAP). Success stories of
of concerned researchers, public health and infectious disease implementation of antimicrobial stewardship: a narrative review.
specialists can draw political will. Using a standard methodology, Clin Microbiol Infect 2014; 20: 954–62
it was possible to prove that these regulatory interventions were The Breakthrough Series: IHI’s Collaborative Model for Achieving
successful in curbing self-medication practices and reducing Breakthrough Improvement. IHI Innovation Series white paper.
antibiotic consumption in the community. The remaining Boston: Institute for Healthcare Improvement; 2003. (Available
challenge for the region in years to come is to improve the on www.IHI.org).
quality of medical antibiotic prescription, both in hospital and Cosgrove SE, Hermsen ED, Rybak MJ, et al. Guidance for the
ambulatory care. A number of interesting AMS programmes are knowledge and skills required for antimicrobial stewardship
now being developed in Latin American hospitals --particularly leaders. Infection Control and Hospital Epidemiology 2014; 35:
in Colombia. The processes and impact related to their 1444-51
implementation have to be well documented in order to gain
Charani E, Holmes AH. Antimicrobial stewardship programmes:
valuable lessons for the region.
the need for wider engagement. BMJ Qual Saf 2013; 22: 885–87
Hamilton KW, Fishman NO. Antimicrobial stewardship
interventions. thinking inside and outside the box. Infect Dis Clin
North Am 2014; 28: 301–13
Langley GL, Moen R, Nolan KM, Nolan TW, Norman CL, Provost
LP. The Improvement Guide: A Practical Approach to Enhancing
Organizational Performance (2nd edition). San Francisco: Jossey-
Bass Publishers; 2009. P89-108
Perla R, Provost L, Murray S. The run chart: a simple analytical
tool for learning from variation in healthcare processes. BMJ
Qual Saf 2011; 20: 46-51.
Goel N, Wattal C, OberoiJK, Raveendran R, Datta S, Prasad KJ.
Trend analysis of antimicrobial consumption and development of
resistance in non-fermenters in a tertiary care hospital in Delhi,
India. J AntimicrobChemother 2011;66(7):1625-1630.
Datta S, Wattal C, Goel N, Oberoi JK, Raveendran R, Prasad KJ.
A ten years trend analysis of multi-drug resistant blood stream
infections caused by E.coli and K.pneumoniae in a tertiary case
hospital. Ind J Med Res. 2012;135:907-12.
Wattal C, Sharma A, Raveendran R, Bhandari SK, Khanna S.
In Community-Based Surveillance of Antimicrobial Use and
Resistance in Resource Constrained Settings. Report on five pilot
projects. Editors: Holloway KA, Mathai E, Sorensen T, Gray A.
World Health Organization. 2009; WHO/EMP/MAR/2009.
Wattal C, Raveendran R, Kotwani, A, Sharma A, Bhandari SK,
Sorensen TL, Holloway K. Establishing a new methodology for
monitoring of antimicrobial resistance and use in the community
in a resource poor setting. Journal of Applied Therapeutic
research, 2009;7(2): 37-45

C Wattal, N. Goel, S. Khanna, SP Byotra, R Laxminarayan,

A Easton. Impact of informational feedback to clinicians on
antibiotic-prescribing rates in a tertiary care hospital in Delhi.
Indian Journal of Medical Microbiology. 2015;33(2):255-259.
Levy G, Savio E, Castro J, Calmaggi A, Arzac M, Clara L. Study of
antibiotic use in Argentina and Uruguay. In: Salvatierra-González
R, Benguigui Y, eds. Antimicrobial resistance in the Americas:
magnitude and containment of the problem. Washington, DC:
PAHO; 2000. Pp. 235–9.
Wirtz, V.J., Dreser, A. and Gonzales, R. (2010). Trends in antibiotic
utilization in eight Latin American countries, 1997–2007.
Panamerican Health Organization J, 27(3), 219–225
Bavestrello, L. and Cabello, Á. (2011). Community antibiotic
consumption in Chile, 2000-2008. Rev Chil Infect, 28(2), 107-112.
Dreser, A., Vázquez-Vélez, E., Treviño, S. and Wirtz, V.J. (2012).
Regulation of antibiotic sales in Mexico: an analysis of printed
media coverage and stakeholder participation. BMC Public
Health, 12, 1051.
Wirtz, V.J., Herrera-Patino, J.J., Santa-Ana-Tellez, Y., Dreser, A.,
Elseviers, M. and Vander Stichele, R.H. (2013). Analysing policy
interventions to prohibit over-the-counter antibiotic sales in four
Latin American countries. Tropical Medicine and International
Health, 18(6), 665–673.
Santa-Ana-Tellez, Y., Mantel-Teeuwisse, A.K., Dreser, A., Leufkens,
H.G.M. and Wirtz, V.J. (2013). Impact of Over-the-Counter
Restrictions on Antibiotic Consumption in Brazil and Mexico. PLoS
ONE, 8(10), e75550.
Zaidi, M.B., Dreser, A. and Figueroa, I.M. (2014). A collaborative
initiative for the containment of antimicrobial resistance in
Mexico. Zoonoses and Public Health, 61(2), 1-6.
Santa-Ana-Tellez, Y., Mantel-Teeuwisse, A. K., Leufkens, H. G.
M., & Wirtz, V. J. (2015). Seasonal Variation in Penicillin Use in
Mexico and Brazil: Analysis of the Impact of Over-the-Counter
Restrictions. Antimicrobial Agents and Chemotherapy, 59(1),
105–110.
Rubli, A. (2015). Supply Regulations in the Market for
Medicines: Evidence from an Antibiotics Law in Mexico.
Working paper. Available at: http://lacer.lacea.org/bitstream/
handle/123456789/53118/lacea2015_market_medicines_mexico.
pdf?sequence=1

CHAPTER 17
AUTHOR: AOIFE FLEMING
STEWARDSHIP IN LONG
TERM CARE FACILITIES
LEARNING OUTCOMES
CHAPTER IS TO:
• Explain the unique factors impacting on AMR and AMS in LTCF
Outline the factors impacting • To understand the factors influencing the prescribing of antimicrobials in LTCF
on antimicrobial prescribing
• Identify and communicate the core goals of a LTCF AMS strategy
in Long Term Care Facilities
(LCTFs). • Reflect on their own practice and how to introduce AMS in LTCF
Describe the prevalence of

infection, antimicrobial LONG TERM CARE FACILITY SETTING FACTORS
prescribing and antimicrobial
Antimicrobial stewardship is vitally important in Long term care facilities (LTCFs). Over
resistance in LTCFs.
any given year, up to 70% of LTCF residents are prescribed an antimicrobial with studies
Describe the impact of suggesting that a large proportion of these prescriptions are inappropriate. Point
antimicrobial stewardship in prevalence studies have indicated that between 3% and 15% of LTCF residents are
this setting. prescribed antimicrobials at any given time. The CDC factsheet below outlines the scale of
antimicrobial prescribing in the United States of America.
THIS CHAPTER WILL

ALSO OUTLINE:
Strategies to combat AMR
in LTCFs.
Outline case scenarios and

examples of how to
implement AMS initiatives
at a local level.

CHAPTER 17 - STEWARDSHIP IN LONG TERM CARE FACILITIES
Risk factors for Healthcare associated Infections (HCAIs) in

LTCFs:
• co-morbidities, age related immune decline
• shared facilities (communal areas, toileting facilities,

bedrooms) and minimal isolation facilities for residents
with infections
• invasive medical devices e.g. urinary and vascular catheters,

gastrostomy tubes
• wound management
A meta-synthesis of studies investigating the factors influencing

antimicrobial prescribing in LTCF developed the conceptual
model as outlined in Figure 1.
VIEW DOCUMENT
CURRENT INFLUENCING LTCF AMS AMS STRATEGIES

FACTORS REQUIRED
LTCF context: lack of resources Customised to LTCF setting Continuous antimicrobial
(doctors, diagnostic equipment) prescription surveillance
Consider all relevant information
Social Factors: central role of nurse, Outcomes:
Address local barriers & facilitators
influence of family
- antibiotic prescribing rates
Knowledge & practice: Variable
- adherence to prescribing guidelines
knowledge of diagnosis & prescribing
guidelines - feedback from healthcare
professionals
Variable prescribing practice
between doctors LTCF Antimicrobial resistance data
FIGURE 1

The challenges of diagnosing and managing HCAIs

are compounded by the following;
ANTIMICROBIAL PRESCRIBING PRACTICES

TOOLKIT RESOURCE Antimicrobials are most frequently prescribed in LTCFs for
Urinary tract infections (UTIs), Respiratory tract infections (RTIs)
ARTICLES and Skin and Soft tissue infections.
Crnich C et al. Optimizing antibiotic stewardship There is significant variability in antimicrobial prescribing
in nursing homes: a narrative review and practices between LTCFs, as seen in large point prevalence
recommendations for improvement. Drugs Aging studies.
2015;32:699-716
Antimicrobial prescribing in LTCFs is variable between and within
LTCFs due to the following factors:
Dyar O.J et al. Strategies and challenges of
antimicrobial stewardship in long-term care • Medical care delivered in different structures e.g. one
facilities. Clinical Microbiology and Infection medical group practice, one general practitioner, several
2015;21:10-19 general practitioners from different practices or doctors
from adjunctive hospital/secondary care settings, on-call
doctor cover
• Not all LTCFs have doctor visits on a daily basis and access
to Infectious Diseases Consultants or specialist ID/
Antimicrobial Pharmacists is limited
• Doctors reliant on nursing staff to assess and communicate

information – frequent telephone ordering of antimicrobial
prescriptions without patient bedside consultation

Qualitative research investigating the factors influencing

antimicrobial prescribing in LTCFs has found that drivers of
antimicrobial prescribing in this setting are listed in the VIEW PAPER
following figure:
CONTEXT SOCIAL PRESSURE LACK OF

• Frail population • Residents' families
BEHAVIOURAL
- fear of consequences
REGULATION
• LTCF staff
of not prescribing • Lack of audit &
• Residents themselves
• High infection risk - feedback
age, co-morbidity, • Few AMS teams
changes in immune
response
• Lack of on-site
diagnostics & doctors
• Residents with
cognitive impairment
IMPACT OF ANTIMICROBIAL RESISTANCE often leads to infection.
There is a lack of local antimicrobial resistance data available to The risk of colonisation is driven higher by the following factors:
guide prudent prescribing in the LTCF setting. • recent antimicrobial use (within the last 4 months)
Subsequently, the rate of multidrug resistant organism (MDRO) • high resident dependency levels
infections in LTCFs is not well recorded.
• urinary or vascular catheters,
A study evaluating Centers for Medicaid and Medicare Services
Long Term Care Minimum Data Set (MDS) found a rate of MDRO • ulcers/wounds
infections of 4.2% among nursing home residents across the • urinary or faecal incontinence
USA (range 1.9% to 11.4% in individual states).
Risk factors for colonisation with Clostridium difficile in LTCFs
LTCF residents are commonly colonised by bacteria, which include:
makes the interpretation of microbiology samples complicated,
• previous history of C.difficile infection
with colonisation often judged as infection when the reports are
read. This can lead to unnecessary antimicrobial prescribing. • antimicrobial use with the last 3 months
Colonisation with MDROs is common – especially with Methicillin • recent hospitalisation.

Resistant Staphylococcus aureus (MRSA). Studies have found
LTCFs have been termed “reservoirs” for MDROs and C.difficile.
colonisation rates up to 50% in LTCFs, much higher than that
Case clusters of MDRO or C.difficile outbreaks in LTCFs in
5-10% among hospitalised patients.
regional LTCFs and acute hospitals have been published. The
The prevalence of Vancomycin Resistant Enterococci (VRE) close proximity of residents in either shared bedrooms or
ranges from 4-16% and is on the increase, as is the prevalence communal areas (bathrooms, dining etc.) contributes to the
of colonisation with Extended Spectrum beta-lactamase (ESBL) horizontal transmission of pathogens in LTCFs.
and Carbapenem Resistant Enterococci (CRE). These are areas
Evidence supports that there is a higher rate of AMR in the
of concern as the eradication of colonisation can be difficult and
LTCF population.

Hand Hygiene

TOOLKIT RESOURCE
Isolation procedures
SITE LINK Environment
Inter-institution resident
& Staff level
Fleming A et al. Eur J Public Health. 2017 Apr transfer
1;27(2):307-312. doi: 10.1093/eurpub/ckw138.
Antimicrobial susceptibility of long term care facility Ongoing surveillance/Audit
and general practice urine samples in patients 65 IPC
years and older: an observational study. Policies &
procedures
Examining the relationship between multidrug- Outbreak management e.g.
Influenza, C.difficile, MRSA
resistant organism acquisition and exposure to
antimicrobials in long-term care populations: a
Resident Catheter care
review. Michele L. Shaffer, PhDa, b, , , Erika M.C.
level
D'Agata, MD, MPHc, Daniel Habtemariam, BAd,
Susan L. Mitchell, MD, MPHc, d Annals of
Management of AMR cases
Epidemiology Volume 26, Issue 11, November 2016,
Pages 810–815
The importance of robust infection prevention and control for testing to the local microbiology laboratory as she suspects
systems in LTCF cannot be highlighted enough. As already influenza. The family are not happy about this and request that
mentioned, the transmission of pathogens, which could be the doctor prescribes co-amoxiclav.
potentially resistant, is a contributing factor to the development
What should the doctor do next?
of infectious outbreaks such as influenza. LTCF should follow
• The doctor should take time to discuss with the family and
national/regional protocols on IPC in practice.
the nurse that the presenting signs and symptoms are
Guidance on IPC is available on the CDC webpage: suggestive of influenza and not a COPD exacerbation.
He should outline that COPD has increased Mr Henry’s risk
of influenza and that there have been cases in the locality
in recent days.
VISIT SITE
• The doctor should examine the patient and ensure that there
is no secondary bacterial infection in the respiratory system
(check for consolidation, check breathing, type of cough,
The main features of an IPC policy and practice initiative in CURB score);
LTCFs should include the above Figure.
Case Scenario:
Mr Henry is a resident of Forest Glen nursing home and is VISIT SITE
79 years of age. He has a history of COPD, hypertension and
atrial fibrillation. The doctor is called to review the patient as
he is unwell and his family have become concerned and do
• Mr Henry has presented with uncomplicated Influenza
not want him to be transferred to the nearby acute hospital.
(no signs of lower RTI or CNS involvement or significant
Mr Henry routinely takes rampril, atorvastatin, tiotropium inhaler,
exacerbation of his COPD); therefore no hospital admission
fluticasone/salmeterol inhaler and salbutamol nebules prn.
is required at this point. However, the family should be made
There is no x-ray machine in the LTCF and the family ask the
aware that this situation could change and if transfer is
doctor to prescribe an antimicrobial co-amoxiclav which Mr
needed over the coming days they should be prepared for
Henry responded to 4 weeks ago. However, on review of the
this in Mr Henry’s best interests.
resident (fever >38oC, chills, sweating, headache, sore throat,
extreme fatigue) the doctor takes a throat swab and sends it

• An anti-viral agent such as Oseltamivir 75mg bd po should was 4.4% (n = 3,367 of 77,264) and this ranged from 1.0% in
be started as soon as possible without waiting for laboratory Hungary to 12.2% in Greece. Antimicrobials were most frequently
confirmation. (Note that Mr Henry does not have renal prescribed for the treatment of infection (72.8%), with RTIs
impairment, dose adjustment may be needed depending on (39.0%), UTIs (35.1%) and skin/wound infections (16.0%) being
the degree of renal impairment). the most commonly treated infections.
• A risk assessment should be conducted, as well as contacting The 2016 Irish national report has been published and included
the local public health office to notify them of the infection, data from 10,044 residents in 224 Irish LTCFs.
anti-viral chemoprophylaxis should be prescribed to other
residents at risk as per local guidance.
• Influenza vaccination status of all residents and staff should VIEW REPORT
be recorded, and non-vaccinated cases should be contacted
for vaccination. Remember it takes two weeks for the vaccine
to take effect.
The national report provides detailed information on the types
• Close the LTCF to visitors to reduce the spread of Influenza of LTCFs included and the prevalence of HAIs and enables
around the LTCF and into the community. countries to benchmark their performance against the European
average. Of particular interest from an AMS perspective is the
SURVEILLANCE OF HEALTHCARE detail on antimicrobial prescribing; the national crude prevalence
ACQUIRED INFECTIONS AND in Ireland in 2016 was 9.8% compared to the European average
ANTIMICROBIAL PRESCRIBING in 2013 of 4.4%. The indications for antimicrobial prescriptions
are well detailed. Also, due to Irelands participation in HALT
Several initiatives have been implemented over recent years
since 2010, the Irish HALT Steering Group have identified
to record, by means of point prevalence studies (PPS), the
a number of key priorities for implementation which will be
prevalence of HCAI and antimicrobial prescribing at a given point
discussed further later on the Chapter.
in time in LTCFs.
In Europe the European Centre for Disease Prevention and

Control (ECDC) has conducted a Point Prevalence Survey of
Healthcare-Associated Infections and Antimicrobial use in Long- A challenge for conducting AMS in LTCFs is that, compared to
Term Care Facilities (HALT) has been conducted in 2010, 2013 acute care settings, many of the key stakeholders to drive this
and 2016. agenda are based off site (e.g. medical physicians, pharmacists,
specialist public health/infection prevention & control nurses).
LTCFs have minimal in-house diagnostic facilities and the
turnaround time for microbiological and blood sample results can
VIEW PPS ARTICLE be several days.
In order to support LTCF to implement AMS initiatives the CDC

has published a very useful resource and more information is
The objectives of this PPS are to facilitate ECDC surveillance of available here;
Healthcare-associated Infections (HAIs) and antimicrobial use in
LTCFs. The most recent HALT study European level report has
not been published yet. The 2013 HALT report is available here:
WATCH VIDEO
VIEW REPORT
This report included 1181 LTCFs (77,264 residents) in 19 countries.

WATCH VIDEO
Data were collected on a single day and preparation involved
training LTCF staff to collect and submit the data. The crude
prevalence of residents receiving at least one antimicrobial

Key areas to focus on for LTCF AMS: It is important to consider that AMS initiatives in LTCFs require
tailored approaches suitable for the local context and supportive
ANTIMICROBIAL URINARY DIPSTICK organisational commitment.
PRESCRIBING • Reduce inappropriate
A pilot cluster randomised controlled in the United Kingdom
• follow local/national testing
evaluated the implementation of a paper-form in LTCFs that
guidelines • Correct interpretation &
follow up with urine required documentation of antimicrobial prescribing practices.
choose correct
antimicrobial for sample testing to The form required the recording of clinical signs & symptoms,
indication, correct dose confirm presence and/or physician evaluation, indication for the antimicrobial, appropriate
& frequency, follow up susceptibility diagnostic evaluation, clinical re-evaluation, and review of
on microbiolgy diagnostic tests within 48-72 hours, and duration of treatment.
investigations, The 12 week pilot study showed a significant decrease in
review duration
antimicrobial use of 4.9% in the intervention group (p=0.02)
compared with baseline, and a significant increase of 5.1% in the
URINARY CATHETERS IPC control group (p=0.04).
• reduce inappropriate • Reduce colonisation and
antimicrobial prescribing infection risk

for asymptomatic
bacteriuria
• focus on MDRO,
Influenza, C.difficile TOOLKIT RESOURCE
SITE LINK
http://www.leedscommunityhealthcare.nhs.uk/ ncbi.nlm.nih.gov
seecmsfile/?id=2322
Donlon et al Ireland Van Schooneveld et al.

ESAC Europe n = 260 HALT Europe n = 117
n = 69 Nebraska USA n = 37
Antimicrobial
8% 16% 16% 36%
stewardship committee
Therapeutic formulary 16% 57% 23% 19%
Antimicrobial guidelines 50% 45% 28% 27%
Data about antimicrobial
- 33% 16% 81%
consumption
Data about local
antimicrobial resistance 9% 17% 12% 76%
profiles
Regular training
of prescribers on 16% 22% 7% 8%
antimicrobial use
Individual antimicrobial
- 27% 10% 11%
prescribing profiles
Pharmacist advice on
- 19% 36% -
antimicrobial use
Regular audits assessing
- - - 81%
antimicrobial use
TABLE
Cross-sectional surveys of antimicrobial stewardship programmes in long-term care facilities.
Ref. Dyar et al Clinical Microbiology and Infection 2015;21:10-19.

An important development in the United States has been the Public Health England has published the following quick
Centers for Medicare and Medicaid requirement for all LTCF to reference guide with specific points on diagnosis for patients
have an antibiotic stewardship program by November 28 2017. >65 years:
VIEW ARTICLE VIEW GUIDELINE DOCUMENT
In order to support LTCF in the implementation of an antibiotic In Ireland, the following guidance for the diagnosis and
stewardship policy a comprehensive template was published by management of UTI in LTCF residents >65 years has been
Jump et al. available with several years:
VIEW TEMPLATE VIEW GUIDELINE DOCUMENT
FOCUS ON UTI AND CAUTI IN LTCF VIEW INFORMATION FOR

LTCF residents are at increased risk of antimicrobial prescribing CARE HOMES ARTICLE
for UTI and CAUTI (Catheter associated UTI). Some initial clinical
presentations may warrant an antimicrobial prescription – but
many do not. In order to improve the diagnosis of UTI in this The importance of tailoring antimicrobial prescriptions cannot
setting a structured and evidence based approach should be be highlighted enough and the Start Smart then Focus
followed. Many public health organisations have introduced at campaign should be adopted and adhered to in LTCFs should
local and/or national level guidance to improve the diagnosis and an antimicrobial be prescribed. This initiative was developed
treatment of UTI. It is important to note that the most relevant in the United Kingdom and has since been used widespread.
guidance to a LTCF is that which has been based on AMR data See Figure on the next page for the Irish Start Smart then Focus
and evidence from that region. Antibiotic Bundle for hospitals, the principles of which should
guide LTCF antimicrobial prescribing also.
Key points which are present across the guidelines are:
• Take care when interpreting urine dip sticks as false positive

results are often given due to the presence of asymptomatic
bacteriuria, especially in residents with a catheter
• A positive dipstick result in an asymptomatic patient is not

indicative of a UTI and should not be treated
• If a patient is treated empirically with antimicrobials, a urine

sample should be sent for microbiological investigation
before the antimicrobial is given, to guide antimicrobial
susceptibility
• Positive microbiological urine sample results, without

symptoms, is not indicative of infection. Catheterised patients
often have elevated white blood cells in the urine due to the
presence of the catheter.
• Empiric antimicrobial prescribing should be guided by local

guidance and AMR patterns.

'Start Smart then Focus' antibiotic bundle Ref. Royal College of Physicians Ireland.
LTCF residents with urinary catheters are at increased risk of Case Scenario:
inappropriate antimicrobial prescribing. The figure on the next Mrs Jones, an 82 year old resident at Riverside nursing home
page outlines guidance from Leeds Community Healthcare presents with symptoms of confusion and is disoriented.
for the prevention of catheter associated UTIs in LTCF and She has a background of mild dementia, has limited mobility
this rational approach should form an important part of a LTCF and takes medication for hypertension, atrial fibrillation and
antimicrobial stewardship strategy. Reducing the number of hyperlipidaemia. She has had 6 UTI over the last 12 months. The
unnecessary urine cultures is crucial to reduce the inappropriate nurse conducts a urine dipstick which is positive. The nurse has
diagnosis of CAUTI and inappropriate antimicrobial use. Further contacted the on-call doctor as it is the weekend and requests a
information is available on: prescription for ciprofloxacin.
What steps should be taken by the doctor?
VIEW ANTIBIOTIC •

The doctor should visit the resident gather more clinical
information from the nurse regarding the patients signs
STEWARDSHIP FAQS and symptoms; is there dysuria, urinary frequency/urgency,
DOCUMENT new onset incontinence, fever >38oC, suprapubic tenderness,
haematuria, pain/tenderness?
• If none of the above are present, it is unlikely to be an

infection and ‘watchful waiting’ should be implemented
for the next few days, as well as ensuring that the patient
is well hydrated.

• Any differential diagnoses should be investigated. • The previous results may indicate which antimicrobial the
causative organism would be susceptible too; however, the
• The positive dipstick is not an indicator of infection
prescription should be informed by the microbiology results
• If a UTI is suspected with the presence of clinical signs and once available over the coming days.
symptoms, previous microbiology results of UTI samples from
recent infections should be reviewed and a mid-stream urine
sample should be sent before any antimicrobial is prescribed.

SEPSIS IN LTCF Audit and Feedback:
There is an increasing focus on the early treatment of Sepsis in • Identify key priority areas and focus on them one by one e.g.
LTCFs with the introduction of LTCF specific early warning score conditions accounting for largest proportion of antimicrobial
tools/checklists being introduced to support the treatment of prescribing such as UTI
sepsis in LTCF and reduce the need for resident transfer to acute • Measure the timeliness of interventions on an Early Warning
care setting. Sepsis score
• Conduct audits of antimicrobial prescribing and compare

VIEW UK SEPSIS the results to regional/national LTCF antimicrobial prescribing
guidelines
RESOURCE ARTICLE
The availability of electronic data on antimicrobial prescriptions
can facilitate detailed audits in LTCF, especially if the
prescription data is linked to medical clinical records and/or
ANTIMICROBIAL STEWARDSHIP IN LTCFS microbiology test results.
Goals and outcomes The aforementioned supportive paper for the implementation
of the CMS requirements provides useful information on the
Antimicrobial Stewardship in LTCF Goals:
monitoring of antimicrobial consumption and AMR trends.
1. Introduce a culture to support AMS in your LTCF
2. Consider strategies that are tailored and appropriate for

your setting
VIEW DOCUMENT
3. Have a LTCF AMS Champion to lead the strategy and
garner support
4. Introduce strategies one by one in feasible steps.
5. Benchmark against other, similar LTCF in your region

locally and nationally
6. Improve communication between key stakeholders on

the AMS team and with healthcare providers at points of
resident transfer (e.g. acute hospital – LTCF interface)
7. Give positive and constructive feedback
Measuring AMS in LTCFs:
The CDC Core Elements of Antibiotic Stewardship for Nursing

Homes advises that nursing homes work in a step-wise fashion
and implementing AMS strategies one by one and gradually
adding to the overall strategy over time.

TOOLKIT RESOURCE
PDF ARTICLE
CDC Checklist of core elements for antibiotic
stewardship programs in nursing homes
Measures of antibiotic prescribing use and

outcomes

This checklist recommends the following components for

examining antibiotic prescribing in LTCF:
Figure. Measures of antibiotic prescribing. (adapted from the CDC guideline available from
https://www.cdc.gov/longtermcare/pdfs/core-elements-antibiotic-stewardship-appendix-b.pdf)

CHAPTER 18
AUTHOR: ANDREW M. MORRIS
STEWARDSHIP IN THE
INTENSIVE CARE UNIT
LEARNING OUTCOMES
CHAPTER IS TO:
• Importance and opportunities of ICU Antimicrobial Stewardship
Highlight the importance and • Structures needed for Antimicrobial Stewardship in the ICU
opportunities for antimicrobial
• The best interventions to steward antimicrobials in the ICU
stewardship in ICUs.
• ICU Antimicrobial Stewardship outcome measures
Outline the structures needed
for successful antimicrobial
stewardship in the ICUs. INTRODUCTION
Describe interventions that are Approximately half of intensive care unit (ICU) patients are believed to be infected. The risk
best suited to antimicrobial of infection increases with disease severity.
stewardship in ICUs. These infected patients have an increased risk of death, so the use of antimicrobial agents
is widespread in ICUs, with about three quarters of patients receiving antimicrobials at
Review metrics to reflect
any time. Because most of these antimicrobials are parenteral, broad-spectrum, and often
effectiveness and safety of ICU
relatively new, ICU antimicrobial expenditures usually dwarf similar expenditures elsewhere
in the hospital. Antimicrobial use in ICUs is also associated with increasing antimicrobial
resistance, likely in a complex and multifactorial way. Juxtaposing antimicrobial adverse
consequences including drug-resistant and C. difficile infections with rising antimicrobial
costs and limited discovery of new antimicrobial agents, has resulted in strong calls for
antimicrobial stewardship (AMS) in ICUs.
Despite this, evidence supporting AMS—especially in ICUs—is limited. The greatest benefits
of hospital-based AMS programs appear to be in critical care, but systematic reviews of
AMS programs in ICUs only identified single-centre studies of short duration. Multi-centre
long-term studies are thus a major existing gap in evidence. A Cochrane review on AMS
interventions in hospitals suggests favourable outcomes from enabling over restrictive
interventions.
In this chapter, AMS in ICUs will be considered in terms of program structure, possible
interventions, and outcomes.

CHAPTER 18 - STEWARDSHIP IN THE INTENSIVE CARE UNIT
AMS programs in ICUs, however, are believed to have unique

needs: patients generally have a higher acuity of illness (with
TOOLKIT RESOURCE a higher mortality), pathogens are more often nosocomial and
have higher resistance rates, per-patient antimicrobial utilization
SITE LINKS
is higher and costlier, and opportunities for interprofessionalism
Expert Rev Clin Pharmacol. 2017 Apr;10(4):457-465. have been realized in ICUs more rapidly than in many other
doi: 10.1080/17512433.2017.1293520. Epub 2017 healthcare settings. Accordingly, AMS programs require careful
Mar 2. design and consideration.
ICU AMS Team Membership

Collaborative approach of individual participant
Teams should be interprofessional and multidisciplinary.
data of prospective studies of de-escalation in non-
immunosuppressed critically ill patients with sepsis.
Gutiérrez-Pizarraya A1, Leone M2, Garnacho-

Montero J3, Martin C2, Martin-Loeches I4.
Emerg Med Clin North Am. 2017 Feb;35(1):199-217.

doi: 10.1016/j.emc.2016.09.007.
Antimicrobial Stewardship in the Management of

Sepsis. Pulia MS1, Redwood R2, Sharp B3. (this one
is from ED but has some very good key points
applicable to ICUs like rapid diagnostics, order
sets to guide therapy and stewardship of
diagnostic testing)
Traditionally, discussion around choice of antimicrobial therapy
has been a collaboration between intensivist and either a
microbiologist or infectious diseases physician.
PROGRAM STRUCTURE Over time, the opportunities for broader collaboration and
perspectives have grown to include ICU pharmacists and
ICUs and their staff are supportive of AMS. A recent Canadian
AMS pharmacists. Some programs have started to also
survey found that intensivists were overwhelmingly in support
include infection preventionists, nurses, and even patients or
of AMS, and felt that AMS improved patient care. Despite this,
their advocates (e.g. family, guardians, etc.) Broadening the
AMS programs are not well established in ICUs. The Canadian
team poses early challenges (as there are perceived threats
study showed that few ICUs had a full complement of
to autonomy, challenges with logistics and communication
interventions aimed at improving antimicrobial prescribing.
methods), but over time prove beneficial. An obvious additional
A recent study in Germany was consistent with this finding,
challenge for team membership relates to funding the various
with only a small minority of hospitals even employing an
positions (which is beyond the scope of this chapter). In my
infectious diseases specialist.
experience, although some ICU teams may feel capable of
There are several available resources for general structuring “self-stewarding”, proper antimicrobial stewardship requires an
of AMS programs. These include guidance documents from external person or team to provide a different perspective.
the Infectious Diseases Society of America and the Society
for Hospital Epidemiology of America, National Stewardship
Guidance from Scotland, as well as standards set out by
an increasing number of organizations, including The Joint
Commission, the Centers for Disease Control and Prevention,
Accreditation Canada, and the Australian Commission on Safety
and Quality in Health Care.

ICU Antimicrobial Stewardship Structural Supports

Because of patient complexity and acuity, ICU AMS requires
information optimisation. Empiric therapy should be guided
by recent, accurate antibiograms that are specific to the local
community (for community-acquired infections) and the ICU (for
nosocomial infections). ICUs should also have standardised
approaches to management of common scenarios, that account
for local resistance rates.
De Bus L, Saerens L, Gadeyne B, et al. Development of antibiotic

treatment algorithms based on local ecology and respiratory
surveillance cultures to restrict the use of broad-spectrum antimicrobial
drugs in the treatment of hospital-acquired pneumonia in the intensive
care unit: a retrospective analysis. Crit Care. 2014;18(4):R152.
Dellit TH, Chan JD, Skerrett SJ, Nathens AB. Development of a

guideline for the management of ventilator-associated pneumonia
based on local microbiologic findings and impact of the guideline
on antimicrobial use practices. Infect Control Hosp Epidemiol.
2008;29(6):525-533
Sepsis ventilator-associated pneumonia, intra-abdominal In hospitals and ICUs with computerised physician order
infections, central line-associated bloodstream infections, and entry (CPOE), electronic order sets can facilitate standardising
candidemia are just some common scenarios that should be antimicrobial practice.
protocolised.
Ideally, when ICU teams are reviewing patients, they can
have a temporal snapshot of the patients’ infectious disease
history: their colonisation status, their prior and current
VIDEOS ON THESE TOPICS antimicrobial therapy, and prior and current microbiology results.
Computerised decision support to do this has been available
for many years, but carries considerable expense and so is not
WATCH VIDEOS routinely used in ICUs at present.

INTERVENTIONS Guidance of Empiric Therapy
Diagnostic Stewardship
Most of antimicrobial prescribing in ICUs is empiric.

Accordingly, intensivists require guidance on empiric therapy.
Diagnostic Stewardship Opportunities in Intensive Care Units: Causes The most common conditions where intensivists prescribe
of False Positive Results Driving Unnecessary Antimicrobial Use antimicrobials are community-acquired and ventilator-associated
pneumonia, intra-abdominal infection, undifferentiated sepsis,
and candidemia.
With the complexities of care in the ICU, treatment decisions
can be influenced by a variety of factors. Positive microbiologic
results from urine cultures (in asymptomatic, catheterised
patients), sputum or endotracheal aspirate cultures, or blood
VIDEOS ON THIS TOPIC
cultures drawn through central venous catheters are all likely
to lead to unnecessary antimicrobial prescribing. By limiting
microbiologic testing to foci or organ systems that are likely
WATCH VIDEOS
infected, false positive test results (and subsequent antimicrobial
therapy) will be minimised. Methods to steward diagnostics are
beyond the scope of this chapter. Guidelines can help, although most guidelines do not account
for local resistance patterns, which may change rapidly.
Accordingly, it is best to at least have up-to-date ICU-specific
antibiograms.
VIEW DOCUMENT

Antibiograms according to source (e.g. blood, respiratory tract,

etc.) are recommended, however, the weighted-incidence TIPS FOR COACHING DURING AUDIT
syndromic antibiogram (WISCA) has recently been advocated. AND FEEDBACK
WISCAs consider the various organisms causing clinical
• Come prepared
syndromes, and then list the agents or combinations of agents
Have the list of patients, and try to have as much
that cover the infection. Intensivists should also have access
current information (esp. up-to-date microbiology and
to community-based antibiograms, to guide management of
antimicrobial therapy) as possible.
patients being admitted through the emergency department,
either from independent living, or from long-term care. • Start off with introductions, if necessary
Make sure names and roles are clear for everyone
present
• Allow prescribing team to discuss first
VISIT SITE “Tell me about Ms. X in bed 1”
• Early in the relationship, don’t try to make too many
recommendations
Coaching Perhaps focus on less contentious issues (e.g. dosing).
Antimicrobial stewardship generally requires a variety of Coaching requires a relationship to develop prior to
behaviour change techniques. AMS in the ICU is no different. establishing trust.
An increasingly adopted behaviour change technique involves • Consider setting durations as another relatively
feedback and monitoring, often referred to as prospective easier target
audit and feedback. These are types of coaching. In the ICU, There are published trials on shortened durations (e.g.
coaching can involve routinely scheduled meeting with the ICU ventilator-associated pneumonia, intra-abdominal
team (ideally 3-5 times per week), or meeting with the prescriber sepsis, etc.)
when a new prescription or antimicrobial order is written.
• Streamlining therapy for infections with
Some programs have focused on “priority” antimicrobials
microbiological confirmation is usually straightforward
(recently referred to as reserve antibiotics by the World Health
When a patient is growing penicillin-susceptible
Organization). AMS will involve reviewing whether the use of
Streptococcus pneumoniae, stepping down to penicillin
each antibiotic is “appropriate” or not. Appropriateness is not
should not be contentious
always objective in empiric therapy, so feedback should discuss
• Accept that risk tolerance varies between
whether the need for antibiotics is consistent with the clinical
healthcare providers
picture, and whether the choice, route, dose, frequency, and
Rather than trying to change risk tolerance, try and
duration is appropriate.
characterize a prescriber’s risk. If a prescriber is
unwilling to discontinue empiric coverage for, say,
Pseudomonas aeruginosa, it is far more useful to
first ask what probability he/she would tolerate for
Pseudomonas being the causative agent.
• Make sure each encounter is a learning one
Even mentioning, say, some information on
pharmacokinetics, or mechanisms of resistance may
be enough to provide added value to the coaching
session.
• Be patient
Behaviour change takes time.
• Don’t sweat any single antimicrobial
Although tempting to argue at length over stepping
down from meropenem to, say, cefazolin for S.
aureus bacteremia, arguments over any single patient’s
management is more likely to be harmful than helpful.

Restrictive Methods

Authorisation (requiring approval for an antimicrobial prior to
its use or for future use after a first dose is given) is ill-advised for TOOLKIT RESOURCE
antimicrobial stewardship in the ICU. Because the stakes ARTICLES
are high, any intervention that obstructs workflow and timely
Dresser LD, Bell CM, Steinberg M, Ferguson ND, Lapinsky
patient care is likely to be met with resistance. Additionally, S, Lazar N, et al. Use of a structured panel process to
critically ill patients often have multiple consultants involved, define antimicrobial prescribing appropriateness in critical
and approaches using authorisation do not lend themselves care. J Antimicrob Chemother. 2017. doi: 10.1093/jac/
to a collaborative model that ICUs increasingly employ. dkx341
Evolving Approaches Hebert C, Ridgway J, Vekhter B, Brown EC, Weber SG,

Robicsek A. Demonstration of the weighted-incidence
Selective oropharyngeal and digestive decontamination
syndromic combination antibiogram: an empiric
“Decontaminating” the digestive tract in critically ill patients prescribing decision aid. Infect Control Hosp Epidemiol.
has been extensively studied, albeit in settings with low 2012;33(4):381-8.
antimicrobial resistance. In meta-analyses, and in a large
Spellberg B. The New Antibiotic Mantra—“Shorter Is
multicentre cluster randomised trial, it was associated with
Better”. JAMA Internal Medicine. 2016;176:1254-5. doi:
clinical benefit and low levels of antibiotic resistance. 10.1001/jamainternmed.2016.3646.
Compared with selective oropharyngeal decontamination
(where antibiotics are only topically applied in the mouth), van den Bosch CM, Hulscher ME, Natsch S, Gyssens IC,
Prins JM, Geerlings SE, et al. Development of quality
selective digestive decontamination (involving intravenous
indicators for antimicrobial treatment in adults with sepsis.
and enteral non-absorbable antibiotics) is associated with BMC Infect Dis. 2014;14:345.
lower mortality, reduced length of stay, and lower rates of
ICU-acquired bacteremia and candidemia. Concerns of
antimicrobial resistance in settings with higher prevalence of
antimicrobial resistance have prevented widespread adoption
of this approach. (ii) Patient has a proven or probable infection and the
antimicrobial therapy is not included in the patient’s allergy
Biomarker-guided therapy history with clear contraindications.
Biomarkers are measurable substances that reflect a physiologic
(iii) Patient has a proven or probable infection and
or pathologic process. Procalcitonin and, to a lesser extent,
the antimicrobial therapy has no clear and obvious
C-reactive protein are two biomarkers that hold the most
contraindications.
potential for guiding antimicrobial therapy in critically ill patients.
When used—usually using an appreciable decline in biomarker (iv) Patient has a proven or probable infection and the
level from the start of therapy or a single value below a threshold antimicrobial therapy is administered via a route best suited to
value—biomarkers appear to facilitate safe discontinuation of the infection and clinical status of the patient.
antimicrobial therapy. Unfortunately, clinicians seem reluctant to (v) Patient has a proven or probable infection and the
follow biomarker guidance on many patients—probably because antimicrobial therapy is dosed (dose and frequency) sufficiently
of well-founded concerns regarding biomarkers’ abilities to to treat the infection.
definitively rule out active infection. (vi) Patient has a proven or probable infection and the
antimicrobial therapy is expected to reach the target site(s).
OUTCOME MEASURES (vii) Patient has a proven or probable infection and the current
Appropriateness antimicrobial therapy duration does not exceed evidence-based
(or accepted) lengths of therapy.
Categorization of Antimicrobial Prescribing Appropriateness
in Critical Care: ANY of the following statements define EFFECTIVE BUT
UNNECESSARY antimicrobial prescribing:
The following statements collectively define APPROPRIATE
antimicrobial prescribing: (i) Patient has a probable infection and the empirical
antimicrobial therapy covers an antimicrobial spectrum that is
(i) Patient has a proven or probable infection and the
too broad OR has a proven infection
antimicrobial therapy covers an antimicrobial spectrum that is
neither too narrow nor too broad. and the antimicrobial therapy targets the identified organism(s)
but is too broad.

(ii) Patient has a proven infection and the antimicrobial therapy patient is not deemed palliative.
includes double coverage for an identified organism where (vii) Patient has clear indications for antimicrobial prophylaxis
double coverage is not known or not generally accepted to be but is not prescribed prophylactic antimicrobial therapy.
superior.
(iii) Patient has a proven or probable infection and the Antimicrobial stewardship, ideally, guides the appropriate
antimicrobial therapy is administered by a parenteral route use of antimicrobials. However, appropriateness is inherently
when an enteral route is possible and expected to be equally subjective, and changes over time as new research better
effective. defines the role of empiric and definitive antimicrobial therapy.
Recently, using Delphi consensus-based methodology, criteria
(iv) Patient has an infection and the antimicrobial therapy is
and categories of appropriateness of antimicrobial therapy in
dosed too high and/or too frequently to treat the proven or
ICUs was developed. The authors categorised antimicrobial
probable infection.
therapy in the ICU as “appropriate”, “effective but unnecessary”,
(v) Patient has a proven or probable infection and the current “inappropriate”, and “under-treatment”.
antimicrobial therapy duration exceeds evidence-based (or
accepted) lengths of therapy. Quality Indicators
ANY of the following statements define INAPPROPRIATE One way to improve the use of antimicrobials in the ICU, is
antimicrobial prescribing: to ensure that overall care of infectious diseases is of a high
quality. Process measures can help guide therapy. A Dutch
(i) Patient does not have an infection and has no clear indication
group recently published quality indicators for antimicrobial
for the prescribed antimicrobial therapy.
therapy in sepsis: obtain cultures;
(ii) Patient had suspected infection but has no objective
prescribe empirical antimicrobial therapy according to the
evidence of active infection AND has not objectively
national guideline; start
responded to a reasonable (at least 3 days) empirical course of
antimicrobial therapy. intravenous drug therapy; start antimicrobial treatment within
one hour; and streamline
(iii) Patient is receiving antimicrobial therapy for prophylaxis or
pre-emptive treatment without evidence to support the practice antimicrobial therapy. Similar indicators have not been
and the risk and severity of anticipated infection is expected or published for other relevant conditions seen in the ICU, but
known to be low. modifications could likely be developed on a local level.
(iv) Patient has a proven or probable infection but is Antimicrobial Use

prescribed a drug for which there is a clear, life-threatening Antimicrobial use measures are generally useful for trending
contraindication. and benchmarking purposes, but lack clinical relevance. For
ANY of the following statements define UNDER-TREATMENT in example, an ICU with a large number of neutropenic patients
antimicrobial prescribing: and high levels of antimicrobial use and cost may be more
appropriate in their prescribing than a cardiac ICU (with primarily
(i) Patient has a proven or probable infection but the prescribed
patients with heart failure and acute coronary syndromes) who
antimicrobial therapy has insufficient activity to treat the
use 20% fewer antimicrobials. This is why appropriateness
identified or anticipated organism(s).
is the ideal single measure. Regardless, all measures of
(ii) Patient has a proven or probable infection but the prescribed antimicrobial use should be standardized according to patient
antimicrobial therapy is not administered via a route best suited volume, usually per 1000 patient-days. Below are different
to treat the infection. means of measuring use.
(iii) Patient has a proven or probable infection but the prescribed
antimicrobial therapy is dosed too low or infrequently to treat Defined Daily Doses (DDD)
the infection. These are relatively easy to collect and provide a good
indication of overall antimicrobial use. Often, ASPs will focus
(iv) Patient has a proven or probable infection but the prescribed
on “reserve” antibiotics, such as carbapenems. A concern
antimicrobial therapy is not expected to reach the target site(s).
with DDDs relates to dosing modifications in the ICU, where
(v) Patient has a proven or probable infection but the prescribed some DDDs will underestimate drug exposure (e.g. in the
antimicrobial therapy was discontinued prior to completing a setting of dosage adjustment for dialysis) and some others will
course that is evidence-based (or accepted to be sufficient). overestimate drug exposure (e.g. in the bariatric population, or
(vi) Patient has a proven infection and requires antimicrobial those with central nervous system infection).
therapy but is not prescribed antimicrobial therapy and the

Days of Therapy (DOT) SUMMARY

These tend to be more difficult to collect than DDDs, capture a
The ICU is, in many ways, the perfect setting for antimicrobial
similar measurement, and largely avoid issues related to dosing
stewardship: substantial drug-resistance, prevalent antimicrobial
modifications seen with DDDs.
use, and a geographically-confined interprofessional patient
Cost care setting. By taking a methodical approach to antimicrobial
Cost does not correlate well with appropriateness of most other stewardship—focusing on diagnostic stewardship, guiding
measures of antimicrobial quality. It marginally reflects how empiric therapy based on local data and best available evidence,
broad-spectrum an antibiotic is. and coaching—antimicrobial use can be optimised. The most
important outcome to measure is appropriateness, although it
Antimicrobial Resistance remains a challenge to do this reliably.
At this point in time, the magnitude of measurable benefit for
reducing antimicrobial resistance and antimicrobial resistant
organisms (AROs) is uncertain. Although reducing or controlling
AROs is an oft-cited justification for antimicrobial stewardship,
the evidence that measurable improvements can be seen in ICUs
is weak at present. Regardless, I always recommend following
C. difficile and candidemia rates, supplemented by antibiogram
monitoring of common non-fermenting Gram negative bacteria
such as Pseudomonas aeruginosa, and Acinetobacter species.
Balancing Measures
The literature is rather consistent that antimicrobial stewardship
is safe. Nevertheless, introducing stewardship into ICUs may
result in hesitant clinicians who are concerned about patient
outcomes. Tracking mortality, length of stay, ventilation days,
and other markers of patient safety are recommended. Using
severity metrics (e.g. APACHE-2 scores) is also recommended,
to ensure that mortality risk doesn’t change over time.

CHAPTER 19
AUTHOR: HAIFA LYSTER
STEWARDSHIP IN THE
IMMUNOCOMPROMISED
PATIENT SETTING
LEARNING OUTCOMES
CHAPTER IS TO:
• Define an immunocompromised host
Describe the challenges
• Evaluate the role of net immunosuppression in mediating the risk of infections in
to Antimicrobial
susceptible hosts
Stewardship (AMS) in the
• Describe barriers to antimicrobial stewardship (AMS) in the immunocompromised
immunocompromised host.
patient setting
Outline the opportunities • Identify the opportunities for AMS in immunocompromised hosts
for AMS in the • Discuss the role of multi-disciplinary working in delivering AMS in this setting
immunocompromised
• List considerations for antimicrobial treatment in this special patient population
patient setting.
THE CHAPTER WILL INTRODUCTION

ALSO DEFINE: Antimicrobial stewardship (AMS) in the immunocompromised is a little more challenging
The concept of ‘Net state of as patients have a reduced ability to immunologically respond (if at all) to an infection.
immunosuppression’ as a A wide-range of conditions can result in immune-compromise including primary
guide to differential treatment immunodeficiency, diseases such as advanced diabetes and HIV, severe malnutrition and
options. drug-induced immune compromise, such as during the treatment of cancer, inflammatory
conditions or post-transplantation. Advances in the management of cancer, solid organ
The challenges to diagnosing transplantation (SOT) and hematopoietic stem-cell transplantation (HSCT) have improved
and treating infections in this patient survival, but the subsequent immunocompromised state, regardless of the
special patient population. mechanism, means that these patients are at increased risk of infection.
There are a number of challenges to diagnosing and treating infections in this patient
group:
• Patients are susceptible to a broad spectrum of infections, including to pathogens

with normally low pathogenic potential (opportunistic pathogens), which can
progress rapidly
• Timely active anti-infective therapy is required for good outcomes, but can be
complicated by delays in processes of care and, for example, drug-drug interactions
• The physiological parameters used to guide, for example, the starting and stopping
of antibiotic therapy in immunocompetent patients do not apply

CHAPTER 19 - STEWARDSHIP IN THE IMMUNOCOMPROMISED PATIENT SETTING
• Invasive diagnostic (e.g. bronchoscopy) and/or less commonly

used blood tests (e.g. CMV PCR, cryptococcal antigen,
galactomannan) may be required to confirm infection
• The required length of antimicrobial therapy is even more

poorly defined in immunocompromised patients than in the
immune-competent
• Multidrug-resistant organisms (MDROs) such as Clostridium

difficile, vancomycin-resistant enterococci (VRE) and
carbapenem-resistant Enterobacteriaceae (CRE) are
common due to repeated and prolonged broad-spectrum
antimicrobial courses.
HOW ARE ANTIBIOTIC

STEWARDSHIP EFFORTS
DIFFERENT FOR
IMMUNOCOMPROMISED
PATIENTS? INTERVIEW
WATCH VIDEO
Broad-spectrum antimicrobial agents are commonly used in

areas of the hospital where immunocompromised patients are
managed, such as haematology and oncology units, and often
account for a high proportion of overall hospital use (Fig. 1).
Such areas are clearly excellent ‘targets’ for AMS and should
FIGURE 1
be prioritised.
Diagrammatic representations of broad-spectrum antibiotic use
Implementation of AMS programs have been associated with in Haematology & Oncology compared to other wards at a UK
lower mortality rates in cancer patients (Fig. 2) and reduced teaching hospital
medication errors in hospitalised HIV patients. There are
currently no AMS guidelines in SOT patients.
FIGURE 2
Kaplan–Meier curves of 28-day mortality according to adherence to
ASP
From: Rosa RG, Goldani LZ, dos Santos RP. Association between
adherence to an antimicrobial stewardship program and mortality
among hospitalised cancer patients with febrile neutropaenia: a
prospective cohort study. BMC infectious diseases. 2014;14:286.
https://bmcinfectdis.biomedcentral.com/
articles/10.1186/1471-2334-14-286

Fungi and viruses and therefore infection, is greatest. The changing timeline
While AMS usually refers to antibacterial agents, in of infection after SOT can guide prophylactic and treatment
immunosuppressed patients AMS should also include antifungal strategies; during periods of augmented immunosuppression,
and antiviral therapies, which are commonly empirically used for example, for the treatment of rejection (cellular- or
in the management of, for example, non-resolving neutropenic antibody-mediated), the infection risk ‘clock’ resets to the
sepsis. There is a high mortality and morbidity associated with initial transplant time-point. Although assessing a patient’s net
invasive fungal infections such as Candida species, aspergillosis state of immunosuppression can be challenging, it is useful in
and crypotococcus, coupled with diagnostic difficulties, which assessing what infections the patient may be at risk of and what
often results in overuse of antifungal agents, combination level of investigation and antimicrobial intervention is therefore
therapies and prolonged treatment duration (see e-book chapter justified (see Fig. 3). Scoring systems such as the MASCC
on antifungal stewardship). There are a number of opportunistic score for febrile neutropenia have been developed and are
viral infections; the most common is cytomegalovirus (CMV), recommended in some guidelines to identify lower risk patients
where appropriate antiviral strategies are important to improve who can be treated, for example, with an early switch from IV
outcomes. Also, community-acquired respiratory viruses to oral antibiotics or on an outpatient basis with either oral or IV
e.g. respiratory syncytial virus (RSV), adenovirus, human therapy, although clinical judgement remains of primacy.
metapneumovirus are associated with poor outcome in immuno-
compromised patients, however, consensus guidelines on their
management is lacking. VISIT MASCC RISK INDEX
SCORE ARTICLE
AMS IN THE IMMUNOCOMPROMISED
NOT JUST ANTIBACTERIALS
"HIV-infected T cell" flickr photo by NIAID https://flickr.com/photos/

niaid/6813384933 shared under a Creative Commons (BY) license
Net state of immunosuppression

FIGURE 3
Immunosuppressed patients are not all the same. The concept Timeline of post-transplant infections
of a ‘net state of immunosuppression’ is complex and is
From: Fishman JA1. Infections in immunocompromised hosts and organ
based on clinically synthesising a combination of factors that transplant recipients: essentials.
may impact on the patient’s current immune status, such as
Liver Transpl. 2011 Nov;17 Suppl 3:S34-7. doi: 10.1002/lt.22378
immunosuppressive agents, neutropenia, malnutrition and
comorbidities, as well as infections with immunomodulating http://onlinelibrary.wiley.com/doi/10.1002/lt.22378/full
viruses (e.g. HIV). The net state of immunosuppression can
vary considerably between patients and there is intra-patient
variability over time. For example, transplant patients take
multi-drug regimens of immunsouppressants with higher doses
during the early period post-SOT when the risk of rejection,

CHALLENGES TO AMS IN THE

IMMUNOCOMPROMISED INCIDENCE
Broad spectrum of potential infections
Infections remain a major source of morbidity and mortality in
OF CRE
immunocompromised patients, which can be due to common
pathogens, but there are also a large number of opportunistic
0.4% TO 26.3%
organisms. However, the suspicion of certain infections is higher IN SOT
at different time points; accurate diagnosis is clearly important in
guiding appropriate therapy. There are a number of opportunistic
infections requiring an effective strategy for prophylactic or CRE ASSOCIATED
pre-emptive antimicrobials; e.g. bacteria such as Mycobacterium
species, fungi such as Aspergillus fumigatus or Pneumocystis
MORTALITY
jiroveci (PJP) and viruses such as CMV and hepatitis B. It is also
of note that there are specific types of infections associated with
33% TO 100%
sub-groups of immuno-compromised patients; e.g. BK virus and
IN HSCT/HAEMATOLOGICAL
renal transplant recipients and cryptococcal infection and HIV.
MALIGNANCY
Awareness of whether new chemotherapeutic agents,
Created from: Stephanie M. Pouch & Michael J. Satlin (2017)
immunosuppressants and other immunomodulatory agents are
Carbapenem-resistant
associated with particular infections (e.g. hepatitis B reactivation
with rituximab, viral infections (in particular CMV) with Enterobacteriaceae in special populations: Solid organ transplant
recipients, stem cell
alemtuzumab, and bacterial and fungal infections with sirolimus)
is important and can help guide pre-emptive management and transplant recipients, and patients with hematologic malignancies,
AMS (e.g. knowing when something is not required). Virulence, 8:4, 391-402, DOI:
10.1080/21505594.2016.1213472
Antimicrobial resistance
http://dx.doi.org/10.1080/21505594.2016.1213472
CRE are an emerging global public health concern with mortality
rates of 40% in SOT recipients and 65% in patients with
haematologic malignancies. Antibiotics with activity against CRE

have a number of limitations in terms of either adverse effects
or pharmacokinetics, and combination antimicrobial therapy
TOOLKIT RESOURCE
is often used. The rapid administration of active antibacterial SUGGESTED READING
agents against Gram-negative bacteria is clearly important
The role of antibiotic stewardship in limiting
in immunocompromised patients (e.g. neutropenic sepsis);
antibacterial resistance among hematology
however, in many countries ‘traditional’ empiric regimens may
patients. Gyssens IC, Kern WV, Livermore DM; ECIL-
not be active against CRE or extended-spectrum beta-lactamase
4, a joint venture of EBMT, EORTC, ICHS and
(ESBL) producers. Although modern molecular methods are
ESGICH of ESCMID. Haematologica. 2013
shortening the time to identification of pathogens in well-
Dec;98(12):1821-5
resourced hospitals, and of antibiotic sensitivity testing, in many
centres, even in the developed world, this can still take 2 to 3
The global challenge of carbapenem-resistant
days. Whether guideline-based empiric regimens provide cover
Enterobacteriaceae in transplant recipients and
for highly resistant bacteria depends on the local epidemiology
patients with hematologic malignancies. Satlin MJ,
of such infections, emphasising the importance of surveillance
Jenkins SG, Walsh TJ. Clin Infect Dis. 2014
specific to immunocompromised patient groups.
May;58(9):1274-83
TOOLKIT RESOURCE
SITE LINK
Public Health England Carbapenemase-producing
Enterobacteriaceae toolkit

Diagnostics
Obtaining diagnostic certainty of infection is further
complicated since patients may present with more than
one pathogen simultaneously. Colonisation by a number
of pathogens is a genuine risk and needs to be accurately
differentiated from active or invasive disease in order to avoid
unnecessary prescribing.
Facilitating rapid and accurate diagnostics would lead to early,

targeted antimicrobial therapies and support AMS. However,
microbiology laboratories often outsource tests infrequently
used with a consequent lag time to the results; teams caring
for immunocompromised patients often disproportionately
request these tests resulting in delay and impact on clinical
decisions and AMS. Diagnostic uncertainty and turnaround
delay have been cited as barriers for AMS in
immunocompromised patients (Fig. 4); tests for the diagnosis
of respiratory virus or invasive fungal infections were deemed
the most useful for guiding treatment.
FIGURE 4
Availability of novel diagnostics and azole levels for transplant patients
From: Seo, S., Lo, K., & Abbo, L. (2016). Current State of Antimicrobial Stewardship at Solid Organ and Hematopoietic Cell Transplant Centers in
the United States. Infection Control & Hospital Epidemiology, 37(10), 1195-1200. doi:10.1017/ice.2016.149 https://www.ncbi.nlm.nih.gov/pmc/articles/
PMC5466005/

Prescriber opposition The golden hour

An important factor in successful AMS in the Neutropenia remains the predominant predisposing factor for
immunocompromised is the perceptions and attitudes of infection in most cancer patients, and neutropenic sepsis is a life
the team of physicians and healthcare professionals looking after threatening complication. A new gold standard ‘door-to-needle’
these patients. To encourage a change in prescribing behaviour, time of 1 hour for the administration of intravenous antibiotics,
it is important to understand and address any similar to that in the Surviving Sepsis Campaign, has been
existing negative beliefs. A survey conducted in a teaching introduced. An audit across the United Kingdom highlighted
hospital assessed the knowledge of and attitudes about only 26% of patients achieved this standard, citing numerous
antimicrobial use and resistance amongst physicians. The risk reasons for the delay, the most common being that antibiotics
of missing an infection, and whether a patient was critically ill were prescribed by a doctor, but their administration delayed
or immunosuppressed, were factors felt to most influence by a nurse or until the patient was transferred to the specialist
antibiotic prescribing. Interestingly, while most agreed that ward followed by a prolonged time to assessment by a junior
antibiotics were overused and were concerned about resistance, doctor. Patient group directives allowing the first dose of empiric
they felt that others, not themselves, overprescribed antibiotics. antibiotics recommended in local guidelines to be administered
Most wanted more education about antibiotics and feedback by an advanced nursing practitioner can help to reduce such
about their own practice. delays, but can potentially lead to over-prescribing in patients
who are subsequently shown not to have neutropenic sepsis
As a preventative measure, broad-spectrum antimicrobials are
or severe infection. Interventions to improve ‘door-to-needle’
often prescribed as a catchall for extended periods, resulting
time and optimise AMS in immunocompromised patients are
in increased costs, antimicrobial resistance and drug toxicity.
not mutually exclusive and should synthesise to improve both.
De-escalation and discontinuation of antimicrobials is often
resisted by clinicians as these patients are deemed ‘sicker’
and/or ‘special-cases’ compared to immune-competent

patients. Junior team members are not empowered or do not
have sufficient confidence or clinical support to discontinue
TOOLKIT RESOURCE
antimicrobial therapy, hence engagement with, and involvement SITE LINK
of, senior clinical colleagues is essential. Antibiotic stewardship in the Cancer Patient,
Dr Rod Quiltz, PharmD – video presentation -
discussed the importance of antibiotic stewardship
CRITICAL ILLNESS AND/OR in the immunocompromised cancer
IMMUNOCOMPROMISED
STATE Drug allergy labelling
FOR >80%
Inaccuracy with antibiotic allergy labelling can drive
inappropriate or inferior anti-infective agent selection or
increased use of broad-spectrum agents. The impact of this
OF DOCTORS may be compounded in immunocompromised patients once, for

example, potential drug-drug interactions are accounted for.
OFTEN OR ALWAYS INFLUENCES PRESCRIBING

Created from: Lilian Abbo, Ronda Sinkowitz-Cochran, Laura Smith, Ella
Ariza-Heredia, Orlando Go´mez-Marı´n, Arjun Srinivasan, Thomas M.
Hooton. Faculty and Resident Physicians’ Attitudes, Perceptions, and
Knowledge about Antimicrobial Use and Resistance Infect Control
Hosp Epidemiol 2011;32(7):714-718
https://www.researchgate.net/publication/51212778_Faculty_and_
Resident_Physicians%27_Attitudes_Perceptions_and_Knowledge_
about_Antimicrobial_Use_and_Resistance

OPPORTUNITIES FOR AMS IN THE Formulary review and restriction

IMMUNOCOMPROMISED Limiting access to antimicrobials is essential to minimise
unnecessary broad-spectrum antimicrobial use and subsequent
There are considerable opportunities for AMS in
resistance. Regular formulary review should not only consider
immunocompromised patients (Fig 5). A recent survey assessing
cost, but also spectrum coverage as per local epidemiology,
the extent of AMS programs at SOT and hematopoetic stem cell
therapeutic efficacy, how access to certain antimicrobials is
transplant (HSCT) centres in the United States found that the top
controlled (e.g. carbapenems) without negatively impacting
5 AMS activities that included immunocompromised patients
patient access and outcome, and include agents required for
were: formulary restriction, guideline development, prospective
both prevention and treatment of common infections in this
audit and feedback, education and dose optimisation8.
patient group (e.g. CMV, fungal, and Gram-negative bacterial
infections). Close working relationships with pharmacy for
contingency planning during drug supply shortages is crucial.
Guidelines
Developing clinical guidelines in collaboration with the cancer
and transplant teams is a core function of AMS occurring
in 76% and 71% of HSCT and SOT centres, respectively8.
Regular review of guidelines taking into account patients’
common co-morbidities (e.g. renal impairment and bone
marrow suppression) will simplify clinical decision-making;
implementation has been shown to improve outcomes even
with partial adherence14.
Neutropenic sepsis: prevention and management in people

FIGURE 5 with cancer. UK National Institute for clinical Excellence (NICE)
From: Antimicrobial stewardship in immunocompromised hosts. Abbo Clinical guideline [CG151]
LM, Ariza-Heredia EJ. Infect Dis Clin North Am. 2014 Jun;28(2):263-79
https://www.researchgate.net/publication/262491931_Antimicrobial_
Stewardship_in_Immunocompromised_Hosts
VISIT NICE ARTICLE
TOOLKIT RESOURCE
SUGGESTED READING
Antimicrobial stewardship in immunocompromised VIEW GUIDELINES
hosts. Abbo LM, Ariza-Heredia EJ. Infect Dis Clin
North Am. 2014 Jun;28(2):263-79
Prospective Audit and Feedback (PAF) / Pre-authorisation

Current State of Antimicrobial Stewardship at Solid
PAF is at the heart of AMS and in the immunocompromised host
Organ and Hematopoietic Cell Transplant Centers
is preferred to pre-authorisation in order to prevent any delay in
in the United States. Seo SK, Lo K, Abbo LM. Infect
therapy in serious infection8. PAF facilitates the re-evaluation of
Control Hosp Epidemiol. 2016 Oct;37(10):1195-200
empiric treatment when further test results are available and has
more potential for educational opportunities, which can include
VIDEO de-escalation and intravenous to oral conversion. A study in
Antibiotic Stewardship in Oncologic Care oncology and HSCT patients utilising PAF was associated with
-- Aliyah Baluch, MD video presentation decreased antimicrobial use and cost without causing harm.15
Antimicrobial dose-optimisation - using pharmacokinetic(PK)

and pharmacodynamics (PD) principles
Optimal antimicrobial dosing requires an understanding of the
relationship between its concentration in the body (PK) and its
clinical response (PD). Because immunocompromised patients

with sepsis may have increased volume of distribution and Multi-disciplinary team working
altered drug clearance pathways, traditional dosing regimens AMS is a multidisciplinary team approach; to work effectively
may not be appropriate. PK-PD optimised dosing regimens there should be close collaboration between the AMS team and
can be extrapolated from critically ill patients16-18; the issues are the HIV, cancer or transplant teams with a shared appreciation
similar in haematological malignancy patients19-21. of the complexities of caring for these patients. Successful
implementation requires an open MDT approach that fits well
with the way HIV, cancer and transplant teams generally work.
IMIPENEM 500MG EVERY A consistent AMS team with regular rounds and MDT attendance
6 HOURS IN FEBRILE is important to increase compliance and acceptance, and

develop trust.
NEUTROPENIA
SUMMARY
53% Applying various AMS strategies in this challenging patient
population is both feasible and essential to optimise treatment
PROBABILITY OF ADEQUATE COVER outcomes whilst minimising antimicrobial resistance at a
FOR COMMON BACTERIAL PATHOGENS time when there is a paucity of novel anti-infectives in the
development pipeline. Many challenges remain so it is important
Created from: Reassessment of recommended imipenem doses in that centres share their experiences and that collaborative
febrile neutropenic patients with hematological malignancies. Lamoth research opportunities are explored.
“
F, Buclin T, Csajka C, Pascual A, Calandra T, Marchetti O. Antimicrob
Agents Chemother. 2009 Feb;53(2):785-7. doi: 10.1128/AAC.00891-08.
Epub 2008 Dec 1.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2630622/
The use of therapeutic drug monitoring can be very useful

So, it’s a little different than
to guide individualised dosing; this practice is established doing stewardship in other
with regards to a number of antibacterial agents (e.g.
aminoglycosides) with increasing utilisation in optimising the populations, but it’s doable,
newer azole antifungals (e.g. voriconazole, posaconazole) and, it just takes a little more time
in some centres, for other antibacterials such as beta-lactams.
Lilian Abbo
Highly active antiretroviral therapy (HAART) and
immunosuppressants are also associated with significant drug-
drug interactions; multidisciplinary stewardship efforts can
reduce medication errors in these patients with pharmacists
playing a major role 2,22
TOOLKIT RESOURCE
SUGGESTED READING
Pharmacokinetic and pharmacodynamics
issues for antimicrobial therapy in patients with
cancer Theuretzbacher U. Clinical infectious
diseases: an official publication of the Infectious
Diseases Society of America 2012;54(12):1785-1792

CHAPTER 20
AUTHOR: SANJEEV SINGH
SURGICAL PROPHYLAXIS
LEARNING OUTCOMES
THE AIM OF THIS
On completion of this chapter, the participant should be able to:
CHAPTER IS TO:
• Ensure rational prescription of prophylaxis
To understand the importance
• Ensurecomplete adherence to guidelines on surgical prophylaxis
and prevention of surgical
site infection. • Understand pharmacokinetics and pharmacodynamics of recommended antibiotics
for surgical prophylaxis
To understand the • Understand Surgical Site Infection versus surgical prophylaxis
pharmacokinetics and
pharmacodynamics of
antibiotics used for surgical BACKGROUND
prophylaxis.
Surgical Site infection is one of the most common healthcare associated infections. SSI
leads to additional hospital stay of 6.5 days at a cost 3,246 Pounds. SSI is an important
outcome measure for surgical procedures.
DEFINITION
Surgical antibiotic prophylaxis is defined as the use of antibiotics before, during,or after a
diagnostic, therapeutic or surgical procedure to prevent infectious complications.This term
is used to describe antimicrobial therapy prescribed to clear infection by an organism or to
clear an organism that is colonising a patient but is not causing infection.

CHAPTER 20 - SURGICAL PROPHYLAXIS
IMPORTANCE
1. World Health Organisation (WHO) Clean Care is safer Care
programme shows that surgical site infection (SSI) is the most
surveyed and frequent type HAI in LMICs and affects up to one
third of patients who have undergone a surgical procedure. In
LMICs, the pooled incidence of SSI was 11.8 per 100 surgical
procedures (range 1.2 to 23.6) 1,2. Although SSI incidence is
much lower in high-income countries, it remains the second
most frequent type of HAI. The European Centre for Disease
Prevention and Control (ECDC) reported data on SSI surveillance
for 2010-2011.
RANKING
The highest cumulative incidence was for colon surgery
with 9.5% episodes per 100 operations, followed by 3.5% for
coronary artery bypass graft,2.9% for caesarean section,1.4% for
cholecystectomy,1.0% for hip prosthesis,0.8% for laminectomy
and 0.75% for knee prosthesis3
TOOLKIT RESOURCE
PDF ARTICLES
1 Allegranzi B, Bagheri Nejad S, Combescure
C,Graafmans W, Attar H, Donaldson L, et
al.Burden ofendemic health-care-
associatedinfection in developing
countries: systematicreview and meta-analysis.
Lancet.2011;377(9761):228-41.
2 Report on the burden of endemic healthare-

associated infection worldwide. A systematic
review of the literature. Geneva: World Health
Organization; 2011.
3 Surveillance of surgical site infections in

RATIONALE Europe2010–2011. Stockholm: European
Centre for Disease Prevention and Control 2013
Surgical Site infection is used to encompass the surgical wound
and infections involving the body cavity, organs, which may
or may not be associated with implants or prosthetic devices.
Prophylactic administration of antibiotics inhibits growth of
contaminating bacteria, and their adherence to prosthetic
implants, thus reducing the risk of infection.
VIEW SLIDE SET

REQUIREMENT/PRE REQUISITE
TO PREVENT SSI
• Pre OP bath with Triclosan with contact time of 2-3mts
a day prior and on the day of surgery
• Use of Clippers
• Fasting Blood Sugar
• Normo-thermia
• Pre op preparation with PVP (7.5%) or Chlorhexidine (2%)
• Appropriate sterilisation practices in OR
• Surgical asepsis
• Disinfection practices in recovery area and wards
• Wound Care
Salient Features for Surgical Prophylaxis:
• Usually, a single first-generation cephalosporin for operations

not expected to encounter anaerobes or a single second-
generation cephalosporin with anaerobic operations based
on local susceptibility patterns is sufficient.
• For clean operations on the skin and subcutaneous tissues

that do not involve any portion of the gastrointestinal tract,
a semi synthetic pencillin resistant to penicillinases, such as
oxacillin or cloxacillin, is probably effective,although there are
limited published data to support this recommendation.
• Administration of antibiotics that are active against enteric

anaerobes for procedures involving the lower gastrointestinal
tract should be considered routine.
• Procedures on the upper gastrointestinal tract should involve

use of antibiotics with activity against Gram-positive cocci
• and common Gram-negative organisms but which are not

active against anaerobes.
SELECTION OF ANTIMICROBIAL AGENT • Procedures that do not enter any portion of the intestinal or
FOR SURGICAL PROPHYLAXIS genitourinary tract are sufficiently covered with antibiotics
1. Characteristics of the ideal agent that are primarily active against Gram-Positive cocci.
2. The comparative efficacy of the antimicrobial agent for • β-Lactam allergies are often cited as a contraindication for
the procedure antibiotic prophylaxis
3. The safety profile • For operations in which the risk is primarily from skin
organisms vancomycin or teicoplanin is a common choice for
4. The patient’s medication allergies patients allergic to β-Lactam. If local susceptibility patterns are
favourable, clindamycin can be used.
• First-generation cephalosporins are the most commonly used

agents for prophylaxis in caesarean section. Concern about
neonatal exposure to antibiotics and the effect on neonatal
sepsis have led to delays in administering antibiotics until
after the umbilical cord has been clamped.

RECOMMENDATIONS
TOPICS WHO SHEA/IDSA CDC NATIONAL ROYAL COLLEGE
2016 2014 (unpublished draft) INSTITUTE FOR OF SURGEONS IN
HEALTH AND IRELAND
2014
CARE EXCELLENCE 2012
2008/2013
Surgical antibiotic Yes I Yes: 1B Yes Yes: 1A
prophylaxis Strong Administer only Administer a Antibiotic Single dose only
recommendation, when indicated. preoperative prophylaxis should unless otherwise
low quality of I antimicrobial not be used indicated. Give an
evidence agent only when routinely for clean additional dose
Administer within
indicated, i.e. based non-prosthetic of antibiotic if the
When indicated 1 hour of incision
on published clinical uncomplicated surgical procedure
(depending on the to maximize tissue
practice guidelines surgery. is prolonged or
type of operation), concentration
and timed so that When antibiotic there is major
surgical antibiotic
a bactericidal prophylaxis is intraoperative
prophylaxis should
concentration of the needed, a single blood loss (>1.5 L in
be administered
agent is established dose of antibiotic adults or 25mL/kg
prior to the surgical
in the serum and intravenously in children). Ensure
incision..
tissues when the on starting that the antibiotic is
incision is made. anaesthesia should given at induction
be considered. (within 60 minutes
However, before
prophylaxis should
be given earlier for
operations in which
a tourniquet is used.
LISTEN TO AUDIO
TIME OF ADMINISTRATION
Antimicrobial prophylaxis should be administered only when
indicated based on published clinical practice guidelines and
timed such that a bactericidal concentration ofthe agents is
established in the serum and tissues when the incision is made.12
• Antimicrobial therapy should be initiated within the 60
minutes prior to surgical incision to optimize adequate drug
tissue levels at the time of intial incision.4
• The half-life of the antibiotic should be considered:5
administration of Vanomycin or a fluroquinolone should
begin within 120 minutes before surgical incision because
of the prolonged infusion timesrequires for these drugs

REPEAT DOSING Clindamycin 6

• To ensure adequate antimicrobial serum and tissue Ertapenem NA
concentrations, repeat intraoperative dosing is warranted Fluconazole NA
for procedures that exceed two half-lives of the drug and for
Gentamicing NA
procedures in which there is excessive blood loss(>1500ml)(4)
Levofloxacinf NA
• Redosing may also be warranted in the setting of factors that
Metronidazole NA
shorten antimicrobial half-life,such as extensive burns.
Moxifloxacinf NA
• The dosing interval should be measured from the time of the
Piperacillin–tazobactam 2
preoperative dose(not from the beginning of the procedure)
Vancomycin NA
• Redosing may not be warranted for patients in whom the
Oral antibiotics for colorectal
antimicrobial half-life is prolonged,such as renal insufficiency.
surgery prophylaxis (used in
• For clean and clean-contaminated procedures, conjunction with a mechanical
additionalprophylactic antimicrobial agent doses should not bowel preparation)
be administered after the surgical incision(12)is closed in the Erythromycin base NA
operating room, even in the presence of a drain
Metronidazole NA
Neomycin NA
TOOLKIT RESOURCE DURATION

SITE LINKS • For surgeries less than 4hrs: Single dose
4 Bratzler DW, Dellinger EP, Olsen KM, et al. • For surgeries greater then 4hrs: 3 doses
Clinical practice guidelines for antimicrobial • In general, repeat antimicrobial dosing following wound
prophylaxis in surgery. Surg Infect (Larchmt) closure is not necessary and may increase the risk for the
2013; 14:73. development of antimicrobial resistance.6-11
12 Sandra , Berríos, Craig et al. Centers for Disease

Control and Prevention Guidelinefor the
Prevention of Surgical Site Infection, 2017. JAMA
Surg. 2017;152(8):784-791
Antimicrobial Recommended Redosing

Interval (From Initiation of
Preoperative Dose)
Ampicillin–sulbactam 2
Ampicillin 2
Aztreonam 4
Cefazolin 4
Cefuroxime 4
Cefotaxime 3
Cefoxitin 2
Cefotetan 6
Ceftriaxone NA
Ciprofloxacinf NA

CONTRIBUTORY FACTORS IN SURGICAL

TOOLKIT RESOURCE SITE INFECTION
1. Nutritional status
SITE LINKS
2. Tobacco use
6 Antimicrobial prophylaxis for surgery. 3. The intraoperative technique
Treat Guidel Med Lett 2012; 10:73.
4. Correct selection, timing and dosing of antibiotics
7 Goldmann DA, Hopkins CC, Karchmer AW, et 5. Age
al. Cephalothin prophylaxis in cardiac valve
6. Gender
surgery. A prospective, double-blind comparison
of two-day and six-day regimens. J Thorac 7. Clean vs. clean/ contaminated surgery
Cardiovasc Surg 1977; 73:470. 8. Blood loss
8 McDonald M, Grabsch E, Marshall C, Forbes A.

Ready Reckoner for Surgical Prophylaxis:(based on ASHP,
Single- versus multiple-dose antimicrobial
IDSA and SHEA report 2013)
prophylaxis for major surgery: a systematic
review. Aust N Z J Surg 1998; 68:388. Procedure 1ST Line agents Alternative Agents
9 Conte JE Jr, Cohen SN, Roe BB, Elashoff RM. in Pts With
Antibiotic prophylaxis and cardiac surgery. A b-Lactam Allergy
prospective double-blind comparison of single- Colorectal Cefazolin + Clindamycin +
dose versus multiple-dose regimens. Ann Intern metronidazole, aminoglycosideg
Med 1972; 76:943. cefoxitin, cefotetan, or aztreonam or
ampicillin fluoroquinoloneh-j,
11 Harbarth S, Samore MH, Lichtenberg D, Carmeli
sulbactam,h metronidazole +
Y. Prolonged antibiotic prophylaxis after
ceftriaxone + aminoglycosideg
cardiovascular surgery and its effect on surgical
metronidazole,n or fluoroquinolone
site infections and antimicrobial resistance.
ertapenem
Circulation 2000; 101:2916.
Hysterectomy Cefazolin, Clindamycin or
ARTICLE cefotetan, cefoxitin, vancomycin +
ampicillin– aminoglycosideg
10 Pollard JP, Hughes SP, Scott JE, et al. Antibiotic sulbactamh or aztreonam or
prophylaxis in total hip replacement. Br Med J 1979; 1:707. fluoroquinoloneh-j
Metronidazole +
aminoglycosideg or
fluoroquinoloneh-j
Vascular and Cefazolin Clindamycin,d
TOPICAL ADMINSTRATION OF cardiac surgery vancomycind
IRRIGATIONS, PASTES, AND WASHES Liver Piperacillin– Clindamycin or
Limited high–quality data are available regarding the use transplantationq,t tazobactam, vancomycin +
of antimicrobial irrigations, pastes, and washes that are cefotaxime + aminoglycosideg
administered topically. Additional high quality data on the safety ampicillin or aztreonam or
and efficacy of topical antimicrobial administration as an adjunct fluoroquinolone
to i.v administration are needed to determine the role of tropical Total joint Cefazolin Clindamycin,d
antimicrobial prophylaxis of every 100 hospitalized patients replacement vancomycind
at any given time, seven in developed and 15 in developing
countries will acquire at least one HAI. The endemic burden of
HAI is also significantly (at least 2-3 times) higher in low-and
middle –income countries (LMICs) than in high-income nations,
VIEW DOCUMENT
particularly in patients admitted to intensive care units, and
neonates

SUMMARY
• Surgical Site infection is one of the most commonhealthcare
associated infections.
• Pre requisite to prevent SSI includespre OP bath with

Triclosan with contact time of 2-3mts a day prior and on the
day of surgery, use of clippers,Fasting Blood Sugar, normo-
thermiaetc
• The ideal surgical prophylaxis antimicrobial would be one that

is most appropriate for the procedure and safe for the patient.
• Antibiotics that require prolonged infusion should be

administered 120 mins prior to surgical incision. Others
should be administered 60 mins prior to surgical incision.
• Redosing is not recommended for surgeries that last less

than 4 hours.
References
1. Allegranzi B, Bagheri Nejad S, Combescure C,Graafmans W, Attar H, Donaldson L, et al.Burden ofendemic health-care-
associatedinfection in developing countries: systematicreview and meta-analysis. Lancet.2011;377(9761):228-41.
2. Report on the burden of endemic healthare-associated infection worldwide. A systematic review of the literature. Geneva: World
Health Organization; 2011.
3. Surveillance of surgical site infections in Europe2010–2011. Stockholm: European Centrefor Disease Prevention and Control;
2013(http://ecdc.europa.eu/en/publications/Publications/SSI(-in-europe-2010-2011.pdf, accessed13 July 2016).
4. Bratzler DW, Dellinger EP, Olsen KM, et al. Clinical practice guidelines for antimicrobial prophylaxis in surgery. Surg Infect (Larchmt)
2013; 14:73.
5. Global guidelines for the prevention of surgical site infection. World Health Organization 2016 http://www.who.int/gpsc/global-
guidelines-web.pdf?ua=1 (Accessed on November 08, 2016).
6. Antimicrobial prophylaxis for surgery. Treat Guidel Med Lett 2012; 10:73.
7. Goldmann DA, Hopkins CC, Karchmer AW, et al. Cephalothin prophylaxis in cardiac valve surgery. A prospective, double-blind
comparison of two-day and six-day regimens. J Thorac Cardiovasc Surg 1977; 73:470.
8. McDonald M, Grabsch E, Marshall C, Forbes A. Single- versus multiple-dose antimicrobial prophylaxis for major surgery: a systematic
review. Aust N Z J Surg 1998; 68:388.
9. Conte JE Jr, Cohen SN, Roe BB, Elashoff RM. Antibiotic prophylaxis and cardiac surgery. A prospective double-blind comparison of
single-dose versus multiple-dose regimens. Ann Intern Med 1972; 76:943.
10. Pollard JP, Hughes SP, Scott JE, et al. Antibiotic prophylaxis in total hip replacement. Br Med J 1979; 1:707.
11. Harbarth S, Samore MH, Lichtenberg D, Carmeli Y. Prolonged antibiotic prophylaxis after cardiovascular surgery and its effect on
surgical site infections and antimicrobial resistance. Circulation 2000; 101:2916.
12. Sandra , Berríos, Craig et al. Centers for Disease Control and Prevention Guidelinefor the Prevention of Surgical Site Infection, 2017.
JAMA Surg. 2017;152(8):784-791.

CHAPTER 21
AUTHORS: DAVID ENOCH & LAURA WHITNEY
ANTIFUNGAL STEWARDSHIP
LEARNING OUTCOMES
CHAPTER IS TO:
• Explain what antifungal stewardship is
Describe what Antifungal • Outline the aims of AFS
Stewardship (AFS) is.
• Outline the advantages and disadvantages of AFS
Outline the very basic • Describe the differences between AFS and AMS
principles medical mycology. • Understand more about diagnosing fungal infections
• Understand more about antifungal resistance
Describe the different ways
• Describe how to do it
antifungals are used.
• Describe ways to start
Outline the advantages and • Describe some of the challenges
disadvantages of AFS.
• Describe who you need
Outline how to start an AFS • Describe what you need

programme. • Describe how you continue
• Describe how you expand
• Reflect the relevance of these elements to their practice
INTRODUCTION
Invasive fungal infections are associated with significant morbidity and mortality. Patients
who develop invasive fungal infections often have highly complex underlying conditions
and this, coupled with poor diagnostic tests, often leads to unnecessary and inappropriate
prescribing of antifungal agents.
Antifungal agents are often not as well tolerated as antibacterial agents and many are
extremely expensive. A number of antifungal drugs also have significant drug-drug
interactions with other medication (especially the triazole drugs). One of the principle
drivers of antimicrobial stewardship has been the rise in antibacterial resistance. Until
recently, this has been of less concern with fungi. There is now increasing resistance to
a number of antifungal agents and Candida auris, which has a relatively high level of
resistance to antifungals, has recently been identified as an emerging problem.
PUBLIC HEALTH ENGLAND CANDIDA

AURIS PAGE

CHAPTER 21 - ANTIFUNGAL STEWARDSHIP
SOME BASIC MYCOLOGY Resistance is mediated primarily through mutations in hot-spot

regions of FKS genes, which encode the echinocandin target
Medically important fungi capable of causing invasive fungal
enzyme (1,3-β-D-glucan synthase). Resistance can emerge on
infection can be broadly split into three categories. They include
therapy.
yeasts (e.g. Candida spp. and Cryptococcus spp.), moulds (e.g.
Azole resistance has also been demonstrated in Aspergillus
Aspergillus spp. and the zygomycetes) and dimorphic fungi (e.g.
fumigatus. Fungal biofilm associated infections are recognised
Histoplasma spp.). The dermatophytes (e.g. Microsporum spp.),
as an escalating clinical problem and are frequently refractory
whilst capable of causing superficial infections, rarely cause
to conventional therapy because of resistance. Studies of fungi
invasive infections
using in-vitro and in-vivo biofilm models have demonstrated
less susceptibility to antimicrobial therapy than planktonic free
floating cells.
Risk factors for invasive Risk factors Risk factors

candidiasis for invasive for invasive
candidiasis candidiasis
on ITU
Critical illness Y Y
Abdominal surgery, with particular Y Y
risk among patients who have
anastomotic leakage or have had
repeat laparotomies
Acute necrotising pancreatitis Y
Haematological malignancy Y
"Candida albicans (1000X magnification)" flickr photo by
MichaelFrancisco https://flickr.com/photos/micodude/6500725393 Neutropenia Y
shared under a Creative Commons (BY) license Solid organ transplantation Y
Solid organ tumours Y
Candida albicans is the most commonly isolated strain of Neonates, particularly low birth Y Y
Candida. Invasive candidiasis is the most common fungal weight
disease among hospitalized patients in the developed world. Broad spectrum antibiotics Y
Invasive candidiasis consists of deep-seated tissue candidiasis Central venous catheter Y Y
(candida in a sterile site) and candidaemia (candida in the
Total parenteral nutrition Y Y
bloodstream). Deep-seated candidiasis may be a consequence
Haemodialysis Y Y
of either direct inoculation or haematogenous spread. Risk
factors for invasive candidiasis are described in table 1 Urinary catheter Y
Invasive aspergillosis is a major cause of invasive mould Glucocorticoid therapy Y

infection which tends to affect the immunocompromised. Fungal colonisation Y
Risk factors include haematological malignancy, solid organ Infection or sepsis Y
transplant recipients, haematopoietic stem cell transplant Mechanical ventilation Y
(HSCT) recipients, solid tumours, HIV/AIDS, an inherited Diabetes Y
immunodeficiency or presence on an ITU.
Acute Physiology and Chronic Y
Health Evaluation II (APACHE II) *
Antifungal resistance
or APACHE III score
Fluconazole resistance (See Fig. 1) has been recognized for
Gastrointestinal bleed Y
several years, especially in C. glabrata (dose dependent) and
C. krusei (intrinsically resistant to fluconazole). Azole resistance Age Y
has also been seen in C. parapsilosis and C. auris. Predictors
TABLE 1
associated with fluconazole resistant Candida spp. include Risk factors for invasive candidiasis.
neutropenia, chronic renal disease, and previous fluconazole * APACHE: Acute Physiology and Chronic Health Evaluation
exposure. Echinocandin resistance is increasingly recognized.

FIGURE 1
Adapted from: Laboratory surveillance of Candidaemia in England, Wales and Northern Ireland: 2016 Health Protection Report Volume 11 Number 32
https://www.gov.uk/government/uploads/system/uploads/attachment_data/file/645312/hpr3217_cnddmia2016.pdf
WHAT IS ANTIFUNGAL STEWARDSHIP (AFS)? AIMS OF AFS PROGRAMME

Antimicrobial stewardship has previously been defined in The aims of AFS programmes include:
chapter 3. Antimicrobial stewardship in immunocompromised • Improved patient outcome
patients is also discussed in chapter 19. Antifungal stewardship
• Maximising drug efficacy
can be defined in the same way as ‘the optimal selection,
dosage, and duration of antifungal treatment that results in the • Minimise drug toxicity
best clinical outcome for the treatment or prevention of infection • Prevent the emergence of breakthrough infections
with minimal toxicity to the patient and minimal impact on • Minimise the development of resistance
subsequent resistance’ (Box 2). • Minimise or mitigate the effects of drug-drug interactions
• Maximise cost efficiency
BOX 2: DEFINITION OF AFS

WHAT ARE THE BENEFITS OF AFS?
The right antifungal
For the right patient, A number of research papers describe the financial benefits
of commencing AFS programmes; reducing inappropriate
At the right time,
antifungal use can lead to significant cost savings due to the
With the right dose,
high cost of many of the drugs.
And the right route
More recently, papers have described benefits in terms of
Causing the least harm to the patient and future patients
improved outcome (e.g. mortality; adherence to guidelines).
With the emergence and rise of antifungal resistance in recent

years, it is becoming imperative that AFS is used in order to (fluconazole) are available over the counter in pharmacies for
reduce antifungal resistance. certain indications.
• Fungal prophylaxis/ treatment courses are often more
WHAT ARE THE DISADVANTAGES OF AFS? prolonged than for antibacterials.
The main disadvantage is one of resources. AFS takes time. • Antibacterial resistance has a significantly higher profile,
Importantly, the people who perform AFS need knowledge, being described as a global emergency, compared to
experience and confidence of dealing with the highly complex antifungal resistance, which is less well defined and
patients who typically suffer from invasive fungal infections. discussed, particularly at international levels.
Many studies of successfully implemented AFS programmes
describe using a multidisciplinary approach (e.g. antimicrobial
pharmacist plus an infection specialist) which increases the
resources required.
WHAT ARE THE DIFFERENCES

BETWEEN ANTIFUNGAL STEWARDSHIP
AND ANTIMICROBIAL STEWARDSHIP (AMS)?
There are a number of differences between AFS and AMS.
• There are fewer diagnostic and monitoring tests available
for fungal infections than for bacterial infections and staff
are generally less confident in interpreting results. Fungal
diagnostics may be unavailable in some hospitals or the
turnaround time may be so long as to render them ineffective, "Money" flickr photo by Got Credit https://flickr.com/photos/
leading to empirical treatment of infections. Rational gotcredit/33810597472 shared under a Creative Commons (BY) license
prescribing relies on being able to accurately characterise
the infection.
• There is a greater wealth of experience with bacterial
FUNDING OF ANTIFUNGALS AND ITS
infections compared to fungal infections. This can make the
EFFECTS ON AFS
choosing of antifungal agents for protocols difficult for those Due to their high costs the majority of antifungal agents
involved in approval and implementation of such protocols (liposomal amphotericin B, voriconazole, posaconazole,
and formulary submissions. isavuconazole and the echinocandins) are not included within
treatment tariffs in England. The exception is for patients within
• Staff are less familiar with fungal infections and their
100 days of a bone marrow transplant and those on ITU, where
treatments compared with bacterial infections. This is a
treatment tariffs are considered to be sufficient to fund any
reflection of the fact that they may not have received in-depth
antifungal agents required. Some specialist tariffs exist for
education on treating fungal infections as it is not regularly an
management of patient groups (for example at the national
area of focus for medical school curricula. Furthermore,
aspergillosis centre in Manchester). Usage of these drugs is
fungal infections are rarer than bacterial infections so the
reported to NHS England on a monthly basis through SLAM
majority of healthcare professionals will not have as much
(Stop, Look, Assess, Manage) reporting and any expenditure
experience in managing them.
refunded in full. When cheaper generic drugs become available
• Patients requiring antifungal therapy are often on complex this does not automatically change their status to within tariff.
medication regimens and therefore toxicity and drug-drug
Thus, there is little incentive for English hospitals to fund
interactions seem to be more of an issue than when treating
resources for antifungal stewardship, which as described above
bacterial infections.
is complex and time consuming and to exert its maximal effect
• Fungi are structurally similar to human cells, meaning that requires the introduction of specialist diagnostics, which add to
drugs used to target them can often have side effects and the cost. Some interventions may reduce costs in in-tariff drug
interactions. use so may be worth pursuing, but most antifungal use occurs
• AFS is almost exclusive to secondary care; the majority of outside tariff.
prescribing is within this sector, with most antifungals being In Scotland, Wales and Northern Ireland there is not a purchaser-
restricted to hospital use only. Although systemic antifungals provider split. Health Boards are responsible for the cost of all

medicines supplied from their annual budgets so the Health

Board benefits from any efficiency savings resulting from
BOX 3: DEFINITIONS OF INVASIVE FUNGAL
stewardship directly.
DISEASE (IFD) (EORTC-MSG CRITERIA)
Health services outside the UK may have different funding
Possible: Those cases with appropriate host factors and sufficient
systems. It can be useful to try and understand the system
clinical evidence consistent with IFD, but for which there was no
you use.
mycological support
TYPES OF ANTIFUNGAL USE Probable: Those cases with a host factor, clinical features, and
mycological evidence of IFD
Antifungal agents are used in a wide variety of ways in different
populations. There is also great variability of use between Proven: Those cases in which fungal elements in diseased tissue
different patient groups. This is most likely to be due to are demonstrated for most conditions
differences in patient populations, risk factors, environmental
considerations and prior antibacterial and antifungal use.
Antifungal agents are used to prevent infections in some From: Revised Definitions of Invasive Fungal Disease from the
susceptible patients (i.e. prophylaxis). European Organization for Research and Treatment of Cancer/
Invasive Fungal Infections Cooperative Group and the National
They can be used empirically, i.e. an antifungal agent is used
Institute of Allergy and Infectious Diseases Mycoses Study Group
in a susceptible patient who has clinical evidence of infection (EORTC/MSG) Consensus Group https://academic.oup.com/cid/
and is not improving with an antibacterial agent, so is presumed article/46/12/1813/297334/Revised-Definitions-of-Invasive-Fungal-
to have a fungal infection (but there is no actual clinical or Disease
pathological evidence of fungal infection).
For a diagnosis of proven IFI, specimens must be obtained
DIAGNOSING FUNGAL INFECTIONS
by a sterile technique from a normally sterile site. Invasive
mould infection is proven if hyphae are seen in a histological As described above, diagnosing fungal infections can be difficult.
or cytological specimen (with evidence of tissue damage seen Access to timely diagnostics is essential. The British Society
either in the biopsy material or “unequivocally” by imaging) or for Medical Mycology has provided guidelines / best practice
a mould is grown in culture from that specimen with clinical recommendations for microbiology laboratories (and
or radiological evidence of infection at the site from which the histopathology and radiology; Schelenz et al 2015). Whilst not
specimen was taken. Systemic yeast infection would be proven all tests need to be performed locally, a short turnaround time
on the same evidence as above or if the yeast was grown in a is essential to affect patient management. Unfortunately, these
blood culture. A diagnosis of probable IFI requires a combination guidelines do not make recommendations as to acceptable
of host factors and microbiological and clinical criteria, whereas turnaround times. However, a turnaround time of <48 hours
a diagnosis of possible IFI requires host factors and clinical would be ideal for serological and molecular tests.
features. The diagnostics (and how to interpret them) required include:
Treatment decisions therefore depend on: • Galactomannan screening of serum (two times per week)
• Host factors from patients with haematological malignancies at high risk
• Clinical features of invasive aspergillosis should be considered in those not
• Microbiology results receiving mould-active prophylaxis; optical density (OD) index
o Host factors threshold of 0·5 has a high negative predictive value,
• Factors that render a patient susceptible to IFI include: enabling invasive aspergillosis to be excluded
• Neutropenia • Galactomannan testing of BAL from patients at high risk
• Allogeneic HSCT recipient of invasive aspergillosis should be considered, although the
• T-cell immunosuppression current OD index cut-off of 0·5 might change. Some centres
• Prolonged corticosteroids (>3 weeks) use a cut-off of between one and three.
• Inherited severe inherited immunodeficiency • β-D-glucan screening of serum from patients at high risk
o Clinical features of invasive fungal disease should be considered; a negative
• Clinical features include pyrexia, cough and sinus pain result has a high negative predictive value, enabling
etc. They also include radiological features (particularly invasive fungal disease to be excluded. These high-risk
CT changes). categories include immunosuppressed patients and
o Microbiology tests intensive care patients.
• These are discussed later in the chapter. • PCR screening of serum for aspergillus from patients at high

risk of invasive fungal disease should be considered; a AFS: HOW DO YOU DO IT?
negative result has a high negative predictive value, enabling
How do you start?
invasive fungal disease to be excluded
Initially it is important to understand antifungal use in your
• Combination testing with aspergillus PCR plus another patient population. Audit and surveillance (Fig. 2) can be helpful,
antigen test improves the positive predictive value and both to identify particular challenges to address or to identify
diagnosis of invasive fungal disease poor practice to modify. It can also be used to persuade clinical
and managerial colleagues of the need for a stewardship
programme and provide some useful data to assess the efficacy
of your interventions.
a) Haematology, infectious diseases and oncology healthcare group
b) Surgery healthcare group
FIGURE 2
Example of surveillance of anti-fungal defined daily doses at a UK teaching hospital, 2013-2018

A good starting point is to create or review guidelines and

clinical pathways in line with local epidemiology (especially for
TOOLKIT RESOURCE invasive candidiasis) and patient population. Guidelines that are
available already that can be adapted are provided in resource
SITE LINK - UK
toolkit. The availability and turn-around-time of diagnostics
Ashbee HR, Barnes RA, Johnson EM, Richardson MD, should be considered within this process.
Gorton R, Hope WW. Therapeutic drug monitoring Ideally funding for the service should be agreed prior to
(TDM) of antifungal agents: guidelines from the commencing the programme and resourced from those
British Society for Medical Mycology. J Antimicrob expecting to see reductions in expenditure (usually
Chemother. 2014; 69: 1162-76 commissioners in England).
Schelenz S, Barnes RA, Barton RC, Cleverley JR, Aim to start small by choosing a particular clinical area or a
Lucas SB, Kibbler CC, Denning DW; British Society small group of drugs. Building relationships and knowledge
for Medical Mycology. British Society for Medical and influencing prescribing can be easier if you dedicate your
Mycology best practice recommendations for the time to working with a small group of colleagues and patients.
diagnosis of serious fungal diseases. Lancet Infect Haematology and intensive care units are typically good places
Dis. 2015; 15: 461-74. http://www.thelancet.com/ to start, usually being the biggest users of antifungals. Specialist
journals/laninf/article/PIIS1473-3099(15)70006-X/ centres may also find transplant and upper gastrointestinal
fulltext surgery to be heavy users of antifungal agents. Another option
is to use audit data or local knowledge to identify areas of
SITE LINK - EUROPE antifungal use that require optimisation. Interventions may be
European Conference on Infections in Leukaemia addressed incrementally according to resources, risk levels, or
(ECIL) guidelines page ease of implementation
European Society Clinical Microbiology and

EXAMPLES OF AFS THAT WORK INCLUDE:
Infectious Diseases (ESCMID) guidelines page
• Reviewing all patients on voriconazole to ensure TDM is
SITE LINK - NORTH AMERICA undertaken and results outside therapeutic range are acted
upon could be implemented relatively easily and with a
Pappas PG, Kauffman CA, Andes DR, Clancy CJ, Marr
limited stewardship team (i.e. with just a pharmacist). A
KA, Ostrosky-Zeichner L, Reboli AC, Schuster MG,
summary of the need for TDM is provided in table 2
Vazquez JA, Walsh TJ, Zaoutis TE, Sobel JD. Clinical
Practice Guideline for the Management of • Reviewing all candidaemia patients and ensuring all patients
Candidiasis: 2016 Update by the Infectious Diseases complete all aspects of the care bundle (Gouliouris et al
Society of America. Clin Infect Dis. 2016 Feb 2016):
15;62(4):e1-50 • Adequate empirical therapy
Patterson TF, Thompson GR 3rd, Denning DW, • timely treatment

Fishman JA, Hadley S, Herbrecht R, Kontoyiannis DP, • lines reviewed
Marr KA, Morrison VA, Nguyen MH, Segal BH, • echocardiography
Steinbach WJ, Stevens DA, Walsh TJ, Wingard JR,
• repeat blood cultures
Young JA, Bennett JE. Practice Guidelines for the
Diagnosis and Management of Aspergillosis: 2016 • rationalised antifungal therapy
Update by the Infectious Diseases Society of • Managing patients with candidaemia can be reviewed
America. Clin Infect Dis. 2016 Aug 15;63(4):e1-e60 by watching the following link
Freifeld AG, Bow EJ, Sepkowitz KA, Boeckh MJ, Ito

JI, Mullen CA, Raad II, Rolston KV, Young JA, Wingard
JR; Infectious Diseases Society of America. Clinical
practice guideline for the use of antimicrobial agents
WATCH VIDEO
in neutropenic patients with cancer: 2010 update by
the infectious diseases society of america. Clin Infect
Dis. 2011 Feb 15;52(4):e56-93. doi: 10.1093/cid/cir073.

• Prospectively collect data on your stewardship activities –

design a database. Or collaborate with a centre that already
has one! Previous AFS programmes have collected the
following data: patient demographics; antifungal drug;
indication for therapy; site of infection; causative organism,
if identified; interventions made during stewardship activities
(including whether these were accepted); length of stay and
in-hospital mortality. Monitoring antifungal consumption and
expenditure and candida epidemiology is also key
GRADE quality of
Antifungal evidence and strength Prophylaxis Treatment Toxicity
of recommendation
Evidence quality Moderate Moderate Moderate

Itraconazole
recommendation Strong Strong Weak
Evidence quality Low High High

Voriconazole
recommendation Weak Strong Strong
Evidence quality Moderate Moderate High

Posaconazole
recommendation Strong Strong Strong against
Evidence quality High High High

Fluconazole
recommendation Strong against Strong against Strong against
Evidence quality Low Moderate

Flucytosine NA
recommendation Weak Strong

Echinocandins

Polyenes
TABLE
summary of need for therapeutic drug monitoring when using antifungal agents (based on Ashbee et al)
AFS: WHAT ARE THE CHALLENGES? WHO DO YOU NEED TO INVOLVE?

Funding – getting this from the commissioners (who will be the Who are the stakeholders?
ones who see the cost benefits) can be difficult. NHS England These include Commissioners, Trust managers/financial officers,
is currently looking at how to incentivise AFS. In the meantime, clinicians in high risk areas (e.g. haematology, oncology, ITU,
Trusts could initiate programmes focusing on in tariff use. respiratory, transplant), microbiology, infectious diseases,
Time – AFS is more time consuming compared to antibacterial pharmacy, and patients.
stewardship. The MDT need dedicated time in job plans and
consideration of how work will be covered during annual leave/
sickness absences.
Expertise – try to link with centres with embedded stewardship

programmes and learn from them
Persuasive ability – it is often difficult to stop/modify

antimicrobials in critically ill immunocompromised patients

is currently not recommended by the manufacturer though

it is available. TDM is not required for amphotericin B or the
echinocandins. Flucytosine monitoring is recommended for all
patients receiving treatment.
Surveillance
Numbers and types of infections seen (proven/probable/
possible) and species if known, candidaemia epidemiology
– proportion of albicans/non-albicans, with a particular eye
on more difficult to treat species – C. auris, C. glabrata, C.
krusei. Monitor the proportion of candidaemias susceptible to
fluconazole and echinocandins, preferably looking at MIC data
and reporting mode MIC.
Outcome data
These can include: length of stay, in-patient mortality, costs
of program versus costs saved, in-tariff costs versus outside
tariff. Intervention rates, types and acceptance. Quality
"Tools" flickr photo by Kimberlie Kohler https://flickr.com/photos/ indicator data – guideline compliance, IV-PO switch, proportion
bbbellezza/5542980497 shared under a Creative Commons of empiric prescriptions stopped within a week if no IFI
(BY-SA) license
diagnosed, TDM done when indicated – results within range
or acted upon if outside.
WHAT DO YOU NEED?

Guidelines
For diagnosis of infections and prophylaxis and treatment
in groups of patients frequently seen in your setting. Audit
standards should be set within guidelines ideally.
Diagnostics
Rapid turn-around time (TAT) is essential. It is likely to be
necessary to work with clusters of local labs as cost can be
prohibitive if small sample numbers. Good NPV of
beta-D-glucan and GM (particularly from BAL) can be useful
for stopping empiric therapy.
TDM
Need to have rapid TAT and easy availability. Taking levels in
high income clinical countries is easy with guidance available;
FIGURE 3
Antifungal costs before and after a stewardship intervention
VIEW TDM OF ANTIFUNGAL From: López-Medrano F, San Juan R, Lizasoain M, et al. A non-
AGENTS GUIDELINES compulsory stewardship programme for the management of

antifungals in a university-affiliated hospital. Clin Microbiol Infect. 2013;
19: 56-61.
http://www.clinicalmicrobiologyandinfection.com/article/S1198-
from the British Society for Medical Mycology 743X(14)60309-8/fulltext
However, knowing how to amend doses if levels are outside

therapeutic range is more complex. Voriconazole dose response
Persuasive champions/on ward presence
in adults is non-linear. Small incremental dose increases/
reductions are recommended. Posaconazole has more linear
pharmacokinetics. The newer tablet formulation is associated
with less variability in absorption so should reduce the need for
dose modification and possibly TDM too. TDM for isavuconazole


TOOLKIT RESOURCE
WHAT AFS INITIATIVES HAVE OTHER
GROUPS DONE?
SITE LINK
Apisarnthanarak A, Yatrasert A, Mundy LM;
Thammasat University Antimicrobial Stewardship
Team. Impact of education and an antifungal
stewardship program for candidiasis at a Thai tertiary
care center. Infect Control Hosp Epidemiol. 2010; 31:
722-7
"Continue Key" flickr photo by Got Credit https://flickr.com/photos/ Gouliouris T, Micallef C, Yang H, Aliyu SH,
gotcredit/33716130276 shared under a Creative Commons (BY) license Kildonaviciute K, Enoch DA. Impact of a candidaemia
care bundle on patient care at a large teaching
HOW DO YOU CONTINUE? hospital in England. J Infect. 2016; 72: 501-3
• How do you embed it into practice? López-Medrano F, San Juan R, Lizasoain M, et

Have regular time in job plans with cover for leave. It is also al. A non-compulsory stewardship programme for
possible to get AFS embedded in departments by appointing the management of antifungals in a university-
department champions. In this model the clinical team has affiliated hospital. Clin Microbiol Infect. 2013; 19:
responsibility for AFS and the AFS team advises them. This 56-61
model is similar to that employed in some hospitals for
Micallef C, Aliyu SH, Santos R, Brown NM, Rosembert
infection control and antibacterial stewardships. AFS is
D, Enoch DA Introduction of an antifungal
included in the job plans of clinicians; they are the experts in
stewardship programme targeting high-cost
their fields after all!
antifungals at a tertiary hospital in Cambridge,
• How do you expand? England. J Antimicrob Chemother. 2015; 70: 1908-11
Only expand once the service is up and running and working Standiford HC, Chan S, Tripoli M, et al. Antimicrobial
well. Options include: stewardship at a large tertiary care academic medical
• Increase scope of practice center: cost analysis before, during, and after a
7-year program. Infect Control Hosp Epidemiol. 2012;
• Expand into out-patients 33: 338-45.
• Set up clinics
Valerio M, Rodriguez-Gonzalez CG, Muñoz P. et al.
• Link with other hospitals to do collaborative work Evaluation of antifungal use in a tertiary care
institution: antifungal stewardship urgently needed. J
Antimicrob Chemother. 2014; 69: 1993-9
PDF ARTICLE
Mondain V, Lieutier F, Hasseine L, et al. A 6-year
antifungal stewardship programme in a teaching
hospital. Infection. 2013; 41: 621-8
VIDEOS
Prof Patricia Munoz at Fungal Update 2016
Prof Adilia Warris at Fungal Update 2016
David Denning - BSAC workshop

CHAPTER 22
AUTHOR: SANJAY PATEL
STEWARDSHIP IN PAEDIATRICS
LEARNING OUTCOMES
THE AIM OF THIS On completion of this chapter, the participant should understand:
CHAPTER IS TO:
• The aetiology and duration of symptoms differs considerably between adults and
To explain the reasons why children with respiratory tract infections.
clinicians prescribe antibiotics • It is extremely difficult for clinicians to reliably distinguish bacterial and viral respiratory
to children. tract infections and there are few reliable diagnostic tests available in community based
settings. Unfortunately, this uncertainty often results in clinicians prescribing “just in
To explain the reasons why
case”, despite the availability of good evidence demonstrating that antibiotics make little
parents take their child with
or no difference to the speed of symptoms resolution in most children with bacterial RTIs
fever to see a healthcare
• Decisions about whether to prescribe antibiotics in children with RTIs should be made
professional.
using evidence based guidelines.Inconsistent prescribing practices impact on future
To demonstrate that the health seeking behaviour and antibiotic expectations.
duration and severity of • Discussing antibiotic decisions with parents in terms of severe versus non-severe
symptoms is rarely improved infections is likely to be more effective than an explanation based on
with antibiotics in the distinguishingbacterial and viral infections.
majority of children with • In children with uncomplicated sore throats, ear, sinus and chest infections, the pros
respiratory tract infections. and cons of antibiotics should be discussed with parents before prescribing. Clinicians
and parentsshould consider the relatively small benefits of antibiotics versus the risk
To provide strategies for
of adverse effects, antibiotic resistant infectionsin the future, and the impact on parental
clinicians to better negotiate anxiety and future health seeking behaviour.
antibiotic decisions with
• Parent satisfaction remains high, even when no prescribing or delayed prescribing
parents.
approaches are adopted, as long as parentalconcerns have been addressed during
To provide strategies to the consultation.
effectively steward • Antimicrobial stewardship is an extremely effective way of improving antibiotic
antimicrobial use in prescribing within hospital settings.Although there is currently no standardized measure
hospitalised children. of antibiotic prescribing in children, days of therapy (DOT) is likely to be a useful
measurefor benchmarking
INTRODUCTION
The majority of children with
fever and/or infective symptoms
who are taken by their parents/
carers for a consultation are
looked after by community based
healthcare professionals. This
explains why 80% of paediatric
antibiotic prescribing occurs in
https://www.gov.uk/government/publications/health-
community settings. matters-antimicrobial-resistance/health-matters-
antimicrobial-resistance

CHAPTER 22 - STEWARDSHIP IN PAEDIATRICS
Respiratory tract infections make up more than 50% of these Rates of antibiotic use in children are considerably higher in low-
presentations (Figure 1) and of these, approximately 60% are income income countries:
prescribed antibiotics, although there is good evidence to
suggest that the majority of these children gain little or no
benefit from them.1
FIGURE 1
From Thompson PL et al. ADC 2009
Thompson PL, Spyridis N, Sharland M, Gilbert RE, Saxena S, Long
PF, et al. Changes in clinical indications for community antibiotic
prescribing for children in the UK from 1996 to 2006: will the new
NICE prescribing guidance on upper respiratory tract infections just be
ignored? Arch Dis Child. Antibiotic use in children under 2 years of age from sites in eight
different countries: Dhaka (Bangladesh), Fortaleza (Brazil), Vellore
(India), Bhaktapur (Nepal), Naushahro Feroze (Pakistan), Loreto (Peru),
Young children are the highest recipients of antibiotics (Figure 2) Venda (South Africa) and Haydom (United Republic of Tanzania).
Rogawski TE et al. Bull World Health Organ. 2017 Jan 1; 95(1): 49–61.

TOOLKIT RESOURCE
PDF ARTICLE
Thompson PL, Spyridis N, Sharland M, Gilbert RE,
Saxena S, Long PF, et al. Changes in clinical
indications for community antibiotic prescribing for
children in the UK from 1996 to 2006: will the new
NICE prescribing guidance on upper respiratory tract
infections just be ignored? Arch Dis Child
SITE LINK
FIGURE 2
From: Pottegard A, Broe A, Aabenhus R, Bjerrum L, Hallas J, Damkier Pottegard A, Broe A, Aabenhus R, Bjerrum L, Hallas
P. Use of antibiotics in children: a Danish nationwide drug utilization J, Damkier P. Use of antibiotics in children: a Danish
study. Pediatr Infect Dis J. 2015; 34(2): e16-22 nationwide drug utilization study. Pediatr Infect Dis J.
2015; 34(2): e16-22

This chapter will initially focus on antibiotic prescribing in

community based settings, exploring the drivers for prescribing
and strategies to address these. Antibiotic stewardship
strategies for children with severe infections managed within
hospital settings will then be discussed.
ANTIBIOTIC PRESCRIBING FOR

CHILDREN IN COMMUNITY BASED
SETTING
a) Why do clinicians prescribe antibiotics for children?2
• Perceived vulnerability of children, especially young

children FIGURE 3
• Seeking safety in the face of uncertainty (especially if Rates of invasive pneumococcal disease among children aged <5
years, 1998-2010, USA https://www.cdc.gov/vaccines/pubs/surv-
re-presentation)
manual/chpt11-pneumo.html
- Uncertainty is driven by the difficulty in distinguishing
bacterial and viral infections
- Perceived risk of suppurative complications from an
untreated bacterial respiratory tract infection, especially
in young children
• Repercussions of “missing something” in a child
- The media are inclined to pick up on any cases
where significant morbidity/death in a child has
resulted from a healthcare professional ‘missing’ a
severe infection
- Staff with little experience of seeing unwell children
are less confident at ruling out severe infection
b) Epidemiology of serious infections in children
Streptococcus pneumoniae, Neisseria meningitidis, and

Haemophilus influenza type B are the most common infectious
FIGURE 4
agents responsible for bacterial meningitis and sepsis in
children. The introduction of conjugate vaccines against these
agents has resulted in a marked reduction in their prevalence
in children (Figures 3 to 5, respectively), explaining the significant
reduction in rate of serious infections in children
over recent years.
c) Does the natural history of infections in children and

adults differ?
One of the reasons that parents request antibiotics is the

persistence of symptoms during an infective episode. However,
the natural history of respiratory tract infections differs
considerably between adults and children, with children often
experiencing a considerably longer duration of symptoms
following viral infections. Following a rhinovirus infection, 20%
FIGURE 5
of adults remain symptomatic at 10 days, compared to 73% of
Incidence per 100,000 population of invasive Haemophilus influenzae
children. Cough occurs in 40% of adults, with only 20% still type b (Hib) disease in children aged <5 years, 1980-2012, USA https://
affected by day 10, compared to 70% of children experiencing www.cdc.gov/mmwr/preview/mmwrhtml/rr6301a1.htm

cough, with it persisting at day 10 in over 40%. (Cotton et al. S - They want advice on how to manage their child’s
Afr Fam Pract (2004) . 2008 ; 50(2): 6–12). symptoms
The aetiology of respiratory tract infections also varies markedly

between adults and children. A study of children admitted with
lower respiratory tract infections (RTI) demonstrated that a viral WATCH ANIMATION
cause was responsible in the vast majority (77%). There is even
variation within the paediatric population; RTI in young children
are more likely to be of viral aetiology than in older children. The
prevalence of throat swabs positive for Group A streptococcus is ii) “If a parent expects antibiotics, it is because they think that
far lower in younger children with acute pharyngitis than in older their child has a bacterial infection”
children (Figure 6).
NOT TRUE – parents often feel that antibiotics are required to

treat ‘severe’ infections rather than to treat bacterial infections:3
• parents often believe that features suggesting a

FIGURE 6 severe infection include high fever, prolonged duration
http://pediatrics.aappublications.org/content/pediatrics/126/3/e557. of symptoms and degree of impact on the child
full.pdf Shaikh N, Leonard E, Martin JM. Prevalence of streptococcal
(sleep / school)
pharyngitis and streptococcal carriage in children: a meta-analysis.
Pediatrics. 2010; 126(3): e557-64. • Parents perception of susceptibility also plays a role in
their expectation for antibiotics (younger, underlying
health issues)
d) Common misconceptions
i) “Parents bringing their child to a GP / ED with a fever iii) “Withholding antibiotics simply makes parents re-present
usually expect antibiotics” later / present elsewhere”
NOT TRUE - parents do not generally expect antibiotics when NOT TRUE – not prescribing does not increase the rate of
they seek a consultation:2 representations. Parents are extremely reassured when a shared
decision making approach is used to discuss their child’s illness,
• Parents seek a consultation because:-
even when antibiotics are subsequently not prescribed. If
- It provides a proper ‘health-check’ and in their opinion, anything, parents are less likely to represent during that illness
removes any ‘health-threat’ and are often empowered to self-manage future illnesses.1
• Parents lack confidence to distinguish self-limiting

illnesses from serious ones but believe that clinicians can

iv) “If antibiotics are not prescribed, parents are more likely e) What’s the best way to negotiate antibiotic decisions
to complain” with parents?
NOT TRUE – adopting a shared decision making approach with By assuming that parents expect antibiotics when their child
the parents when managing a child with an infection results in is unwell, there is a risk that this becomes the focus of the
extremely high levels of satisfaction, even when antibiotics are consultation, with the clinician trying to justify their decision not
not prescribed.4 to prescribe antibiotics. This approach also commonly results
in clinicians explaining illness in terms of bacterial and viral
v) “Young children are more susceptible to suppurative infections. Unfortunately, parents rarely seek antibiotics because
complications following a respiratory tract infection than older they think their child has a bacterial illness; instead their opinions
children” about antibiotic need are based on their perception of severity
NOT TRUE – young children have far lower rates of suppurative of illness in their child, including factors such as impaired sleep,
complications than older children, even when antibiotics are not height of fever and prolonged duration of symptoms.3
prescribed:5
• Rate of mastoiditis following otitis media (age 0-4 years

versus 5-15 years): 1.33 vs 2.39 per 10,000
• Rate of quinsy after tonsillitis (age 0-4 years versus 5-15

years): 1.59 vs 5.99 per 10,000
vi) “Children with infected eczema require antibiotic

treatment”
NOT TRUE – Children with skin and soft tissue infections

(SSTI) make up an increasing proportion of patients started on
antibiotics. There is evidence to suggest that oral and topical
antibiotics have no effect (and potentially a harmful effect), on
subjective eczema severity in children with clinically infected
eczema in the community (Figure 7).
A more effective approach to achieving a successful consultation

involves focusing on the reasons the parent sought a
consultation. It is important to reassure the family that although
their child has an infection that is having an impact on their
sleep/feeding, their symptoms are not indicative of a severe
infection in terms of objective parameters / ‘red-flags’. Parents
should also be provided with information about the likely
duration of symptoms and advice on how to manage them. Most
importantly, one must clearly explain the symptoms that parents
should look out for and the actions required if they were to occur.
All this information should ideally be provided both verbally
and in writing. Using such a shared decision making decision
approach results in marked reductions in antibiotic prescribing.4
FIGURE 7
Another effective strategy that can be used in conjunction with
FROM: Francis NA, Ridd MJ, Thomas-Jones E, Shepherd V, Butler the approaches outlined above is the use of delayed prescribing,
CC, Hood K, et al. A randomised placebo-controlled trial of oral where an antibiotic prescription can be collected at the parents’
and topical antibiotics for children with clinically infected eczema in discretion after 72 hours if they feel that their child still not
the community: the ChildRen with Eczema, Antibiotic Management improving. Parents are often extremely reassured when such an
(CREAM) study. Health Technol Assess. 2016; 20(19): i-xxiv, 1-84. https://
approach is adopted and the overall use of antibiotics is reduced
www.journalslibrary.nihr.ac.uk/hta/hta20190/#/abstract
by up to 80% in some studies.1
f) Do all children with bacterial respiratory tract infections

require treatment with antibiotics?

One of the major challenges facing clinicians is distinguishing ii) Tonsillitis

whether a child presenting with an RTI has a bacterial or viral
There is data, albeit limited, to suggest that antibiotics have little
infection. It is often extremely difficult to make this decision
or no impact in reducing the severity of symptoms in the majority
clinically and there are few reliable diagnostic tests that can
of children with acute tonsillitis:
assist in a community based setting. This uncertainty often
results in clinicians prescribing “just in case”. However, there is
an increasing body of evidence to show that antibiotics to do
not significantly reduce severity or duration of symptoms in the
majority of children with RTIs, irrespective of the aetiology: -
i) Acute otitis media (AOM)
A systematic review of 13 RCTs (3401 children and 3938 AOM From Spinks at al: http://onlinelibrary.wiley.com/doi/10.1002/14651858.
episodes) from high-income countries demonstrated that CD000023.pub4/full
antibiotics have no early effect on pain, a slight effect on pain in
Spinks A, Glasziou PP, Del Mar CB. Antibiotics for sore throat.
the days following and only a modest effect on the number of Cochrane Database Syst Rev. 2013; (11): CD000023
children with tympanic perforations, contralateral otitis episodes
and abnormal tympanometry findings at two to four weeks and
iii) Lower respiratory tract infections (LRTIs)
at six to eight weeks compared with placebo. This suggests that
in high-income countries, most cases of AOM spontaneously The lack of evidence around the benefits of antibiotics in
remit without complications. children with LRTIs is suggested by the fact that there is
currently a randomised controlled trial recruiting children
Even in children with AOM under 2 years of age, there is
between 6 months and 12 years of age presenting with an
evidence to suggest that antibiotics make very little difference to
acute uncomplicated lower respiratory infection (LRTI), defined
the severity of symptoms in the majority of children (Figure 8):
as an acute cough as the predominant symptom, judged to be
infective in origin, lasting <21 days. Patients will be randomised
to either an antibiotic arm (amoxicillin) or a placebo arm for 7
days and the primary outcome being evaluated is the duration of
significant symptoms
g) So which children with RTIs should we be treating with

antibiotics?
i) Acute otitis media
Consider starting oral antibiotics only if any of the following

criteria are met in a child presenting with AOM (bulging ear drum
or discharge):-
• Symptoms for 4 days or more
• Purulent discharge from ear canal (not due to otitis

externa)
• Systemically unwell
FIGURE 8
• Under 6 months of age with presumed AOM
Resolution of symptoms in children under 2 years of age with AOM
Hoberman A et al. Treatment of acute otitis media in children under • In children 6 months - 2 years old:-
2 years of age. N Engl J Med. 2011 Jan; 364(2):105-115 Copyright ©
(notice year) Massachusetts Medical Society. Reprinted with permission - Bilateral OM
from Massachusetts Medical Society
- Unilateral OM and symptom score of >8 in children 6
months - 2 years old (0=no symptoms, 1=a little, 2=a lot)
for the following criteria:-
• fever (>39°C = score of 2)
• tugging ears

• crying more unit). Inconsistent prescribing practices impact on health

seeking behaviour and antibiotics expectations during future
• irritability
infective episodes.
• difficulty sleeping
• less playful
• eating less TARGET ANTIBIOTIC WEBINAR

ii) Tonsillitis SERIES - ANTIBIOTICS FOR
Base decision to treat on FeverPAIN score (Fever, Purulence, CHILDREN
Attend within 3 days of onset or less, severely Inflamed tonsils,
No cough or coryza)
WATCH VIDEO
SEE SCORE

TOOLKIT RESOURCE
• score 0-1 = 18% streptococci: use no antibiotics
PDF ARTICLES
• score 2-3: 34-40% streptococci, use back up/delayed
antibiotic Shaikh N, Leonard E, Martin JM. Prevalence of
streptococcal pharyngitis and streptococcal carriage
• score ≥4: 62-65% streptococci, use immediate antibiotic in children: a meta-analysis. Pediatrics. 2010; 126(3):
This score is validated in children aged 3 years and older. e557-64
However, younger children are less likely to have a bacterial
Hoberman A et al. Treatment of acute otitis media
aetiology and are less likely to develop complications.
in children under 2 years of age. N Engl J Med.
iii) LRTIs 2011 Jan; 364(2):105-115 Copyright © (notice year)
Massachusetts Medical Society. Reprinted with
There is a paucity of evidence to guide antibiotic prescribing
permission from Massachusetts Medical Society
decisions in children and most national guidelines tend to focus
on LRTIs in adults. Prior to the results of the ARTIC PC study SITE LINKS
being made available,
https://www.cdc.gov/vaccines/pubs/surv-manual/
chpt11-pneumo.html
VISIT SITE https://www.cdc.gov/mmwr/preview/mmwrhtml/

rr6301a1.htm
Cotton et al. S Afr Fam Pract (2004) . 2008 ;

a pragmatic approach seems most appropriate, with 50(2): 6–12
consideration of antibiotics if persistent/recurrent fever
Francis NA, Ridd MJ, Thomas-Jones E, Shepherd V,
over preceding 24-48 hours with chest wall recession and
Butler CC, Hood K, et al. A randomised placebo-
tachypnoea.
controlled trial of oral and topical antibiotics for
children with clinically infected eczema in the
h) Educational strategies community: the ChildRen with Eczema, Antibiotic
Clinicians should be provided with up to date information on Management (CREAM) study. Health Technol Assess.
antimicrobial stewardship and the management of paediatric 2016; 20(19): i-xxiv, 1-84
infections within robust education programmes. Priority should
be placed on ensuring that consistent management approaches
are adopted across community settings and front of house
hospital settings (emergency department/paediatric assessment

a) Antimicrobial stewardship in hospitalised children

TOOLKIT RESOURCE Although far fewer children receive antibiotics in hospital
settings than in community based settings, the impact of
SITE LINKS injudicious prescribing in hospitals can be catastrophic,
including outbreaks of highly resistant infections resulting in
http://onlinelibrary.wiley.com/doi/10.1002/14651858.
significant mortality and morbidity.
CD000023.pub4/full
Active surveillance of antimicrobial prescribing (antimicrobial
Spinks A, Glasziou PP, Del Mar CB. Antibiotics stewardship) is more easily performed in hospital than in
for sore throat. Cochrane Database Syst Rev. 2013; community based settings. The principles of antimicrobial
(11): CD000023 stewardship (prospective audit with intervention and feedback
Antibiotics for Lower Respiratory Tract Infection in +/- formulary restriction and preauthorisation) apply equally to
Children presenting in Primary Car children as they do to adults (Table 1). In paediatric patients, as in
adults, the successful implementation of stewardship strategies
have a significant impact on reducing overall antimicrobial use,
broad spectrum intravenous antibiotic use, and reducing rates of
ANTIBIOTIC PRESCRIBING FOR resistance, along with delivering substantial cost savings. There
CHILDREN IN HOSPITAL SETTINGS are some unique challenges in paediatrics, however, including
a paucity of data on optimal antimicrobial strategies,7 a relative
Over 35% of paediatric inpatients receive at least one lack of local microbiological data to guide empirical antibiotic
antimicrobial on any given day. An even greater percentage choices and limited human resources available for stewardship
of children are on antimicrobials in tertiary centres. Parenteral activities. Clinical challenges include:
administration is very common in Asia (88%), Latin America
(81%) and Europe (67%) and critically important antibiotics • Severe childhood infection often presenting with non-
for hospital-acquired infections are used more commonly in specific symptoms and signs, especially in infants
neonates than in children (34.9% versus 28.3%). Table 2 outlines and neonates
the most-commonly recorded reasons for prescribing antibiotics • Young infants (<3 months of age) being at considerably
in children and neonates in hospital. 16 A significant proportion higher risk of early and late-onset sepsis due to
of neonates and children are receiving these antimicrobials invasive infection
inappropriately.
• Commonly used investigations such as C-reactive protein
and blood cultures lacking sensitivity in young children
TABLE 2
From Versporten et al: https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkv418 Include link to article in
Toolkit Resource [Versporten A, Bielicki J, Drapier N, Sharland M, Goossens H. The Worldwide Antibiotic Resistance and
Prescribing in European Children (ARPEC) point prevalence survey: developing hospital-quality indicators of antibiotic
prescribing for children. J Antimicrob Chemother. 2016; 71(4): 1106-17.]

From Bielicki et al. PIDJ 2015 http://journals.lww.com/pidj/fulltext/2015/03000/Antimicrobial_Stewardship_for_Neonates_and.29.aspx

Although the majority of hospitals have local prescribing EVALUATING THE QUALITY OF
guidelines for common infections, formal paediatric antimicrobial ANTIBIOTIC PRESCRIBING IN CHILDREN
stewardship remains rather rudimentary in the majority of
Collecting data on antibiotic prescribing allows the quality of
paediatric and neonatal in-patient settings.
prescribing and the effectiveness of stewardship activities to be
i) Children with co-morbidities evaluated. In addition, providing feedback to clinicians about
Children with co-morbidities post challenges in terms of their prescribing is an important way to obtain ‘buy-in’ and is
antimicrobial stewardship: - likely to be an effective driver for sustaining behaviour change.
• their potential for rapid deterioration often results in a However, a major challenge is quantifying the volume of
lower threshold for commencing antibiotics antibiotics prescribed to children. The most commonly used
measure in adults is the defined daily dose (DDD; the assumed
• they are often vulnerable in terms of impaired immunity average maintenance dose per day for a drug used for its main
and the presence of indwelling devices, meaning that indication in adults). Weight variation in children means that
empirical antibiotic choices need to take account of a DDD has a very limited role in accurately quantifying paediatric
wider range of potential pathogens and pathologies antibiotic prescribing and is a poor marker for benchmarking.
• they are more likely to be colonised with resistant Although there is currently no standardized measure of
organisms, which often results in broader spectrum antibiotic prescribing in children, days of therapy (DOT) is likely
antibiotics being used empirically to be a far more useful measure (Figure 9).
ii) Hospital acquired infections Metrics for benchmarking include:
Bloodstream infections account for a particularly high proportion • Total antibiotic use (DOT)
of paediatric hospital acquired infections compared with all • Total parenteral antibiotic use (DOT)
other medical specialities. Not only are clear guidelines required
for the management of these infections, including information • Total oral antibiotic use (DOT)
on the timely removal of central lines, but more importantly, • Broad-spectrum parenteral antibiotic use (DOT)
robust infection control measures must be in place, including
• Combination parenteral antibiotic use (DOT)
central line care bundles to avoid unnecessary exposure to long
courses of IV antibiotics and increased mortality and morbidity. • Total oral antibiotic use in respiratory tract infections (DOT)
• Broad spectrum oral antibiotic use in respiratory tract

infections (DOT)

TOOLKIT RESOURCE • Antibiotic use for surgical prophylaxis (DOT)
SITE LINKS • Antibiotic use for medical prophylaxis (DOT)
Versporten A, Bielicki J, Drapier N, Sharland M,

Goossens H. The Worldwide Antibiotic Resistance
and Prescribing in European Children (ARPEC) point
prevalence survey: developing hospital-quality
indicators of antibiotic prescribing for children. J
Antimicrob Chemother. 2016; 71(4): 1106-17.
Bielicki J, Lundin R, Patel S, Paulus S. Antimicrobial

stewardship for neonates and children: a global
approach. Pediatr Infect Dis J. 2015; 34(3): 311-3.

Child Health Antibacterials

Total Usage and Monthly Spells
3500 2000
1800
3000
1600
2500 1400
1200
2000
1000
1500
800
1000 600
400
500
200
0 0
Jan
Jan
Jun
Jun
Jan
Jun
Jan
Jun
Jan
Jun
Oct
Oct
Oct
Oct
Sep
Sep
Sep
Sep
Mar
Mar
Mar
Mar
Mar
Jul
Feb
Jul
Feb
Jul
Feb
Jul
Feb
Feb
May
Dec
May
Dec
Nov
Dec
Nov
Dec
Nov
Nov
May
May
May
Apr
Apr
Apr
Apr
Apr
Aug
Aug
Aug
Aug
2010 2011 2012 2013 2014
Total treatment days SPELLS
FIGURE 9
Example of paediatric antibiotic surveillance and impact of thrice weekly paediatric stewardship rounds at University Hospitals Southampton, UK
In addition to measuring the quantity of antimicrobial prescribing, Although the collection of high quality data in community
it is important to measure the quality of settings is often challenging, it is essential that metrics on
prescribing, including: antibiotic prescribing in these children are collected in order
to evaluate the impact of community based interventions to
• Documentation of the reason for antimicrobial prescribing
improve prescribing and to facilitate benchmarking between
• Adherence to local prescribing guidelines clinicians and centres.
• Dosing as per local prescribing guidelines
The implementation of a paediatric antimicrobial stewardship

programme over several years at a Children’s hospital in the USA
has been evaluated:
VIEW DOCUMENT

SUMMARY REFERENCES
1. Little P, Gould C, Williamson I, Moore M, Warner G, Dunleavey
The vast majority of paediatric antibiotic prescribing occurs in
J. Pragmatic randomised controlled trial of two prescribing
community settings. Although extremely challenging, focusing
strategies for childhood acute otitis media. BMJ. 2001;
interventions on this cohort of children is likely to have the
322(7282): 336-42.
greatest impact on population level prescribing. However, it
is often difficult to collect high quality prescribing data on this 2. Cabral C, Lucas PJ, Ingram J, Hay AD, Horwood J. "It's safer to
cohort of children and antibiotic stewardship strategies used to ..." parent consulting and clinician antibiotic prescribing
improve antibiotic prescribing in hospital setting are often hard decisions for children with respiratory tract infections: An
to implement in community based settings. Prioritising data analysis across four qualitative studies. Soc Sci Med. 2015;
collection is essential for getting buy-in from clinicians and is 136-137: 156-64.
likely to be an effective driver for behaviour change. 3. Cabral C, Ingram J, Lucas PJ, Redmond NM, Kai J, Hay AD,
et al. Influence of Clinical Communication on Parents'
Antibiotic Expectations for Children With Respiratory Tract
Infections. Ann Fam Med. 2016; 14(2): 141-7.
4. Francis NA, Butler CC, Hood K, Simpson S, Wood F, Nuttall J.
Effect of using an interactive booklet about childhood
respiratory tract infections in primary care consultations on
reconsulting and antibiotic prescribing: a cluster randomised
controlled trial. BMJ. 2009; 339: b2885.
5. Petersen I, Johnson AM, Islam A, Duckworth G, Livermore
DM, Hayward AC. Protective effect of antibiotics against
serious complications of common respiratory tract infections:
retrospective cohort study with the UK General Practice
Research Database. BMJ. 2007; 335(7627): 982.
6. Venekamp RP, Sanders SL, Glasziou PP, Del Mar CB, Rovers
MM. Antibiotics for acute otitis media in children. Cochrane
Database Syst Rev. 2015; (6): CD000219.
7. McMullan BJ, Andresen D, Blyth CC, Avent ML, Bowen AC,
Britton PN, et al. Antibiotic duration and timing of the switch
from intravenous to oral route for bacterial infections in
children: systematic review and guidelines. Lancet Infect Dis.
2016; 16(8): e139-52.

CHAPTER 23
AUTHOR: PRIYA NORI
ANTIMICROBIAL
STEWARDSHIP AND OPAT
LEARNING OUTCOMES
CHAPTER IS TO:
• Describe key elements of a multi-disciplinary OPAT bundle
To describe the core elements • Outline distinct models of OPAT care delivery
of OPAT care bundles and their
• Describe unique challenges to OPAT in different parts of the world
relationship to antimicrobial
atewardship. • List examples of challenges central to the OPAT-stewardship dilemma, such as antibiotic
spectrum versus convenience of dosing
To define distinct models of
OPAT delivery and their ideal
settings.
To identify potential conflicts CLINICAL VIGNETTE:

between core stewardship
principles and feasibility of
OPAT. A 75-YEAR-OLD FEMALE WITH HISTORY OF OBESITY
AND DIABETES IS ADMITTED TO THE HOSPITAL WITH
To highlight the individual
roles of the stewardship
3 WEEKS OF RIGHT KNEE PAIN, SWELLING, AND
pharmacist and physician WARMTH. SHE HAS HISTORY OF PRIOR BILATERAL
in improving OPAT care. TOTAL KNEE ARTHROPLASTY 10 YEARS AGO. PHYSICAL
To identify unique challenges
EXAM REVEALS DEHISCENCE OF PRIOR SURGICAL
to OPAT in various countries. WOUND WITH PURULENT DRAINAGE. SHE UNDERGOES
DEBRIDEMENT OF RIGHT KNEE INFECTION WITH
EXPLANT OF OLD PROSTHESIS AND PLACEMENT OF
AN ANTIBIOTIC IMPREGNATED SPACER. SYNOVIAL
TISSUE CULTURES REVEAL METHICILLIN SUSCEPTIBLE
STAPHYLOCOCCUS AUREUS. SHE IS TREATED WITH
IV CEFAZOLIN 2G EVERY 8 HOURS INITIALLY, THEN
DISCHARGED HOME ON IV CEFTRIAXONE 2G DAILY
TO COMPLETE A 6-WEEK COURSE

CHAPTER 23 - ANTIMICROBIAL STEWARDSHIP AND OPAT
INTRODUCTION Several of the proposed bundle elements align with the

expertise of antimicrobial stewardship programs and represent
Outpatient parenteral antibiotic therapy (OPAT) is a well-
core stewardship functions discussed in chapters 2 and 3
established, cost-effective solution to prolonged hospitalisation
(see figure 2):
for management of complex infections1. The goal of OPAT is
the provision of high quality anti-infective therapy accessible 1 Initial selection of the appropriate antimicrobial regimen
across a multitude of patient care settings. Over 3 decades for a given indication, dose, route, and projected treatment
of North American and European OPAT experience attests duration by the infectious diseases (ID) consultative service
to the success and sustainability of OPAT programs2,3. Care (clinicians and pharmacists)
of OPAT patients is a coordinated, multidisciplinary effort at 2 Monitoring for clinical response, antimicrobial tolerability,
each stage: 1) initial presentation to the acute care setting, 2) and adjustment of regimens based on alterations in laboratory
inpatient convalescence, 3) transition of care to home or skilled parameters
nursing facility, and finally, 4) post-acute care by the OPAT
team4. Reductions in hospital lengths of stay, readmission rates, 3 Selection of the most appropriate, tolerable, and feasible
antibiotic utilisation, and optimisation of patient outcomes are discharge regimen considering factors such as antimicrobial
goals central to OPAT, hospital administration, and antimicrobial cost, drug stability in the outpatient setting, and compatibility
stewardship. with selected IV access
In 2013, Muldoon et al. proposed a bundle of OPAT program 4 Appropriateness and timing of IV to PO switch considering
best practices including appropriate patient selection, infectious penetration at the site of infection 5.
diseases consultation, patient/caregiver education, discharge 5 Education and counselling on risk factors for infection
planning, outpatient monitoring/tracking, and a program recurrence, infection prevention, and treatment goals and
outcomes review for quality assurance5 expectations 4,6.
APPROPRIATE
PATIENT SELECTION
PROGRAM OUTCOMES INFECTIOUS DISEASES

REVIEW CONSULTATION
OUTPATIENT PATIENT/CAREGIVER
MONITORING EDUCATION
DISCHARGE
PLANNING
FIGURE 1
OPAT Bundle for Patient Care Optimisation5

6 Input on cessation of antibiotics at clinical cure or clinical failure, if the later is due to
surgical disease such as retained prosthesis or necrotic bone
TOOLKIT

RESOURCE IV
intravenous route 1 SELECTION
E.g.: IV Cefazolin 2g, 2g, 3g for invasive MSSA infection in a
MSSA hemodialysis patient without other IV access
Methicillin susceptible
SITE LINK Staphylococcus
aureus

Financial impact of
a home intravenous
PICC
peripherally inserted
central venous
2 MONITORING
E.g.: Weekly monitoring of vancomycin troughs with dose
catheter adjustment as needed
antibiotic program on
PO
a medicare managed oral route
care program. MRSA
Methicillin resistant
3 FEASIBILITY
E.g.: PICC preferred to midline catheter for IV antibiotic
Staphylococcus courses >30 days
Good practice aureus
recommendations for
outpatient parenteral 4 IV TO PO SWITCH
E.g.: Switch from IV vancomycin to PO clindamycin
antimicrobial therapy for MRSA osteomyelitis
(OPAT) in adults in the
UK: a consensus
statement 5 COUNSELING
E.g.: Education on modifiable risk factors
(hyperglycemia, smoking, obesity, etc.)
Practice guidelines

for outpatient parenteral
antimicrobial therapy.
6 STOPPING THERAPY
E.g.: When further antibiotics are ineffective without
amputation for gangrene
IDSA guidelines
FIGURE 2
Continuum of Stewardship Core Activities within OPAT Programs
Bundle in the Bronx:
Impact of a Transition-
of-Care Outpatient
TRANSITIONS OF CARE FROM ACUTE TO POST-ACUTE
Parenteral Antibiotic
OPAT CARE SETTINGS
Therapy Bundle
on All-Cause 30-Day A transition-of-care OPAT service coordinating both inpatient and outpatient aspects of
Hospital Readmissions management may potentially impact outcomes and processes of care. In 2013, Keller
and colleagues reported results of a controlled, quasi-experimental study of a newly
Are we ready for implemented infectious diseases transition service (IDTS) for OPAT patients discharged
an outpatient parenteral from the Hospital of the University of Pennsylvania, most of whom received OPAT from
antimicrobial therapy a home health agency. Primary outcomes included readmissions and ED visits within
bundle? A critical 60 days of discharge, while secondary outcomes included process of care measures
appraisal of the (e.g. antimicrobial therapy errors, laboratory test receipt, outpatient follow-up) and
evidence non-readmission clinical outcomes (mortality within 60 days of discharge, Clostridium
difficile infections, adverse antimicrobial events, and catheter complications). After
Outpatient parenteral adjusting for covariates, no significant difference in primary outcome was observed
antimicrobial therapy between intervention arm and control arm patients (adjusted odds ration [OR] = 0.48;
and antimicrobial 95% CI 0.13-1.79), however, implementation of the IDTS was associated with fewer
stewardship: challenges antimicrobial therapy errors (OR = 0.062; 95% CI = 0.015-0.262) increased laboratory test
and checklists receipt (OR 27.85; 95% CI 12.93-59.99), an improved outpatient follow-up (OR = 2.44;
95% CI 1.50-3.97). A significant difference in use of penicillins and cephalosporins was
observed between intervention and control arm patients, but the impact of this difference
on outcomes is not known (together, these drug classes accounted for over 50% of
antimicrobials used in the study)7.

OPAT PATIENT DIVERSITY AND DISTINCT

OPAT CARE MODELS
TOOLKIT RESOURCE
OPAT patients share comorbidities (diabetes mellitus, chronic
kidney dysfunction, vascular disease, etc.), and all require
SITE LINKS
extended antibiotic courses for moderate to severe, often 7. The Impact of an Infectious Diseases Transition
chronic or recurrent infections4. However, they hail from Service on the Care of Outpatients on Parenteral
diverse socioeconomic backgrounds and geographic settings Antimicrobial Therapy
(e.g. urban versus suburban or rural populations; community
8. https://www.medicare.gov/part-d/coverage/part-d-
residents versus skilled nursing or long term care residents).
coverage.html. Accessed July 1, 2017
Variable health insurance coverage of costly antimicrobials and
skilled nursing services is challenge unique to OPAT patients 9. https://www.drugs.com/price-guide/daptomycin.
in countries with a substantial mix of private and government Accessed July 1, 2017
insurance plans. These factors may influence the selection of 10.Developments in outpatient parenteral
the OPAT regimen by the ID consultative team. Upon transition antimicrobial therapy (OPAT) for Gram-positive
of patient care to the post-acute care setting, home infusion infections in Europe, and the potential impact
therapy versus placement in a skilled nursing facility for receipt of daptomycin
of OPAT is also influenced by insurance coverage, patient
functional status and need for additional skilled nursing services.
In all models, infectious diseases specialists serve as OPAT
In the United States, Medicare part D may cover the cost leaders coordinating patient care and clinically monitoring
of intravenous (IV) antibiotics but may not cover infusion- patients at outpatient follow up visits. However, comprehensive
related nursing services and supplies associated with in home OPAT management (patient outreach, IV access care, monitoring
administration of OPAT8. For instance, while generic daptomycin of labs, education, and counseling) is multidisciplinary endeavor
has been available in the United States since 2016, extended of trained nurses, pharmacists, and outreach coordinators4.
courses utilised in the treatment of complex or refractory Ambulatory infusion centres are best suited to populous urban
methicillin resistant Staphylococcus aureus (MRSA) infections areas where patients are not required to travel far distances for
are associated with a significant cost, with a 500mg vial costing their infusions, and OPAT programs are financially sustainable
roughly $360 to $382 USD9. Therefore, OPAT utilisation due to high patient volume and revenue generated11.
of daptomycin remains limited, especially in economically
disadvantaged areas of the US. However, in the UK, there are In rural or remote regions, home infusion therapy may be
multiple reports of successful daptomycin use for OPAT, perhaps preferred due to patient convenience and distance from
due to fewer financial barriers, ease of administration, and infusion clinics. For instance, in Canada, the prevalence of
patient tolerance (once daily dosing and short infusion times)10. existing OPAT programs is not well understood, but availability
of OPAT services varies based on province, geography, and
access to clinics12.
DISTINCT OPAT MODELS

CAN BE INDIVIDUALISED TOOLKIT RESOURCE
TO AVAILABLE RESOURCES,
PATIENT DEMOGRAPHICS, SITE LINKS
GEOGRAPHY, AND ACCESS A 1-year retrospective review of outcomes of an informal
TO SPECIALTY SERVICES: OPAT program in Toronto identified readmissions and
repeat emergency department visits in nearly 50% of
• Centralised OPAT at ambulatory infusion centers patients. This lead to the allocation of resources for a
(office or hospital-based) coordinated and structured OPAT program
• Home-based OPAT via licensed infusion and skilled
11. Legal and Reimbursment Issues in OPAT. IDSA
nursing agencies, or
OPAT-ehandbook
• OPAT within skilled nursing facilities
12.Patient Characteristics and Outcomes
PDF ARTICLE of Outpatient Parenteral Antimicrobial Therapy:
A Retrospective Study

AMBULATORY HOME INFUSION BY SKILLED

INFUSION PATIENT, CAREGIVER NURSING
CENTER OR NURSE FACILITY
Pros:
Pros: Pros:
Well-monitored setting Patient independence Well-monitored setting with
additional therapeutic
Staff on site to troubleshoot Comfortable setting
services (physical therapy,
problems
Regular nursing visits to wound care, etc.)
Clinical care and infusion monitor and troubleshoot
Feasible in rural, urban,
therapy centralised problems
or suburban settings
Cons: Feasible in rural settings
On site physician visits
More feasible in urban or Cons: and nursing care
suburban settings
Regular physician visits Success less dependent
Success relies on patient necessary on patient adherence
adherence to visits
Success relies on high- Cons:
functioning patient or
Loss of independence
caregiver and adherence to
treatment plan Unfamiliar setting
FIGURE 3
Pros and Cons of Distinct OPAT Models
THE PHYSICIAN STEWARD AND OPAT

CARE IN THE UNDERSERVED A PREDICTION MODEL FOR 30-DAY HOSPITAL
READMISSIONS IN OPAT PATIENTS INCLUDES
Like other urban centers, New York City (NYC) presents a
AGE (ODDS RATIO [OR], 1.09 PER DECADE;
unique opportunity for OPAT given that patients are often 95% CONFIDENCE INTERVAL [CI] 0.99-1.210),
medically complex, socioeconomically disadvantaged, or AMINOGLYCOSIDE USE (OR, 2.33; 95% CI 1.17-4.57)
have limited functional status requiring intensive nursing care. RESISTANT ORGANISMS (OR, 1.57; 95% CI 1.03-2.36),
Antimicrobial stewardship (selection of the most tolerable and AND NUMBER OF PRIOR HOSPITAL DISCHARGES IN
THE PAST 12 MONTHS WITHOUT IV ANTIBIOTICS (OR,
narrow-spectrum OPAT regimen for the appropriate duration),
1.2 PER PRIOR ADMISSION; 95% CI 1.09-1.32).
stewardship of microbiologic testing and resource allocation
is of particular concern in this setting. With the emergence of • 26% (207/782) of OPAT patients were readmitted
rapid molecular diagnostics in microbiology such as MALDI- within 30 days consistent with prior studies.
ToF, the role of stewardship has expanded to ensure that • 8% of readmitted patients and 4% of non-readmitted
new technologies function to preserve rather than consume patients were prescribed aminoglycosides at initial
healthcare resources and meaningfully impact patient care13. discharge (p=0.03)
Despite well-coordinated OPAT, emergency department (ED) • The study highlights the importance of stewardship in
utilisation and readmissions resulting in repeated microbiologic the selection of alternative, safer OPAT regimens
testing, repeated antibiotic courses for treatment failures and
infection recurrences remain problematic in OPAT patients14-16 PDF ARTICLE

which is best achieved by harnessing local champions and

identifying local incentives and needs20.
TOOLKIT RESOURCE
SITE LINKS OPAT-STEWARDSHIP DILEMMA
13. Implementation of Rapid Molecular Infectious While OPAT programs have emerged across myriad settings,
Disease Diagnostics: The Role of Diagnostic and promotion of judicious antimicrobial use through stewardship
Antimicrobial Stewardship is now embedded in regulatory standards for healthcare
accreditation in the United States21. Often, targeted antibiotic
14. Patients with prosthetic joint infection on IV selection for a given infection may conflict with practical aspects
antibiotics are at high risk for readmission of OPAT care, including convenience and feasibility of long term
treatment. “Collateral damage” of OPAT may include emergence
15. Association of laboratory test result availability of drug resistance, development of healthcare associated
and re-hospitalizations in an outpatient parenteral infections such as Clostridium difficile, and antibiotic associated
antimicrobial therapy programme toxicities. Thus the “antimicrobial stewardship-OPAT dilemma”
described by Gilchrist and colleagues referring to the critical
16. Predictors of hospital readmission in patients
balance of prolonged antibiotic therapy with antibiotic adverse
receiving outpatient parenteral antimicrobial
effects6 as shown in Figure 4.
therapy. Pharmacotherapy
COMMON OPAT-STEWARDSHIP CHALLENGES:

ED utilisation is frequent in disadvantaged settings, particularly 1) LACK OF PUBLISHED DRUG STABILITY DATA
in the Bronx, where approximately 30% of its 1.4 million residents FOR CERTAIN NARROW SPECTRUM AGENTS,
live below the federal poverty level17,18. Without coordinated care, 2) LACK OF NARROW-SPECTRUM AGENTS
such patients discharged on long-term IV antibiotics experience WITH CONVENIENT DOSING SCHEDULES, 3)
loss to follow up and treatment failures. Poor outcomes in LONG INFUSION TIMES FOR CERTAIN AGENTS
patients discharged on IV antibiotics from the Montefiore (E.G. IV VANCOMYCIN), 4) OVERLY BROAD
Health System in the Bronx, NY catalysed the development of SPECTRUM COVERAGE OF AVAILABLE
a transition-of-care OPAT program in 2015. A nurse coordinator ONCE-DAILY AGENTS (E.G. CEFTRIAXONE,
was essential to patient outreach, appointment reminders, and DAPTOMYCIN, ERTAPENEM, ETC.)
trouble shooting of patient concerns by phone. Infusion services
were provided to patients at home by licensed pharmacy and PDF ARTICLE
nursing agencies, or at skilled nursing facilities. OPAT physicians
served as antimicrobial stewards by reviewing weekly laboratory
results and contacting infusion teams and skilled nursing staff
with necessary therapeutic adjustments (e.g. drug level-based
vancomycin dose adjustment for MRSA infections). Compared to TOOLKIT RESOURCE
the prior standard care, patients enrolled in the Montefiore OPAT
program after 2015 had significantly lower 30-day readmissions
SITE LINKS
(13.0% vs. 26.1%, P < .01)4 17. Quick Facts Bronx County, New York. United
States Census Bureau, 2010–2015.
OPAT in Asia represents another potentially unharnessed
opportunity to improve the care of underserved populations.
18. Research, Statistics, Data & Systems. Centers
A 2017 study by Fisher and colleagues sought to characterize
for Medicaid and Medicare Services. 2013.
OPAT in Asia, a setting not previously well described. They
surveyed 171 different healthcare facilities in 17 Asian countries, 19. Medicaid Regional Data Compendium. The
including India, Singapore, China, Japan, and Australia. Medicaid Institute at United Hospital Fund. 2014.
Interestingly, 57% of facilities administer OPAT but only 3%
of facilities outside of Singapore reported comprehensive 20. Outpatient parenteral antibiotic therapy (OPAT)
OPAT services overseen by specialists. Coordinated efforts in Asia: missing an opportunity
to standardize “unchecked” OPAT in Asia is a priority of the
international Infectious Diseases and Stewardship community,


SITE LINKS SITE LINKS
21. New Societal Approaches to Empowering 22. David G. Armstrong, Andrew J.M. Boulton, and
Antibiotic Stewardship Sicco A. Diabetic Foot Ulcers and Their
Recurrence. N Engl J Med 2017; 376:2367-2375.
June 15, 2017DOI
23. Microbiology of diabetic foot infections: from

IN A STUDY OF 1212 UNIQUE EPISODES OF Louis Pasteur to “crime scene investigation.”
DIABETIC FOOT ULCER, MRSA INFECTIONS
ACCOUNTED FOR 57% OF ALL INVASIVE 24. Systemic Antibiotic Therapy for Chronic
INFECTIONS AND WERE ASSOCIATED WITH Osteomyelitis in Adults
INCREASED MORTALITY RISK (HAZARD
RATIO 1.987; 95% CI 1.106-3.568) (CHEN SY ET
AL. INVASIVE SYSTEMIC INFECTION AFTER
HOSPITAL TREATMENT FOR DIABETIC FOOT Osteomyelitis associated with chronic diabetic foot ulcers is
ULCER: RISK OF OCCURRENCE AND EFFECT often polymicrobial (Staphylococcus aureus, Streptococci,
ON SURVIVAL. CLIN INFECT DIS. 2017; 64 (3): Pseudomonas, Enterobacteriaceae, anaerobes, skin flora,
326-334. DOI: 10.1093/CID/CIW736.) yeast, etc.)24. Selection of targeted antibiotic regimens for
diabetic osteomyelitis feasibly administered for 4-6 weeks is
PDF ARTICLE challenging. Since several oral antibiotic classes achieve bone
levels exceeding minimum inhibitory concentrations (MICs)
of pathogens, prolonged courses of oral agents alone or in
combination represents a viable and cost saving alternative
A frequent indication for OPAT is the costly diabetic foot infection
to OPAT, avoiding the need for durable IV access25. Use of
complicated by devascularised bone and osteomyelitis. Patients
outpatient oral regimens with high bioavailability can potentially
with uncontrolled diabetes frequently have underlying vascular
avert hospital admissions unless treatment failures occur with
disease and renal dysfunction, which affects antibiotic dosing and
optimal oral therapy.
route of administration. These comorbidities complicate wound
healing and predispose to recurrent infection22;23. In addition,
site invasive systemic infection cause significant morbidity and
mortality even after initial hospitalization and treatment.
MOST STREAMLINED COST OF ONCE-DAILY

NARROW-SPECTRUM IV-REGIMENS COMPARED
REGIMEN WITH NARROWER AGENTS
PATIENT CONVENIENCE POLYMICROBIAL INFECTIONS,

TOLERANCE, LONG-TERM UNFAVORABLE HOST FACTORS
FEASIBILITY (E.G. DIABETIC FOOT INFECTION)
SUITABILITY OF IV DRUG RESISTANCE

TO PO SWITCH & C diff
SUCCESSFUL
OPAT
FIGURE 4 OUTCOMES
Stewardship-OPAT Dilemma

EXPANDED ROLE OF THE STEWARDSHIP namely, IV to PO switch, protocols for laboratory monitoring
PHARMACIST IN OPAT and reporting of adverse antimicrobial events, and tracking of
antimicrobial resistance data6. An antimicrobial stewardship
The 2012 UK consensus guidelines on OPAT best practices
pharmacist has the training and expertise to assume leadership
endorse the clinical antimicrobial pharmacist as a potential
of these functions, while the physician and nursing leaders
co-director of a comprehensive OPAT team2. Several
coordinate OPAT patient clinical care.
fundamental stewardship principles are incorporated into
the proposed OPAT-stewardship framework of Gilchrist et al.,
1 2 3 4 5
SELECTION OF SELECTION OF DEVELOPMENT OF DEVELOPMENT PRE- AND POST
APPROPRIATE REGIMEN/DOSE/ LAB MONITORING OF AN OPAT DISCHARGE
PATIENT FOR ROUTE PER GIVEN AND INFUSION MEDICATION EDUCATION
OPAT INCLUSION INDICATION PROTOCOLS RECONCILIATION ON CARE PLAN
FORM AND POTENTIAL
ADVERSE EFFECTS
FIGURE 5
Expanded Stewardship Pharmacist Role in OPAT
A PHARMACIST-LEAD OPAT SERVICE

AT A 316-BED SAFETY NET HOSPITAL
TOOLKIT RESOURCE
IN INDIANA PROVIDES OPAT CARE TO SITE LINKS

UNINSURED OR UNDERINSURED PATIENTS. 25. European Surveillance of Antimicrobial
PRIOR TO PROGRAM IMPLEMENTATION IN Consumption (ESAC): Outpatient Parenteral
2008 SEVERAL DEVIATIONS FROM OPAT Antibiotic Treatment in Europe
STANDARDS OF CARE WERE NOTED. AFTER
IMPLEMENTATION, CLINICAL CURE AT THE
END OF TREATMENT WAS OBSERVED IN 93%
OF PATIENTS. AUTHORS CONCLUDED THAT
A PHARMACY-DRIVEN OPAT INTERVENTION
IS SAFE, EFFECTIVE, AND ADAPTABLE TO
OTHER SETTINGS
PDF ARTICLE

Several antibiotic classes with good oral bioavailability can

achieve tissue levels exceeding pathogen MICs. A 2012 review A 2009 COCHRANE REVIEW DID NOT DEMONSTRATE A
of antibiotic therapy for chronic osteomyelitis reported that CLEAR BENEFIT OF IV VERSUS PO THERAPY, AND IDSA
fluoroquinolones, linezolid, fosfomycin, and trimethoprim- PROSTHETIC JOINT INFECTION GUIDELINES SUGGEST
sulfamethoxazole achieve bone concentrations at approximately THAT HIGHLY BIOAVAILABLE ORAL ANTIBIOTICS MAY
50% of serum, and metronidazole penetrates bone at BE AN APPROPRIATE ALTERNATIVE TO PROLONGED
IV THERAPY. THE OVIVA NON-INFERIORITY 5-YEAR
concentrations approximating those in serum. Both doxycycline
TRIAL WILL ULTIMATELY REPORT RESULTS OF 1054
and clindamycin are viable oral options for MRSA osteomyelitis PATIENTS RANDOMIZED TO 6 WEEKS OF ORAL
but doxycycline has variable bone concentrations depending VERSUS IV THERAPY FOR TREATMENT OF BONE AND
on site. Rifampin also demonstrates bone concentrations JOINT INFECTIONS IN THE UK (CONTERNO LO ET AL.
approximating those in serum and is suggested for combination ANTIBIOTICS FOR TREATING CHRONIC OSTEOMYELITIS
IN ADULTS. COCHRANE DATABASE SYST REV. 2009;
therapy particularly in the setting of infected prostheses. At this
8(3):CD004439
time, superiority of bactericidal versus bacteriostatic treatment
of osteomyelitis remains uncertain24. PDF ARTICLE
CONCLUSION
OPAT and antimicrobial stewardship are unified by the mutual
objective of selecting the most effective, well tolerated, and OSMON DR, ET AL. DIAGNOSIS AND
streamlined regimen individualized to the host and site of MANAGEMENT OF PROSTHETIC JOINT
infection. Often pathogen-directed once daily regimens are INFECTION: CLINICAL PRACTICE GUIDELINES
appropriate for OPAT (e.g. IV vancomycin for an invasive BY THE INFECTIOUS DISEASES SOCIETY OF
MRSA infection in an elderly patient). At other times, once daily AMERICA. CLIN INFECT DIS. 2013;56(1):E1–25.;
regimens are prescribed preferentially due to convenience LI, HK ET AL.
of dosing and likelihood of patient adherence to prolonged
antibiotic courses. In the later case, regimens may be too broad PDF ARTICLE
for a given indication (e.g. once daily ertapenem for an intra-
abdominal infection with a susceptible strain of Enterobacter).
An OPAT program design adapted from an antimicrobial

stewardship paradigm can ensure appropriate selection of ORAL VERSUS INTRAVENOUS ANTIBIOTIC
long-term antibiotic regimens, dose adjustments per renal and TREATMENT FOR BONE AND JOINT
hepatic function, therapeutic drug monitoring, and ongoing INFECTIONS (OVIVA): STUDY PROTOCOL FOR
patient education and counseling on risk factor mitigation, A RANDOMISED CONTROLLED TRIAL. TRIALS.
infection prevention, and expected treatment outcomes. 2015; 16: 583. DOI: 10.1186/S13063-015-1098-Y)
Antimicrobial stewards (pharmacists and physicians) are integral
to the multidisciplinary OPAT team. Mounting evidence in favor PDF ARTICLE
of oral antibiotic therapy for bone and joint infections supports
early stewardship intervention, including IV to PO conversion
and potential de-escalation from empiric broad-spectrum IV
therapy to targeted PO therapy.

FIGURE 6
European Surveillance of Antimicrobial
Consumption, OPAT Distribution,
200625
References:
1. Dalovisio JR, Juneau J, Baumgarten K, Kateiva J. Financial impact of a home intravenous antibiotic program on a medicare
managed care program. Clin Infect Dis. 2000; 30:639–42. https://academic.oup.com/cid/article/30/4/639/419485
2. Ann L. N. Chapman, R. Andrew Seaton, Mike A. Cooper, Sara Hedderwick, Vicky Goodall, Corienne Reed, Frances Sanderson,
Dilip Nathwani, on behalf of the BSAC/BIA OPAT Project Good Practice Recommendations Working Group; Good practice
recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a consensus statement. J Antimicrob
Chemother 2012; 67 (5): 1053-1062. doi: 10.1093/jac/dks003 https://academic.oup.com/jac/article/67/5/1053/979985
3. Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect
Dis.2004; 38:1651–72. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/OPAT.pdf
4. Theresa Madaline, Priya Nori, Wenzhu Mowrey, Elisabeth Zukowski, Shruti Gohil, Uzma Sarwar, Gregory Weston, Riganni Urrely,
Matthew Palombelli, Vinnie Frank Pierino, Vanessa Parsons, Amy Ehrlich, Belinda Ostrowsky, Marilou Corpuz, Liise-anne Pirofski;
Bundle in the Bronx: Impact of a Transition-of-Care Outpatient Parenteral Antibiotic Therapy Bundle on All-Cause 30-Day
Hospital Readmissions. Open Forum Infect Dis 2017; 4 (2): ofx097. doi: 10.1093/ofid/ofx097 https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC5570156/pdf/ofx097.pdf
5. Muldoon EG, Snydman DR, Penland EC, Allison GM. Are we ready for an outpatient parenteral antimicrobial therapy bundle? A
critical appraisal of the evidence. Clin Infect Dis. 2013; 57:419–24. https://academic.oup.com/cid/article/57/3/419/460002
6. Gilchrist M, Seaton RA. Outpatient parenteral antimicrobial therapy and antimicrobial stewardship: challenges and checklists.
J Antimicrob Chemother. 2015. Apr;70(4):965-70. doi: 10.1093/jac/dku517. Epub 2014 Dec 23. https://academic.oup.com/jac/
article/70/4/965/806426

References:
1. Dalovisio JR, Juneau J, Baumgarten K, Kateiva J. Financial impact of a home intravenous antibiotic program on a medicare
managed care program. Clin Infect Dis. 2000; 30:639–42. https://academic.oup.com/cid/article/30/4/639/419485
2. Ann L. N. Chapman, R. Andrew Seaton, Mike A. Cooper, Sara Hedderwick, Vicky Goodall, Corienne Reed, Frances Sanderson,
Dilip Nathwani, on behalf of the BSAC/BIA OPAT Project Good Practice Recommendations Working Group; Good practice
recommendations for outpatient parenteral antimicrobial therapy (OPAT) in adults in the UK: a consensus statement. J Antimicrob
Chemother 2012; 67 (5): 1053-1062. doi: 10.1093/jac/dks003 https://academic.oup.com/jac/article/67/5/1053/979985
3. Tice AD, Rehm SJ, Dalovisio JR, et al. Practice guidelines for outpatient parenteral antimicrobial therapy. IDSA guidelines. Clin Infect
Dis.2004; 38:1651–72. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_Library/OPAT.pdf
4. Theresa Madaline, Priya Nori, Wenzhu Mowrey, Elisabeth Zukowski, Shruti Gohil, Uzma Sarwar, Gregory Weston, Riganni Urrely,
Matthew Palombelli, Vinnie Frank Pierino, Vanessa Parsons, Amy Ehrlich, Belinda Ostrowsky, Marilou Corpuz, Liise-anne Pirofski;
Bundle in the Bronx: Impact of a Transition-of-Care Outpatient Parenteral Antibiotic Therapy Bundle on All-Cause 30-Day
Hospital Readmissions. Open Forum Infect Dis 2017; 4 (2): ofx097. doi: 10.1093/ofid/ofx097 https://www.ncbi.nlm.nih.gov/pmc/
articles/PMC5570156/pdf/ofx097.pdf
5. Muldoon EG, Snydman DR, Penland EC, Allison GM. Are we ready for an outpatient parenteral antimicrobial therapy bundle? A
critical appraisal of the evidence. Clin Infect Dis. 2013; 57:419–24. https://academic.oup.com/cid/article/57/3/419/460002
6. Gilchrist M, Seaton RA. Outpatient parenteral antimicrobial therapy and antimicrobial stewardship: challenges and checklists.
J Antimicrob Chemother. 2015. Apr;70(4):965-70. doi: 10.1093/jac/dku517. Epub 2014 Dec 23. https://academic.oup.com/jac/
article/70/4/965/806426
7. Keller SC, Ciuffetelli D, Bilker W, et al. The Impact of an Infectious Diseases Transition Service on the Care of Outpatients on
Parenteral Antimicrobial Therapy. The Journal of pharmacy technology : jPT : official publication of the Association of Pharmacy
Technicians. 2013;29(5):205-214. doi:10.1177/8755122513500922. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4301302/pdf/
nihms633872.pdf
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potential impact of daptomycin. J Antimicrob Chemother 2009; 64 (3): 447-453. doi: 10.1093/jac/dkp245 https://academic.oup.com/
jac/article/64/3/447/776518
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http://www.idsociety.org/opat-ehandbook
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The Canadian Journal of Infectious Diseases & Medical Microbiology;2016:8435257. doi:10.1155/2016/8435257
http://www.ivteam.com/intravenous-literature/opat-patient-characteristics-and-outcomes-described-in-this-article/
13. Kevin Messacar, Sarah K Parker, James K Todd, Samuel R Dominguez . Implementation of Rapid Molecular Infectious Disease
Diagnostics: The Role of Diagnostic and Antimicrobial Stewardship. J Clin Microbiol 55 (3), 715-723. 2017 Feb 22. https://www.ncbi.
nlm.nih.gov/pmc/articles/PMC5328439/pdf/zjm715.pdf
14. Duggal A, Barsoum W, Schmitt SK. Patients with prosthetic joint infection on IV antibiotics are at high risk for readmission. Clin
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parenteral antimicrobial therapy programme. J Antimicrob Chemother. 2014; 69:228–33.
16. Means L, Bleasdale S, Sikka M, Gross AE. Predictors of hospital readmission in patients receiving outpatient parenteral
antimicrobial therapy. Pharmacotherapy. 2016; 36:934–9. Abstract only - http://onlinelibrary.wiley.com/doi/10.1002/phar.1799/
abstract;jsessionid=27D6A1764E3C0DFCE7ED8C585EB7F9E6.
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table/PST045215/36005.
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Research-Statistics-Data-and-Systems/Research-Statistics-Data-and-Systems.html.
19. Medicaid Regional Data Compendium. The Medicaid Institute at United Hospital Fund. 2014. Available at: http://www.

CHAPTER 24
AUTHOR: KARIN THURSKY & ARJUN RAJKHOWA
THE USE OF INFORMATION

TECHNOLOGY TO
SUPPORT ANTIMICROBIAL
STEWARDSHIP
LEARNING OUTCOMES
CHAPTER IS TO:
• Discuss reasons why CDSSs are required both for prescribers and for AMS programs.
Delineate the factors • Describe the features of CDSSs that support antimicrobial prescribing.
and variables involved in
• Compare and contrast the different types of CDSSs.
prescribers’ decision-making
around antimicrobials. • To discuss the issues that may impact on the uptake of these systems into clinical
practice.
Outline the uses and
significance of computerised
decision support systems OVERVIEW
(CDSSs) in AMS programs.
Antimicrobial stewardship (AMS) refers to activities that optimise prescribing, enhance
treatment outcomes and potentially help mitigate the impact of the selection of pathogens
Describe different kinds of
with antimicrobial resistance. At the patient level in hospitals, prescribing involves and
CDSSs, and evaluate and
is underpinned by a complex range of decisions that are frequently based on poorly
present evidence of their
structured information. Clinicians need to consider a multitude of factors that will influence
impact on prescribing.
the quality of prescribing. Diagnostic criteria, disease severity, availability of microbiology
Understand the factors that results and susceptibility data, availability of antimicrobials, and patient factors all
influence successful determine and contribute to the prescriber’s decision-making, and impact on whether the
implementation of CDSSs. right drug is prescribed at the right time and for the right duration.
Decision-making is necessarily contingent and complex, and variable levels of adherence

to guidelines, where local or national guidelines are available, can be observed among
clinicians. There are multiple stakeholders as well as existing prescribing hierarchies
involved in decision making. (Figure 1) Senior clinicians with experience demonstrate
an increased ability to reduce the complexity of decisions around antibiotic prescribing,
and patients who go through infectious diseases consultations have better outcomes.
For clinicians with heavy workloads, less experienced or junior clinicians and clinicians
working in hospitals that do not have comprehensive infectious diseases support, access to
information technology (including computerised decision support) can be beneficial.

CHAPTER 24 - THE USE OF INFORMATION TECHNOLOGY TO SUPPORT ANTIMICROBIAL STEWARDSHIP
DEFINITION OF
COMPUTERISED
DECISION SUPPORT
“THE PROVISION OF CLINICAL
KNOWLEDGE, INTELLIGENTLY
FILTERED AND PRESENTED
AT APPROPRIATE TIMES, TO
ENHANCE PATIENT CARE”
Purcell GP. What makes a good clinical
decision support system. BMJ 2005;.
FIGURE 1
This figure describes the complex flow of information related to antimicrobial prescribing in a tertiary hospital intensive care unit. In this consolidated
flow chart, there are multiple stakeholders, multiple sources of information, and multiple users of this information. (Thursky KA, Mahemoff M. User-
centered design techniques for a computerised antibiotic decision support system in an intensive care unit. Int J Med Inform. 2007;76(10):760-8)

Decision support involves “the provision of clinical knowledge, sources. IT systems can thus support AMS programs in three
intelligently filtered and presented at appropriate times, to important ways – by providing decision support, recording and
enhance patient care”. Computerised decision support thus facilitating the informational workflow, and enabling auditing.
refers to the provision of electronically stored information that
Computerised decision support systems in antimicrobial
enhances and optimises clinicians’ decision-making at the point
stewardship are usually targeted at the prescriber or the AMS
of care.
team (or, in some cases, both). (Figure 2). The various types of
It is important to recognise that a computerised decision CDSSs are discussed below.
support system (CDSS) cannot replace infectious diseases
consultation and expert decision-making, but it can optimise 1. The prescriber
and enhance decisions at the point of care by bringing together Antimicrobial prescribing can be influenced by the use of
and synthesising patient-specific data, clinical guidelines and formulary restriction and antimicrobial approval processes, rules
information from other sources. CDSSs have the potential to and alerts. These are conceptualised as being part of restrictive
reduce the complexity of decision-making, improve the quality of approaches to AMS, whereas persuasive approaches include
decisions and increase the appropriateness of prescribing. the use of clinical guidelines and pathways. CDSSs may be
implemented as stand-alone systems or integrated with other
Importantly, in light of the challenges associated with drug-
hospital systems, including EMM/EMR systems. Use of the CDSS
resistant infections and risks posed by the inappropriate use of
may be forced (or mandatory) or voluntary (generally through
antimicrobials, CDSSs with post-prescription review and auditing
education, and hospital procedure and policy).
features can help health care providers keep track of prescribing
patterns within their units. Auditing and feedback from CDSSs 2. The AMS team
can guide internal quality control processes as well as contribute A key role of the AMS team is to undertake post-prescription
to local and national surveillance of antimicrobial use, thus review. This may be facilitated by systems that identify patients
informing AMS initiatives and interventions at various levels. Key for clinical review (e.g., approval systems and EMM or pharmacy
infectious diseases bodies support the use of CDSSs in AMS dispensing systems). There are many ‘back-end’ systems that link
programs, and have highlighted its potential to support quality patient data from multiple systems (pharmacy and microbiology).
improvement initiatives. Antimicrobial stewardship programs must undertake surveillance
of antimicrobial use and drug-resistant infections to monitor and
measure the impact of the programs. This requires the collection
and synthesisation of large amounts of data, including records
TOOLKIT RESOURCE of indications (if available), and prescribed agents, doses and
durations.
ARTICLES
Thursky K. Use of computerized decision support
systems to improve antibiotic prescribing. Expert
Rev Anti Infect Ther. 2006;4(3):491-507.
Sintchenko V, Coiera E, Gilbert GL. Decision support

systems for antibiotic prescribing. Curr Opin Infect
Dis. 2008;21(6):573-9
USING INFORMATION TECHNOLOGY TO

SUPPORT ANTIMICROBIAL STEWARDSHIP
A large amount of information (ideally presented in a timely
manner) about patients, likely pathogens, treatment options,
and potential drug interactions, contraindications and adverse
reactions needs to be considered by clinicians at the point of FIGURE 2
Usefulness of CDSSs in AMS programs
care. Decision-making can be optimised by the intelligent and
effective presentation of clinical guidelines, rules and alerts for
antimicrobials, or even computation of information from multiples

ARE ANTIMICROBIAL CDSSs EFFECTIVE? intranet or mobile applications) can easily be incorporated into
the clinical workflow and used at various entry points in hospital
Studies evaluating CDSSs have demonstrated that they can
systems. More complex CDSSs can be integrated with other
improve the quality and reduce the costs of antimicrobial
applications such as EMM systems, and can include advanced
prescribing.
decision support. Hospitals can have more than one tool to
• Outcomes associated with qualitative improvement such support their AMS program.
as increased appropriateness of prescribing, reduced
Currently, the most commonly used CDSSs for AMS are:
medication and dosing errors, and reduced incidence of
healthcare-associated infections have been observed. • electronic guidelines and mobile applications;
• From a cost perspective, CDSSs have been associated with • electronic antimicrobial approval systems;
significant cost avoidance or minimisation, with the literature • electronic infection prevention and surveillance systems; and
reporting savings in antimicrobial expenditure per patient or
for the hospital, and reductions in total medical expenditure • e-prescribing and EMM systems.
and length of stay.
Examples of Antibiotic Decision Support

•  Passive: Intranet/internet guidelines/apps
TOOLKIT RESOURCE • 
•  E.g., Smart phone apps
Pharmacy-based (back-end)
ARTICLES •  E.g., Aminoglycoside monitoring, redundant antibiotic combinations, therapeutic
mismatches
Baysari MT, Lehnbom EC, Li L, Hargreaves A, •  Approval systems

•  E.g., Guidance MS (Royal Melbourne Hospital)
Day RO, Westbrook JI. The effectiveness of
information technology to improve antimicrobial •  Computerised physician order entry/Electronic Medication
Management (EMM) system
prescribing in hospitals: A systematic review and
•  Advanced CDSS with/without order entry
meta-analysis. Int J Med Inform. 2016;92:15-34.
•  E.g., Antibiotic assistant/Theradoc (Hospira), TREAT (Tel-Aviv), Antimicrobial Resistance
Utilization and Surveillance Control (ARUS-C) (Singapore)
Cresswell K, Mozaffar H, Shah S, Sheikh A. A Thursky, K (2006). Use of computerized decision support systems to improve antibiotic prescribing. Expert Rev
Anti Infect Ther, 4:491-507. Sintchenko, V., et al. Decision support systems for antibiotic prescribing. Curr Opin
systematic assessment of review to promoting Infect Dis 21, (2008). Cresswell K et al. A systematic assessment of review to promoting the appropriate use of
antibiotics through hospital electronic prescribing systems. Int J Pharm Pract. 2016.
the appropriate use of antibiotics through
hospital electronic prescribing systems. Int J FIGURE 3
Pharm Pract. 2016. Examples of decision support
Yong, M. K., Buising, K. L., Cheng, A. C., & Thursky,

K. A. (2010). Improved susceptibility of Gram-
negative bacteria in an intensive care unit following
implementation of a computerized antibiotic
decision support system. Journal of Antimicrobial
Chemotherapy, 65 (5), 1062-1069.
TYPES OF ANTIMICROBIAL CDSSs

(See PDF Toolkit resources 1,3,4,5,6)
A range of CDSSs are available, and hospitals need to

carefully consider their requirements and local capacity for
implementation. (Figure 3 and Figure 4) FIGURE 4
There are multiple options for introducing decision support for AMS
A CDSS can be as simple as an online portal containing
programs
guidelines and formulary restrictions. Passive decision support
through electronic access to guidelines (on the Internet, hospital

Mobile applications Antibiotic Pocket Borm Bruckmeier Publishing,

Clinical portals, including those containing guidelines, are LLC Medica
increasingly becoming mobile device-compatible, ensuring https://itunes.apple.com/
that with increased smartphone use among clinicians, passive us/app/antibiotics-pocket/
decision support becomes more accessible at the point of care. id434810841?mt=8
• In addition to traditional resources such as pocket guides, Spectrum MD - Localized https://play.google.com/
reference handbooks and computer desktop-accessible Antimicrobial Stewardship store/apps/details?id=com.
portals, mobile apps and mobile browser-compatible spectrum&hl=en_GB
portals can serve as suitable platforms for the dissemination Impact Infection Control Branch,
of clinical practice guidelines, and are likely to be consulted Centre for Health Protection,
more frequently due to their accessibility and availability at Department of Health, Hong
the bedside. Kong
• AMS opportunities include disease- or drug-based guidelines, http://www.chp.gov.hk/en/

calculators and dissemination of data such as antibiograms. static/40563.html
CBR-based Imperial Antibiotic Imperial College London
• Importantly, these platforms allow guidelines and other
Prescribing Policy (ENIAPP) http://www.imperial.
supplementary information to be updated more easily.
smartphone app ac.uk/medicine/hpru-amr/
The following table provides some examples of mobile applications-and-tools/
applications that have been used for AMS: imperial-antibiotic-prescribing-
policy-iapp/
Imperial College Antibiotic Imperial college, London
Prescribing Policy App (IAPP) A few points about the effectiveness of apps need to be
http://www.imperial.
considered.
ac.uk/medicine/hpru-amr/
applications-and-tools/ • While third-party apps are also available, these may
imperial-antibiotic-prescribing- not support or be compliant with local practices or clinical
policy-iapp/ guidelines, although the option of local customisation is
Sanford Guide Online Sanford Guide offered by some apps.
https://www.sanfordguide. • A potential cause for concern is the fact that users must
com/ generate updates on their own devices, which could lead to
John Hopkins Antibiotic Guide Johns Hopkins Medicine problems with version control.
http://www.hopkinsmedicine. • Further, as they provide passive decision support, there is

org/apps/all-apps/johns- some uncertainty about the impact of mobile apps.
hopkins-abx-guide-2017
• It is unclear whether these tools lead to sustained change in
Microguide Horizon Strategic Partners, UK prescribing behaviour. One reason may be that key decisions
https://itunes.apple.com/ are often made on the ward round by a senior consultant or
gb/app/microguide/ fellow. Passive apps provide less incentive than systems that
id447171786?mt=8 are able to provide patient-specific information.
015 EMRA Antibiotic Guide Emergency Medicines
Residents Association, US

https://itunes.apple.com/us/
app/2017-emra-antibiotic- TOOLKIT RESOURCE
guide/id1164251928?mt=8 ARTICLES
UptoDate Online https://www.uptodate.com/
Goff DA. iPhones, iPads, and medical applications
home/product
for antimicrobial stewardship. Pharmacotherapy.
2012;32(7):657-61

Electronic antimicrobial approval systems
Antimicrobial authorisation and approval systems that support

CASE STUDY: ANTIMICROBIAL
formulary control and indication restrictions can underpin and
RESTRICTION AND APPROVALS
form part of restrictive and persuasive AMS strategies. Guidance MS™ (Royal Melbourne Hospital, Australia) is
used in 70 Australian hospitals, including public, private,
• Approval systems, either integrated with hospital EPS/EMM
metropolitan and regional hospitals. The program supports
systems, or implemented autonomously in the absence of
a number of AMS interventions, including formulary control;
these systems, are being adopted by several institutions
restriction of indications for target antimicrobials; access
around the world.
to national guidelines; alerts for non-standard indications;
• The core function of an electronic approval system is to administration alerts by pharmacists when medications
support the local antimicrobial formulary (through are given without approval; and targeted post-prescription
customisation of algorithms for ‘restricted’ antimicrobials review, feedback and reporting. This system has been
and approved indications) and provide an approval process associated with:
for prescribers and pharmacists. It can do this by generating
• reduced consumption of targeted or ‘restricted’
alerts that require the AMS team to act (by undertaking post-
antimicrobials (e.g., third-generation cephalosporins)
prescription review, for example).
and increased consumption of narrow spectrum
• To ensure approval systems fit comfortably into the workflow, antimicrobials (e.g., benzylpenicillin, doxycycline and
the AMS team can determine locally-relevant criteria for the aminopenicillins);
generation of alerts and thus customise the approval process. • improved resistance patterns in some Gram-negative
Implementation experience indicates that approval systems isolates in intensive care units. (REF 2)
cannot be proposed as a replacement for expert decision- A network of 5 hospitals using Guidance as a centrally-
making but can improve the quality of prescribing by helping deployed CDSS (and operating coordinated AMS programs
direct the attention of expert prescribers and the AMS team to on the basis of a ‘hub and spoke’ model) witnessed
prescriptions that require review. improved antimicrobial use, reduced costs and better
treatment outcomes. (REF 1) Data from the Australian
Importantly, an electronic approval system enables auditing
National Antimicrobial Prescribing Survey, a program
of antimicrobial use, and facilitates feedback to individual
contributing to national surveillance of antimicrobial use
prescribers and AMS teams within units (the persuasive
in Australia, showed that hospitals using Guidance had a
component of AMS). This necessitates collaboration among staff
higher mean appropriateness of antimicrobial prescribing
and units.
(in 2014, 82.2%, n=1518 prescriptions) compared to the
• For the successful implementation of an approval system, national average in Peer Group A hospitals (74.4%,
it will be essential to expedite, secure and maintain ongoing n=10,955 prescriptions).
collaboration between pharmacy, microbiology and infectious
diseases staff, and staff in individual hospital units.
• As part of this process, local customisation of the formulary

and indications for use, as determined by the AMS team or
therapeutics team, may also be required.
As approval systems have been implemented at several

institutions, there is now considerable research focused on
evaluation of their impacts. Approval systems have been TOOLKIT RESOURCE
found to be very effective in reducing consumption of targeted ARTICLES
antimicrobials as well as medicine costs.
Buising KL, Thursky KA, Robertson MB, Black
Any system that requests an indication (e.g., an approval system JF, Street AC, Richards MJ, et al. Electronic
or EPS) is open to ‘gaming’ by prescribers, as indications can antibiotic stewardship--reduced consumption
be erroneously or deliberately selected to provide access to of broad-spectrum antibiotics using a computerized
particular antimicrobials. antimicrobial approval system in a hospital setting.
J Antimicrob Chemother. 2008

Sentri7 Wolters Kluwer
TOOLKIT RESOURCE http://www.pharmacyonesource.com/

products/sentri7/
ARTICLES ICNET ICNET systems, Illinois
Bond, S. E., Chubaty, A. J., Adhikari, S., Miyakis, http://www.icnetplc.com/
S., Boutlis, C. S., Yeo, W. W., Batterham, M.J., RL Solutions RL, Ontario, Canada
Dickson, C., McMullan, B.J., Mostaghim, M. & Li- http://www.rlsolutions.com/rl-products/
Yan Hui, S. (2017). Outcomes of multisite infection-surveillance
antimicrobial stewardship programme
QC Pathfinder Vecna Technologies, Cambridge,
implementation with a shared clinical decision
Massachusetts
support system. Journal of Antimicrobial
https://www.vecna.com/vecna-medical-
Chemotherapy, 72(7), 2110-2118
launches-qc-pathfinder-version-6-0-with-
updated-nhsn-reporting-capabilities-and-
pharmacy-intervention-tracking/
Infection prevention and surveillance systems
Infection prevention systems can provide decision support to A number of factors relating to the implementation of infection
AMS teams based on the integration of data from pharmacy prevention systems need to be considered.
dispensing and laboratory systems, diagnostic imaging systems • Infrastructure and implementation issues, such as the lack of
and the EHR. These systems work at the ‘back-end’ and interoperability between legacy pathology and pharmacy
require dedicated staff to review the reports and alerts that are systems, and lack of adequate support for integration, may
generated and then to act on them. The type of interventions prevent facilities from adopting third-party infection
that can be undertaken include: prevention systems.
• Rules-based alerts for bug-drug mismatches (e.g., a • Like approval systems, infection prevention systems require a
prescription for an antimicrobial in a setting of known clinical workforce to monitor and act on alerts, and generate
resistance), redundant anaerobic coverage, positive blood reports and feedback.
cultures, etc.
• The level of sophistication of the reports provided by these
The benefits of infection prevention systems include: systems depends on the level of integration with pathology
and pharmacology. Many will provide real-time run charts of
• They can help identify patients at risk of developing
target pathogens (e.g., Staphylococcus aureus bacteremia) or
nosocomial infections, monitor antimicrobial resistance, and
clinical conditions (e.g., hospital acquired pneumonia).
assist with routine surveillance activities, including reporting
and generating antibiograms. • Infection prevention programs should be differentiated from
hospital microbiology systems. Hospital microbiology
• They can help improve antimicrobial dosing and monitoring.
programs can also support AMS by providing
The following table provides examples of commercial electronic
recommendations about the clinical significance of a result
infection prevention systems:
(e.g., Candida in sputum is rarely a pathogen), as well as
limiting the presentation of antibiotics that the pathogen is
Safety Surveillor Premier HealthCare, Charlotte, North susceptible to to avoid broad spectrum use (known as
Carolina cascade reporting).
https://www.premierinc.com/transforming-
Electronic prescribing, medication management systems:
healthcare/healthcare-performance-
developing antibiograms; tracking DOTs or DDDs/ 1000
improvement/patient-safety/
patient days; developing ad hoc reports to monitor AMS
Theradoc Premier HealthCare, Charlotte, North
team interventions
Carolina
http://www.theradoc.com/ EPS/EMM systems are information systems that allow clinicians
to generate electronic medication prescriptions. EMM systems
MedMined CareFusion, BD, New Jersey
encompass the following functions:
https://www.bd.com/en-us/offerings/brands/
medmined

• computerised entry of physician orders (e-prescribing); • untimely transmission of discontinuation orders from the
prescriber to the pharmacy;
• medication review;
• high order override rates (>90%) arising from inconsistent
• dispensing;
decision support mechanisms; and
• recording of medicines administration; and
• pre-set, off-the-shelf drug databases that are not amenable
• decision support (optional). to local customisation.
Most commercial EPSs have features associated with front-end Many of these systems are focused on ‘front-end’ decision
decision support that can be support AMS. support. They are effective in reducing transcription errors and
• These include attributes such as default values, routes of improving the quality of the prescription. However, they are less
administration, doses and frequencies. effective in identifying the wrong choice of drug, which points to
the need for post-prescription review.
• These may also include allergy alerts and drug interaction
alerts. Some systems provide dedicated AMS modules that identify
patients that would benefit from AMS review. These might
• EMM systems can support a bundle of interventions, include patients with blood stream infections, or other
including antimicrobial restriction, dosing recommendations, pathogens (e.g., C.difficile), patients prescribed particular
rules-based alerts and order sets for disease conditions. target antimicrobials (criteria may include cost, toxicity or
• An important advantage of these systems is that they can spectrum, or non-guideline approved drugs), patients suitable
capture all the details of the antimicrobials prescribed and for IV-to-oral switch or dose optimisation, including therapeutic
administered to the patient. This enables reporting of days dose monitoring.
of therapy (DOT) per 1000 patient days rather than the These systems may have the ability to provide ad-hoc reports
standard approach of defined daily doses (DDDs). Defined or formatted reports to monitor the AMS team’s interventions
daily doses are less meaningful and cannot be used for
paediatric patients.
Studies have shown that EMM systems can have an impact on

prescribing and patient outcomes: TOOLKIT RESOURCE
• Cost-effectiveness studies have demonstrated that EMM ARTICLES
systems, particularly those with decision-support functionality,
Forrest GN, Van Schooneveld TC, Kullar R,
can lead to long-term savings due to reductions in adverse
Schulz LT, Duong P and Postelnick M. Use of
drug events, readmissions and healthcare costs.
electronic health records and clinical decision
• There are a few well-designed studies that have support systems for antimicrobial stewardship.
demonstrated reduction in mortality, length of stay and Clin Infect Dis. 2014; 59 Suppl 3: S122-33
readmission for patients admitted with community-acquired
pneumonia and sepsis. Schiff GD, Amato MG, Eguale T, Boehne JJ, Wright
However, a few implementation-related concerns need to A, Koppel R, et al. Computerised physician order
be considered. Poor implementation of systems and lack of entry-related medication errors: analysis of reported
decision-support (e.g., error checking) can lead to patient harm. errors and vulnerability testing of current systems.
It is critically important that the AMS team is involved during the BMJ Qual Saf. 2015;24(4):264-71
implementation of these systems to ensure that rules-based
alerts and knowledge bases are locally applicable. Significant
resources are required for local customisation of pre-set content.
Studies evaluating EMM systems have highlighted features,
outcomes and procedural issues that could negatively impact DISCUSSION OF ISSUES AROUND
antimicrobial prescribing: ALERT FATIGUE IN EMRS
• large numbers of drug and dosing combinations;
• erroneous auto-complete directions that contradict WATCH VIDEO

intended orders;

studies relating to AMS, surgical prophylaxis and adverse

drug events.
A recent poster presented at ID Week in
2017 described the impact of the Epic® Nascent machine learning and text-mining mechanisms, such as
Antimicrobial Stewardship Module in an 805- those deployed by one tool that can predict invasive pulmonary
fungal infection from computed tomography (CT) reports,
bed US metropolitan hospital. The program
have the potential to be incorporated into AMS systems. For
significantly improved the efficiency of the example, a Canadian CDSS was augmented with machine-
ASP, increasing the number of antimicrobials learning capabilities to identify inappropriate prescriptions and
reviewed by 5442 to 8288 in a 12-month recommend changes (including dose and dosing frequency
period before and after the implementation adjustments, discontinuation of therapy, early switch from
(from ~14 to 22 prescriptions per day). The intravenous to oral therapy, and changes relating to redundant
antimicrobial spectrum).
proportion of interventions increased from
36% to 89% of prescriptions, mainly in Advanced CDSSs also have a potential role in the detection
optimisation of therapy (dose and alternative and management of sepsis in hospitals with EHRs. A system
that generated early sepsis alerts using data from disparate
therapy) and safety/monitoring (TDM, bug-
clinical portals was associated with improved care and patient
drug mismatch review, recommendation for
outcomes. However, a recent systematic review of eight studies
follow-up cultures, request for additional has found sepsis alerts systems to have limited predictive value
sensitivities, and ophthalmology consult for for individual patients.
candidemia). The program did not lead to
improvements in de-escalation and cost-
savings.
N.Pettit et al. Open Forum Infectious Diseases,
TOOLKIT RESOURCE
Volume 4, Issue suppl_1, 1 October 2017, ARTICLES
Pages S263–S264, https://doi.org/10.1093/ Paul, M., Andreassen, S., Tacconelli, E., Nielsen,
ofid/ofx163.580 A. D., Almanasreh, N., Frank, U., Cauda, R. &
Leibovici, L. (2006). Improving empirical antibiotic
treatment using TREAT, a computerized decision
support system: cluster randomized trial. Journal
of Antimicrobial Chemotherapy, 58 (6), 1238-1245
Advanced decision support systems
Advanced decision support systems use complex logic, Evans RS, Pestotnik SL, Classen DC, Clemmer
mathematical modelling or case-based probabilities to provide TP, Weaver LK, Orme JF, et al. A computer-
patient-specific recommendations. They can provide decision assisted management program for antibiotics and
support by helping identify potential infections, pathogens and other antiinfective agents. N Engl J Med.
treatment options based on inputs about patient symptoms, 1998;338:232-8
for example. A few systems have been successfully trialled and
implemented.
• TREAT (Treat Systems, Denmark) is a CDSS that uses

mathematical models to predict sites of infection and specific
pathogens. A cluster-randomised trial across three wards in
three countries demonstrated that the system was associated
with improved appropriateness of empirical antimicrobial
therapy and patient outcomes.
• The Antimicrobial Assistant system, developed by the Latter-

Day Saints Hospital in Utah, was an early leader in advanced
decision support. It used predictive models for infection
control and surveillance, and its impacts were evaluated in

WHAT ARE THE FACTORS THAT ARE LIKELY Technical readiness

TO RESULT IN SUCCESSFUL • IT infrastructure
• IT resources
IMPLEMENTATION OF A CDSS?
There are factors intrinsic to the proposed software that will Resource
readiness
influence uptake by clinicians, and these should be considered Administrative readiness
• Financial
when deciding on the choice of CDSS. • Executive support • Human
• Antimicrobial stewardship
committee
Implementation of new technology into the clinical workflow
requires very careful planning that needs to be started many
months in advance. (See Figure 5)
Staff skills
Cultural factors, such as institutional dynamics, capacity Structural readiness
characteristics • Education
for collaboration between hospital units, and support • Culture • Project officer
for interventions and initiatives, can play a critical role in • Infectious
diseases service
determining the success of AMS programs (even without
information technology). For CDSS-supported AMS programs to Process readiness
• Implementation plan
be successful, technical readiness (e.g., strong IT infrastructure • Existing antimicrobial
stewardship program
and server, and dedicated IT resources), administrative
readiness (e.g., executive support), and an appropriately trained
FIGURE 5
project officer (often a clinical pharmacist) to oversee the
Factors influencing organisational readiness and resources required
implementation and training are necessary. (See Figure 6) for implementation of a CDSS as part of an AMS program
It is really important for AMS team members to be formally
engaged in all CDSS implementation activities, from scoping
and developing functional specifications through to the final
deployment. The development or local customisation of
content for these systems is time-consuming. Introduction of
antimicrobial restrictions (for example) needs to be discussed
with each hospital unit, and appropriate training organised for
clinical staff. Measuring user acceptance after implementation
and continually monitoring uptake and usage is essential.
While the consolidation of data using CDSSs provides enormous

opportunity for AMS programs, it is important to consider both
the quality and volume of the alerts. One hospital’s experience
with one of these systems found that of a total of 8,571 alerts
that were generated for 791 patients over a five-month period,
only 284 interventions were made. 2–3 hours per day were
required for review, and 1–2 hours per day for intervention
and documentation. Data overload and alert fatigue is a very
FIGURE 6
important issue for AMS programs, highlighting the importance Features of CDDSs and factors that are likely to increase clinician
of triaging workflow. uptake.

TOOLKIT RESOURCE
ARTICLE
Bates DW, Kuperman GJ, Wang S, Gandhi T, Kittler
A, Volk L, et al. Ten commandments for effective
clinical decision support: making the practice of
evidence-based medicine a reality. J Am Med
Inform Assoc. 2003;10(6):523-30

SUMMARY
• CDSSs are useful tools in AMS programs. A range of CDSS • AMS teams should consider existing and planned IT
options, based on different approaches to decision support, infrastructure when adopting a CDSS, and aim for the
are available, including mobile applications, approval integration of systems where possible.
systems, surveillance programs and EMR/EMM systems. • Integration of CDSSs with existing hospital systems
• CDSSs are simply assistive tools and cannot replace expert usually requires customisation and modification to ensure
decision-making. They may support the prescriber or the AMS interoperability.
program, or both.
• Organisational and workflow factors can determine the

effectiveness of a CDSS. There should be an established AMS
program in place prior to implementation.
CDSS TYPE INTERVENTION ADVANTAGES AND

OPPORTUNITIES DISADVANTAGES
Smartphone applications Passive Dissemination of guidelines Rapid dissemination
• Disease-based Useful for hospitals with poor IT
• Drug-based infrastructure
Calculators (dosing) Not usually integrated with

hospital systems
Antibiograms
Uncontrolled use, including
version control
May not influence prescribing
of senior clinicians
Infection Prevention Back-end Pharmacy +/- laboratory Support an organisational
Surveillance Systems (Asynchronous) integration approach
Rule based alerts: Can be integrated with an EMR
• Drug-bug mismatches Requires substantial resources
• Double coverage to review reports and to
determine clinically relevant
Monitor restricted drug usage
alerts that need action
Surveillance - real-time alerts
Requires dedicated EFT to
support
Commercial systems can be
expensive
Approval systems (standalone) Front-end Enforce formulary Can work well in the absence
May be pre-prescription of EHR or EPS
or post-prescription (after Support an organisational
dispensing) approach to AMS
Enforce approved indications Best combined with an
by drug antimicrobial team to review
Educational opportunity for the patients at a time period post
prescriber approval 24-48 hours
Can include clinical decision

support
Reports and feedback

CPOE/EMR Front-end Error alerts - allergy, dosing, Will reduce transcription

EMR Front end medicine-medicine interactions errors but incorrect choice or
indication may not be impacted
Chart abstraction tools
to screen and identify Best combined with CDSS
patients at risk for sepsis, or
Real time interventions and
collate information for AMS
alerts possible but alert fatigue
(medicines, results)
is very common
Pre-prescription restriction
Allows for retrieval of data for
rules
research
Record AMS recommendations
Patient-centred rather than
and interventions
organisational
Support order sets for
Requires additional resources
syndromes (e.g., community-
to develop customised AMS
acquired pneumonia, sepsis)
reports
Alerts and triggers to
Significant time required by
identify patients suitable for
hospital IT and investment by
intravenous-to-oral switch
the institution to create the
AMS review care protocols tools
(templates or phased order
Eliminates the cost of external
sets)
vendor
Templates must be
incorporated into EMR at each
site
Less responsive to change

Advanced CDSS Causal probabilistic network Complex, usually ‘home-grown’
approach to identification of systems
pathogens, by specimen type Currently in early phase of
or underlying conditions of adoption.
patient
Case-based probability
Machine learning algorithms
Pathogen prediction

CHAPTER 25
AUTHOR: ENRIQUE CASTRO SANCHEZ
THE ROLE OF THE NURSE

IN STEWARDSHIP

THE AIM OF THIS
LEARNING OUTCOMES
CHAPTER IS TO: On completion of this chapter, the participant should be able to:
1 Why should nurses be involved in antimicrobial stewardship?
This chapter justifies the
participation of nurses in a. Describe drivers for participation of nurses in antimicrobial stewardship activities.
antimicrobial stewardship and 2 Expanding the participation of nurses in antimicrobial stewardship
the benefits of including them a. Identify how antimicrobial documents and policies consider nursing participation
as core components of in stewardship.
stewardship teams. Different
b. Explain antimicrobial stewardship clinical tasks that could be adopted by nurses.
drivers encouraging the
participation of nurses, such as c. Consider the impact in antimicrobial usage of advanced nursing roles such as
operational and organisational prescribing.
factors are discussed. 3 Public health and community nursing contribution to stewardship
Following that, some of the a. Critically argue some public health nursing behaviours that could be embedded
clinical tasks and roles that can within antimicrobial stewardship frameworks.
be readily assumed by nurses b. Reflect on emerging activities in nursing homes and long-term care facilities that
in hospitals and community would benefit antimicrobial stewardship initiatives.
settings are discussed, including 4 Integration between nursing roles and activities in AMR and other professionals
prescribing. The chapter presents
a. Understand the areas for antimicrobial stewardship synergy and integration
some ideas about the importance
between nurses and other professionals.
of integrating non-clinical nursing
5 Stewardship, a target for nurses in executive and directive positions.
staff, such as executives and
managers, into stewardship b. Discuss how nurses in executive and directive positions can contribute to and
efforts and with other strengthen antimicrobial stewardship programmes.
healthcare professionals. 6 Nurse-focused interventions in antimicrobial stewardship
Finally, the chapter briefly a. Reflect upon some existing nurse-centred stewardship interventions.
reviews some of the experiences 7 Barriers to resolve the participation of nurses in stewardship
already published reporting a. Examine some of the barriers to increased involvement of nurses in stewardship.
on nurse-led or nurse-focused
b. Evaluate existing initiatives implemented to address barriers to nurse
interventions, concluding with
involvement.
some of the remaining barriers
to be addressed before
participation of nurses in
stewardship programmes can
be extended and scaled-up.

CHAPTER 25 - THE ROLE OF THE NURSE IN STEWARDSHIP
WHY SHOULD NURSES BE INVOLVED Developing nursing-based interventions and fostering the
IN STEWARDSHIP? interest and participation of nurses in stewardship makes sense
for many reasons. Nurses are the largest and most consistent
Due to the size of the challenge posed by drug-resistance
healthcare workforce, with 19.3 million nurses worldwide
infections worldwide, there have been calls to increase the
(World Health Organization's World Health Statistics Report,
number of health care workers involved in optimal antimicrobial
2011). All healthcare systems around the world have nurses: for
stewardship (AMS) interventions
example, there were ~100,000 doctors in the UK in 2017, but just
under 300,000 registered nurses (http://www.nhsconfed.org/
“Governments, healthcare system resources/key-statistics-on-the-nhs); in the US, just over 4 million
leaders, and private actors should nurses were professionally active in 2017 (http://www.kff.org/
expand funding opportunities to other/state-indicator/total-registered-nurses/); and in India, there

are approximately 1.5 million nursing professionals (WHO, World
increase the essential health workers Health Statistics Report 2011).
on the frontline of fighting resistance”
Tackling drug-resistant infections globally: final report and
recommendations the review on antimicrobial resistance chaired by WHY SHOULD NURSES BE
jim o’neill may 2016. https://amr-review.Org/sites/default/files/160525_
final%20paper_with%20cover.Pdf INVOLVED IN STEWARDSHIP
PROGRAMS?
However, by 2035 healthcare systems around the world will
face a shortage of just under 13 million professionals (WHO, A WATCH VIDEO
universal truth: No health without a workforce, 2014). Successful
AMS programmes will therefore have to strengthen existing
cadres of professionals involved, whilst increasing the general
stewardship workforce. Additionally, in many settings around the world the relative
availability of nurses may help address the chronic undersupply
of medically trained healthcare professionals. Thus, tasks and
roles traditionally carried out by physicians and surgeons may
need to be performed by nurses, with adequate support, training
and supervision.
FIGURE 1 Ratio (per 1000 population)
Ratio of nurses <2.000
& midwives to 2.000-3.999

4.000-5.999
physicians,
6.000-9.999
worldwide
10.000-14.999
>15.000
Date not available
Not applicable

Increasing stewardship capacity by adding a proportion of the

nursing workforce (say, 1%) to AMS interventions could therefore
be a powerful antimicrobial quality improvement measure. PROPOSED CORE
COMPOSITION OF
ANTIMICROBIAL
STEWARDSHIP TEAMS
Ratio (per 1000 population)

<2.000
2.000-3.999
+1% - INFECTIOUS DISEASES PHYSICIAN
- CLINICAL MICROBIOLOGIST
- CLINICAL PHARMACIST WITH
4.000-5.999
6.000-9.999
EXPERTISE IN INFECTION
10.000-14.999
>15.000
Date not available
- OTHER MEMBERS COULD BE
Not applicable
SPECIALIST NURSES, FOR EXAMPLE
INFECTION PREVENTION OR
STEWARDSHIP NURSES…
EXPANDING THE PARTICIPATION OF (Nathwani, 2012)
NURSES IN ANTIMICROBIAL STEWARDSHIP

Many authors have already proposed that antimicrobial efforts
In fact, some authors argue that the participation of nurses in
should consciously include nursing participation (Charani et
stewardship may be extensive but ‘unrecognised’ (Olans et al,
al, 2013; Edwards et al, 2011), a gradual shift from earlier views
2016). Some roles that appear naturally linked to stewardship
about the optimal composition of antimicrobial stewardship
activities are presented in Figure 2.
teams (IDSA, 1997). These initial ideas did not offer much
scope to nurses, unlike more recent perspectives that endorse
‘interprofessional efforts across the continuum of care’ and
recognize a typical team core comprised of:

TOOLKIT RESOURCE
SITE LINK
Charani E, Holmes AH. Antimicrobial stewardship
programmes: the need for wider engagement. BMJ
Qual Saf. 2013;22:885-887
ARTICLE
Edwards R, Drumright L, Kiernan M, Holmes A.
Covering more Territory to Fight Resistance:
Considering Nurses’ Role in Antimicrobial
FIGURE 2
Stewardship. J Infect Prev. 2011;12(1):6-10.
Nursing input in AMS across the clinical pathway (Olans, 2015)
doi:10.1177/1757177410389627

• Antimicrobial administration is adapted to clinical needs as

well as patient condition (i.e., evaluating oral routes if
ROLE OF NURSES IN clinically appropriate).
ANTIMICROBIAL STEWARDSHIP • Improvements in the patient condition inform clinical
PROGRAMS decisions (e.g. to stop antibiotics).
• Patients and healthcare professionals are informed and

WATCH VIDEO educated about optimal antimicrobial use.
• Audits of antimicrobial use are supported by nurses.
WHAT CAN NURSES DO TO

COMBAT ANTIMICROBIAL
RESISTANCE?
WATCH VIDEO

TOOLKIT RESOURCE
SITE LINK FIGURE 3
Olans RN, Olans RD, DeMaria A. The Critical Some clinical nursing roles in antimicrobial stewardship
Key: MC&S = Microscopy, culture and sensitivity; TDM = therapeutic
Role of the Staff Nurse in Antimicrobial
drug monitoring (e.g. gentamicin, vancomycin)
Stewardship—Unrecognized, but Already There.
Clin Infect Dis. 2016; 62(1): 84–89
PDF ARTICLE ACCESS PODCAST

Nathwani D. (2012) Practical Guide to Antimicrobial
Stewardship in Hospitals
Depending on the setting and local scope of practice, nurses

may be able to perform advanced roles, managing patients
autonomously by, for example, prescribing antibiotics. For these
Nurses could ensure that: cadres, it has been suggested that capacity-building, consulting
• Adequate microbiological samples for culture and sensitivity and supporting others to use antimicrobials optimally may be as
are obtained prior to instigation of any antimicrobial therapy, crucial as clinical aspects (Manning, 2014).
if allowed by the patient’s clinical condition (i.e., if the patient Videos from Castro-Sanchez:
has sepsis and is not catheterised, it is inappropriate to wait
for a urine specimen, although it is nearly always possible to
perform a blood culture prior to antibiotic commencement).
• Laboratory results are communicated in a timely manner

WATCH VIDEO
and consideration given to the impact of results on existing
therapeutic decisions.
• Prescribed antimicrobials reflect local and national guidelines,

as relevant.
WATCH VIDEO
• Antimicrobial doses are not missed and are administered
according to optimal dose intervals.

Should this trend in prescribing continue, in the near future

community-based nurse prescribers may be responsible for more
SUGGESTED antimicrobial prescriptions than the volume issued in hospitals.
ANTIMICROBIAL Additionally, in the last five years, prescribing of antimicrobials
STEWARDSHIP by nurses appears to represent a growing proportion of all nurse
ACTIONS FOR NURSES prescriptions (Figure 5).
IN ADVANCED PRACTICE
ROLES
- ADVANCE OWN KNOWLEDGE ABOUT
ANTIBIOTICS
- OPTIMIZE ANTIBIOTIC PRESCRIBING
PERFORMANCE AND PRACTICE
- ADVOCATE ADOPTION OF
RECOMMENDED ACTIONS IN
PRACTICE SETTING
- REACH OUT AND CONNECT WITH
LOCAL NURSES IN ADVANCED
PRACTICE ROLES
(Manning, 2014)
FIGURE 5
The impact on antimicrobial use of the growing number of nurse From: Ness V, Malcolm W, McGivern G, Reilly J. Growth in nurse
prescribers worldwide will require increased attention. Recent prescribing of antibiotics: the Scottish experience 2007–13. J
data suggests that in Scotland nurses were responsible for more Antimicrob Chemother 2015; 70: 3384–3389
than 5% of antimicrobials prescribed in the community (Figure 4). https://academic.oup.com/jac/article-lookup/doi/10.1093/jac/dkv255
PUBLIC HEALTH AND COMMUNITY

NURSING CONTRIBUTION TO
The largest proportion of antimicrobials is prescribed in
community settings, where nurses can potentially influence
decisions. Further, there is an increased recognition of wider
public health determinants of antimicrobial exposure that offer
opportunities for nurses to act. For example, and in recognition
of those determinants, the Royal College of Nursing in the UK
launched in 2014 a statement about antimicrobial resistance that
highlighted the crucial role of nurses to:
• Reducing demand for antibiotics.
FIGURE 4 • Influencing public and patient knowledge and expectations of

Scottish Antimicrobial use and resistance in humans (2015) antibiotic prescribing through their societal contacts.
https://www.isdscotland.org/Health-Topics/Prescribing-and-
• Leading and implementing immunisation programmes across
Medicines/Publications/2016-08-30/2016-08-30-SAPG-2015-Report.
pdf?25829714537 all age groups to prevent avoidable infection and associated
morbidity and mortality.

• Leading and implementing public health strategies to support Whilst obviously some responsibilities such as establishing
the public to ‘live well’ and prevent or reduce the burden of a diagnosis and carrying out a comprehensive medical
long term conditions such as diabetes, liver disease, obesity. assessment are to be carried out by doctors, other
responsibilities could be shared, or integrated, among the
Equally, nurses could be instrumental in leading, supporting,
components of the healthcare team. For example, establishing
implementing and evaluating antimicrobial improvement
the allergy status of a patient; timely initiation of antimicrobials;
initiatives in nursing homes or long-term care facilities
monitoring therapeutic drug levels; adhering to optimal infection
prevention and control practice, etc., could be collaborative
roles (Castro-Sanchez et al, 2017).
VISIT SITE

TOOLKIT RESOURCE
SITE LINK
CDC. 2017. The Core Elements of Antibiotic
Stewardship for Nursing Homes
In these settings, skilled nurses should balance the increased

vulnerability and frailty of patients with the careful use of
FIGURE 6
screening and diagnostic tests as well as the meticulous
Integration of nursing, medicine and pharmacy stewardship
management of invasive devices. For example, avoiding interventions (Castro-Sánchez et al, 2017)
measures that have limited or no clinical benefit yet can trigger
antimicrobial prescriptions, such as routine urine sampling, could
be led, implemented and evaluated by nurses (Health Protection STEWARDSHIP, A TARGET FOR NURSES
Agency, 2017) IN EXECUTIVE AND DIRECTIVE POSITIONS
• AMS and Nursing Homes - how can nurses make a In addition to fostering new clinical roles related to AMS,
difference? organisations would benefit from raising the awareness of
antimicrobial resistance at nursing executive and board levels.
It is likely that engaged board members and managers could
have an impact on stewardship initiatives similar to that
VIEW DOCUMENT achieved in hand hygiene and infection prevention and control
programmes. Further, demonstrating and developing a link
to those programmes as well as patient safety and quality
improvement interventions may be useful starting points to
engage with hospital executives.
INTEGRATION BETWEEN NURSING
ROLES AND ACTIVITIES IN AMR AND Recommendations from the American Nurses Association/
OTHER PROFESSIONALS Centers for Disease Control and Prevention Workgroup on
the Role of Registered Nurses in Hospital Antibiotic
Whilst encouraging the participation of nurses in AMS
Stewardship Practices
activities can be beneficial on many levels, including
new professional cadres and increasing the AMS-related
interventions of existing professionals can have unintended
consequences or lead to inefficiencies, if the process is not
mapped, supported and audited.
VIEW DOCUMENT

NURSE-FOCUSED INTERVENTIONS IN Similar improvements were seen in care homes where an online
ANTIMICROBIAL STEWARDSHIP educational intervention was implemented (Wilson et al, 2017).
The course improved knowledge, beliefs and attitudes of nurses
An Australian study (Gillespie, 2013) emphasised the opportunity
towards AMS and was associated with an increased participation
for nurses and nurse education to influence the intravenous-
in stewardship activities.
to-oral switch decision, as a collaborative exercise between
pharmacists, nurses, and doctors (Figure 9). Following education
there was an increase in instances where nurses said they would
question the need for intravenous antibiotics from 14% to 42%
CONFIDENCE RELATED TO
(P<.001).
LEARNING OBJECTIVE FOR
28%
EACH MODULE
ATTITUDES TOWARD CLINICAL

ASSESSMENT OF RESIDENTS
IN DISCUSSIONS
ABOUT IV TO PO SWITCH ATTITUDES REGARDING ROLE IN
ATTITUDES ABOUT
TOOLKIT RESOURCE ANTIMICROBIAL STEWARDSHIP
SITE LINK
BELIEFS ABOUT ANTIMICROBIAL
Gillespie E, Rodrigues A, Wright L, Williams N, Stuart STEWARDSHIP AND INFECTION
RL. Improving antibiotic stewardship by involving CONTROL AND PREVENTION
nurses. Am J Infect Control. 2013 Apr;41(4):365-7.
doi: 10.1016/j.ajic.2012.04.336. (Wilson, 2017)

TOOLKIT RESOURCE
SITE LINK
Wilson BM, Shick S, Carter RR, et al. An online
course improves nurses' awareness of their role
as antimicrobial stewards in nursing homes.
Am J Infect Control, 2017
Interesting experiences led and managed by nurses have

also been reported in low- and middle-income countries; an
increasing response and activity by nurses in these settings is
likely to be vital in the global response to AMR.
Broad Spectrum Coverage: Cross-Professional Engagement to

fight antimicrobial resistance in South Africa:
FIGURE 7
Effect of an educational intervention on nursing knowledge about
antimicrobial resistance (Gillespie, 2013) Improving antibiotic
stewardship by involving nurses http://www.sciencedirect.com/science/
VIEW PRESENTATION
article/pii/S0196655312008188

For example, a study by Du Toit et al in a South African hospital

reported on a nurse-led intervention implementing a checklist.
The intervention decreased excessive antibiotic duration,
increased compliance with cultures before antibiotics, and
optimised device removal (Figures 8, 9).
FIGURE 8
improvement in compliance with “duration of therapy”
FIGURE 9
Improvement in compliance with device removal
From: Du Toit, Briette (2015). The role of the critical care nurse in the implementation of an antimicrobial stewardship programme in a resource-limited
country. Thesis (MSc) --Stellenbosch University, 2015. http://hdl.handle.net/10019.1/98036

BARRIERS TO RESOLVE THE

PARTICIPATION OF NURSES IN
STEWARDSHIP TOOLKIT RESOURCE
Several barriers can affect the development, implementation PDF ARTICLE
and scale-up of antimicrobial stewardship roles for nurses.
Public Health England. 2015. Start Smart
Among these barriers we find:
Then Focus’
a) Ownership/’branding’
Despite the growing interest in the participation of nurses in

stewardship, frequently nurses do not recognise the potential In fact, some authors have proposed that ‘Good nursing care is
impact of their role in antimicrobial stewardship. If stewardship good stewardship, and good stewardship is good nursing care’
is suggested, it is possible that nurses express concern for the
tasks and care left undone due to staff shortages or workloads
of increased complexity. As such, nurses may also consider
that stewardship refers to appropriate prescribing, rather than CHA ANTIMICROBIAL
appropriate management of antimicrobials. Such ideas may drive
perceptions of inappropriateness and foster an unwillingness to
STEWARDSHIP: GOOD NURSING
participate in AMS activities (Cotta, 2014). IS GOOD STEWARDSHIP
Heard about Willing to WATCH VIDEO
AMS participate in AMS
Anaesthetists 38% 51%
Pharmacists 80% 100%
Physicians 64% 55% 'Good nursing care is good
Surgeons 37% 48% stewardship, and good stewardship
Nurses 22% 43% is good nursing care’
However, examining the recommended antimicrobial b) Educational barriers
management principles included in clinical guidelines such
as ‘Start Smart Then Focus’ (PHE, 2015) is helpful to identify Probably, nurses have difficulty identifying their role and
elements easily embedded in routine optimal care. involvement within stewardship due to the inadequate education
they receive on the topic at undergraduate level (Castro-Sánchez
et al, 2016). In essence, nurses do not know what they should do
as stewards and stewardship processes that are often less well
conducted (e.g. single-dose surgical prophylaxis or intravenous-
to-oral switch) appear to be even less frequently included in
course curricula.
This theory-practice gap is being resolved by implementing

education interventions targeting different settings. For example,
increased undergraduate nursing education about antimicrobials
in Scotland led to significant knowledge and attitude
improvements, which are likely to translate into positive clinical,
health and fiscal outcomes for patients and the health service.
FIGURE 9
Optimal antimicrobial management principles
WATCH VIDEO


TOOLKIT RESOURCE
SITE LINKS
Castro-Sánchez E, Drumright LN, Gharbi M, Farrell
S, Holmes AH (2016) Mapping Antimicrobial
Stewardship in Undergraduate Medical, Dental,
Pharmacy, Nursing and Veterinary Education in the
United Kingdom. PLoS ONE 11(2): e0150056
PDF ARTICLE
FIGURE 10 NHS Education for Scotland (2015) Antimicrobial
Antimicrobial stewardship principles by undergraduate discipline, UK Stewardship Educational Workbook
courses, 2013
From: Castro-Sánchez E, Drumright LN, Gharbi M, Farrell S, Holmes AH
(2016) Mapping Antimicrobial Stewardship in Undergraduate Medical,
Dental, Pharmacy, Nursing and Veterinary Education in the United
Kingdom. PLoS ONE 11(2): e0150056. https://doi.org/10.1371/journal.
pone.0150056
Finally, efforts to develop formal educational packages for

nurses have already crystallised into resources such as clinical
workbooks that aim to provide learning about antimicrobial
stewardship and support practice in this area (NES Scot, 2015).
Other initiatives have taken advantage of new technologies such

as smartphone applications (‘apps’) and, in collaboration with
end-user nurses, have co-designed nurse-specific guidelines
that reflect nurse interests and work requirements to increase
participation in stewardship (Wentzel et al, 2014). The impact
and sustainability of such approaches is yet to be established,
recognising that its use may not be feasible worldwide.

c) Leadership CONCLUSION
Whilst clinical nursing roles in stewardship appear to be Optimal antimicrobial stewardship efforts demand
increasing, there is still a need to engage with nurse leaders multidisciplinary approaches to retain impact and sustainability.
so they recognise the importance of the nursing contribution Although the participation of nurses in stewardship initiatives
towards stewardship efforts. Encouragingly, some nursing remains limited and focused on clinical aspects, there are
leaders are galvanising the debate about antimicrobial resistance emerging opportunities to expand these roles and involve
and AMS executives, leaders and policy-makers.
Learning from existing experiences from around the world

will help address some of the challenges associated with the
READ VIV BENNET'S implementation of this new sphere of practice for nursing
BLOG ENTRY professionals.
READ JO BOSANQUET’S
BLOG ENTRY
Building leadership capacity among stewardship nurses and

increasing the awareness about the threat of antimicrobial
resistance among nursing leaders has also been proposed as a
useful approach to ensure that nursing efforts in stewardship are
continued and effective.
VIEW IMPERIAL EVENT
FIGURE 11
1st International Nursing Summit on Antimicrobial Stewardship,
National Institute for Health Research in Healthcare Associated
Infection and Antimicrobial Resistance at Imperial College London

REFERENCES
Tackling Drug-Resistant Infections Globally: Final Report and Recommendations. The Review on Antimicrobial Resistance Chaired by
Jim O’Neill, May 2016 https://amr-review.org/sites/default/files/160525_Final%20paper_with%20cover.pdf
Castro-Sánchez E, Gilchrist M, McEwen J, Smith M, Kennedy H, Holmes A. Antimicrobial Stewardship: Widening the Collaborative
Approach. Journal of Antimicrobial Stewardship 2017; 1(1):29-37. Need link to this once published – DOI awaited
Cotta MO, Robertson MS, Tacey M, et al. Attitudes towards antimicrobial stewardship: results from a large private hospital in Australia.
Healthc Infect. 2014;19(3):89–94. doi: 10.1071/HI14008.https://www.researchgate.net/publication/273606907_Attitudes_towards_
antimicrobial_stewardship_results_from_a_large_private_hospital_in_Australia
Manning, M.L. The urgent need for nurse practitioners to lead antimicrobial stewardship in ambulatory health care. J Am Assoc Nurse
Pract. 2014;26:411–413. https://www.ncbi.nlm.nih.gov/md/?term=The+urgent+need+for+nurse+practitioners+to+
lead+antimicrobial+stewardship+in+ambulatory+health+care
Society for Healthcare Epidemiology of America and Infectious Diseases Society of America Joint Committee on the Prevention of
Antimicrobial Resistance: guidelines for the prevention of antimicrobial resistance in hospitals. Shlaes DM, Gerding DN, John JF Jr,
Craig WA, Bornstein DL, Duncan RA, Eckman MR, Farrer WE, Greene WH, Lorian V, Levy S, McGowan JE Jr, Paul SM, Ruskin J, Tenover
FC, Watanakunakorn C.
Infect Control Hosp Epidemiol. 1997 Apr;18(4):275-91. http://www.idsociety.org/uploadedFiles/IDSA/Guidelines-Patient_Care/PDF_

Library/Antimicrobial%20Resistance.pdf
Wentzel et al. Participatory eHealth development to support nurses in antimicrobial stewardship. BMC Med Inf and Dec Making 2014
14:45. https://bmcmedinformdecismak.biomedcentral.com/articles/10.1186/1472-6947-14-45
WHO, A universal truth: No health without a workforce, 2014

http://www.who.int/workforcealliance/knowledge/resources/hrhreport2013/en/
World Health Organization's World Health Statistics Report, 2011

http://www.who.int/whosis/whostat/2011/en/

CHAPTER 26
AUTHORS: DEBRA A GOFF & TIMOTHY GAUTHIER
THE ROLE OF THE

PHARMACIST IN
STEWARDSHIP
LEARNING OUTCOMES
CHAPTER IS TO:
• Explain how to work with a microbiologist to implement a rapid diagnostic test in
Define the role of an antibiotic the hospital setting
stewardship pharmacist.
• List some ways a pharmacist can provide advocacy for the responsible use of antibiotics
Describe eight key roles of • Define the different roles of the pharmacist in antibiotic stewardship
a stewardship pharmacist.
Provide examples of how

pharmacists perform each role.

CHAPTER 26 - THE ROLE OF THE PHARMACIST IN STEWARDSHIP
A pharmacist has multiple roles in an antibiotic stewardship PATIENT CARE

program. The Society of Infectious Diseases Pharmacists (SIDP)
and the American Society of Health-System Pharmacists (ASHP)
in the United State published a position paper highlighting
the importance of pharmacists with training in antimicrobial
stewardship in an effective antimicrobial stewardship program
(ASP). Ideally, every ASP pharmacist should have formal
infectious diseases (ID) training and maintain their ID skills
through continuing education and professional development.
The reality of having an ID-trained pharmacist at every hospital
presents a challenge. Certificate programs, online courses,
and eBooks are highly encouraged if more formal training is
not possible. In the hospital setting, pharmacists working from a centralised
pharmacy can make interventions such as IV to PO conversion,
The Centers for Disease Control (CDC) Core Elements renal dosage adjustments, therapeutic drug level monitoring
document states successful stewardship programs must have and review antibiotic durations of therapy. Pharmacists who
not only physician leadership and accountability but also drug participate in patient care rounds are able to perform these tasks
expertise from a pharmacist leader. We describe 8 core roles as well and are able to provide more advanced interventions
of an ASP pharmacist and provide real-world examples from including PK/PD optimisation based upon patient-specific factors
successful ASPs. and MIC of the organism and rapid de-escalation of therapy.

PDF ARTICLE PDF ARTICLE
Checklist for Core Elements of Hospital Antibiotic IV to PO Conversion: Quick Reference Guide for
Stewardship Programs Hospital Pharmacists
Core Elements of Antibiotic Stewardship in SITE LINK

Nursing Homes
Pharmacokinetics and Pharmacodynamics for
antibiotics: back to basics
The Essential Role of Pharmacists in Antimicrobial
Stewardship
Insights and Resources: Antibiotic renal dose
adjustments
SITE LINK
Core Elements of Outpatient Antimicrobial
Stewardship
Goff DA., Kullar R., Goldstein E et al. Lancet

Inf Dis 2017 Feb;17(2):e56-e63. doi: 10.1016/S1473-
3099(16)30386-3. A global call from five countries
to collaborate in antibiotic stewardship: united we
succeed, divided we might fail.

EDUCATOR B. Practice-based education

Teaching in the field is an important component in the learning
process. Pharmacists serve to cultivate drug knowledge for
trainees and providers. Since all specialties in healthcare
prescribe antibiotics, the role of the pharmacist in providing
education on the responsible use of antibiotics is critical.
C. Social Media for education

Social media is one forum that has attracted much attention as a
non-traditional mechanism for education. This includes platforms
such as Facebook, Instagram, Twitter, Figure1, and Youtube. In
these spaces pharmacists can connect with an audience in a
unique way, while providing meaningful resources or information.
One example comes from the @IDstewardship on Instagram,

authored by an infectious diseases PharmD with several years
of experience leading antimicrobial stewardship. His writing
Pharmacists provide education on antimicrobial stewardship consists of practical information for real-world use of antibiotics,
by sharing drug expertise knowledge within and external to the interviews with thought leaders, and fundamentals of infectious
pharmacy profession. Let’s look further into three categories of diseases pharmacotherapy
education…
A. Presentations
Within the classroom setting a common lecture for pharmacists
to give is on “bugs and drugs”, which focuses on clinical
infectious diseases pharmacotherapy. WATCH VIDEO


PDF ARTICLE PDF ARTICLE
Practical Guide to Antimicrobial Stewardship PDF of IDSA 2018 guideline [open access]
in Hospitals
SITE LINK SITE LINK

Antimicrobial Stewardship Online Training Course Wenzler E, Wang F, Goff DA et al. An Automated,
(British Society for Antimicrobial Chemotherapy and Pharmacist-Driven Initiative Improves Quality of
University of Dundee Care for Staphylococcus aureus Bacteremia. Clin
Infect Dis. 2017 Apr 4. doi: 10.1093/cid/cix315. [Epub
Development of Antimicrobial Competencies ahead of print]
and Training for Staff Hospital Pharmacists
[open-access] Goff DA, Bauer K, Mangino J. Bad bugs need old
drugs: a stewardship program's evaluation of
Review of Twitter for Infectious Diseases Clinicians: minocycline for multidrug-resistant Acinetobacter
Useful or a Waste of Time? [open-access] baumannii infections. Clin Infect Dis. 2014 Dec 1;59
Suppl 6:S381-7
Instagram and Clinical Infectious Diseases
[open-access] Bauer K, West J, Obrien J, Goff DA. Extended-
infusion cefepime reduces mortality in patients
with Pseudomonas aeruginosa infections.
Antimicrob Agents Chemother. 2013
Jul;57(7):2907-12
RESEARCH
Research is an important component of antibiotic stewardship.
The Infectious Diseases Society of America (IDSA) guidelines
RAPID DIAGNOSTIC TESTS
suggest ASPs implement interventions to improve antibiotic use
and clinical outcomes that target patients with specific infectious Rapid diagnostic tests (RDT) are game changing in the
diseases syndromes. This approach allows the message to be management of patients with infectious diseases. Several studies
focused, reinforces hospital specific guidelines, and is sustainable. have show that a RDT with ASP involvement shortens the time
Performing antimicrobial stewardship without collecting outcome to effective antibiotic therapy. Some studies have also shown a
metrics is a weakness of some ASPs. It is imperative to determine if mortality benefit. The key to successful implementation within a
ASP interventions provide meaningful impact on antimicrobial use, hospital is to make sure the microbiologist works with ASP. Studies
resistance rates, and patient outcomes. Pharmacist initiated ASP have show that when a RDT is made available without ASP, the
research can be done collaboratively with the physicians, nurses, results are not acted upon rapidly. This is a waste of financial
and microbiologists. Some examples of pharmacist initiated ASP resources and does not improve patient care. Pharmacists should
studies include work with the microbiologist to develop a strategy to receive the
RDT result prior to implementation. In a paper chart system where
• Disease based stewardship: An Automated, Pharmacist-Driven
significant delays can occur, the lab may need to page, text or
Initiative Improves Quality of Care for Staphylococcus aureus
phone the pharmacist. Hospitals with electronic records need to
Bacteremia.
determine the most efficient way to alert the pharmacist with the
• Evaluating a specific antibiotic: Evaluation of Minocycline for test result. The toolkit provides a RDT review article and several
Multidrug-Resistant Acinetobacter baumannii Infections studies that show how RDT plus ASP improves patient care.
• Pharmacokinetic-Pharmcodynamic dose optimization: Extended-

infusion cefepime reduces mortality in patients with
Pseudomonas aeruginosa infections.

Formulary decisions: Pharmacists play a part in hospital

antimicrobial formulary management. They help to decide which
TOOLKIT RESOURCE antibiotics should be on “protected status” to assure they are used
appropriately with ASP oversight
SITE LINK
Wenzler E, Wong J, Goff DA et al . Controversies
in Antimicrobial Stewardship: Focus on New HERE IS A BRIEF TEDX TALK ABOUT HOW
Rapid Diagnostic Technologies and Antimicrobials. PHARMACISTS ARE THE NEW “DISRUPTORS”
Antibiotics (Basel). 2016 Jan 14;5(1). pii: E6. doi:
IN HEALTHCARE, BECAUSE OF THEIR ROLE
10.3390/antibiotics5010006.
AS THE DRUG THERAPY EXPERT
Bauer K; Perez K; Forrest G; Goff DA. Review of
Rapid Diagnostic Tests Used by Antimicrobial
Stewardship Clin Infect Dis 2014 59 (8): S134-S145. WATCH VIDEO
Wenzler E., Goff DA., Mangino J., Reed R., Wehr A.,
Bauer KA. Impact of rapid identification of
Acinetobacter Baumannii via matrix-assisted laser
desorption ionization time-of-flight mass TOOLKIT RESOURCE
spectrometry combined with antimicrobial
stewardship in patients with pneumonia and/or
PDF ARTICLE
bacteremia. Diagn Microbiol Infect Dis. 2016 Extended-Infusion Cefepime Reduces Mortality in
Jan;84(1):63-8 Patients with Pseudomonas aeruginosa infection.
[open access]
Bauer K, West J, Balada-Llasat, Pancholi P.,
Stevenson K., Goff DA. An Antimicrobial
SITE LINK
Stewardship Program’s Impact with Rapid
Polymerase Chain Reaction Methicillin-Resistant Antimicrobial Stewardship Programs: A Review
Staphylococcus aureus/S. aureus Blood Culture for the Formulary Decision Maker [open access]
Test in Patients with S. aureus Bacteremia. Clin Inf
Dis 2010; 51(9):1074–1080
PATIENT SAFETY
Through individual action and by participating on inter-professional
DRUG THERAPY EXPERT teams, pharmacists are working to impact patient safety in the area
Pharmacokinetic/ Pharmacodynamic (Pk/PD) optimization: As of antimicrobial use.
drug therapy experts, pharmacists are able to develop treatment
In improving patient safety, pharmacists can be involved in:
plans that optimise PK/PD parameters. An important example of
where this comes into play is for beta-lactam infusions. The longer • Reporting medication errors
the period of time the concentration of drug is above the bacteria’s • Evaluating data from reported errors
minimum inhibitory concentration (MIC) at the site of infection,
the more bacterial killing. Through administering an intravenous • Participating in root-cause analysis
beta-lactam (e.g., cefepime) over 3 hours or 4 hours (rather than • Developing and implementing system-wide changes to
the standard 30 minutes), the amount of time the concentration is improve practices
above the MIC can be increased, thus improving bacterial killing.
• Participating in hospital committee work
This can positively impact the chances for a successful outcome.
Pharmacists are patient safety leaders and with antimicrobial
Therapeutic drug monitoring: Many antibiotics require
stewardship, their role extends from the medication management
therapeutic drug monitoring (e.g., vancomycin, aminoglycosides,
arena into other realms, such as infection control. One key example
voriconazole). In these instances the pharmacist’s familiarity with the
of this is with Clostridium difficile infection. In preventing and
medications plus their understanding of complex drug interactions
controlling this important pathogen, a combination of infection
can be invaluable.
control and prudent antimicrobial use is warranted.

TOOLKIT RESOURCE
PDF ARTICLE
Patient Safety Movement. Actionable Patient Safety
Solution (APSS) #3A: Antimicrobial Stewardship.
The Role of Pharmacy and the Microbiology Lab in
Patient Safety [open access]
SITE LINK
Institute for Safe Medication Practices Tools
and Resources
Institute for Safe Medication Practices Canada.

Ontario Antimicrobial Stewardship Project.
Preserving Antibiotics for Future Generations
Five Medication-Related Interventions Every

Pharmacist Should Know about Clostridium difficile
QUALITY CARE
Achieving quality in care aligns with antimicrobial stewardship
goals and some antimicrobial stewardship pharmacists are even
employees of the hospital quality department rather than the
hospital pharmacy department.
As new antimicrobial stewardship processes or services are

developed, continuous quality improvement monitoring may
be necessary. Through these monitors, enhancements can be
identified for further enhancing quality of care. As data from
monitors is produced, it can be reported to administration to
demonstrate the value of antimicrobial stewardship programs.
One study showed one in five inpatients treated with antibiotics

are harmed.
Internationally, antimicrobial stewardship standards are becoming

a component of quality measures. As this trend persists, the
pharmacists must engage quality officers to ensure compliance.
ADVOCACY
Pharmacists play an important role in advocating the responsible
use of antibiotics to healthcare providers, patients and consumers.
Advocacy can occur at Anytime, to Anyone, Anywhere. Remember
the 3A’s when you think of antibiotic advocacy. This 5 minute
podcast provides real-world examples for pharmacists on how to
advocate for the responsible use of antibiotics.

TOOLKIT RESOURCE DOWNLOAD SLIDE SET

PDF ARTICLE
Antimicrobial Stewardship Across 47 South To illustrate an example of a pharmacist advocating for the
African Hospitals: an Implementation Study responsible use of antibiotics you may wish to watch the
[open access] following 2 videos. Video one is from a TEDx talk by Debra Goff
PharmD titled “Antibiotics: just-in-case” As you watch the video
SITE LINK consider the following
National Quality Partners Playbook: Antibiotic • What is the predicted numbers of deaths from antibiotic
Stewardship in Acute Care resistant infection by 2050 if we just stay the course?
A Review of Quality Measures for Assessing the • What percent of antibiotics prescribed by doctors in US
Impact of Antimicrobial Stewardship Programs hospital have errors such as the wrong dose, wrong duration,
in Hospitals [open access] or even the wrong drug?
Australian Commission on Safety and Quality • How can a patient be an antibiotic steward while they are
in Healthcare: Antimicrobial Stewardship Initiative hospitalised?
Association of Adverse Events With Antibiotic

Use in Hospitalized Patients. Tamma et al TEDX TALK
Website with daily updates on antibiotic global
news, literature, meetings, research, article links, WATCH VIDEO
and podcasts
IDSA Guideline Implementing an Antibiotic

Stewardship Program This short 1 minute animated video with voice over, provides
an easy quick way to engage not only healthcare providers
in antibiotic stewardship but also consumers and patients.
It provides the user with a 1-minute elevator pitch on the
responsible use of antibiotics. As you watch the video think
of the following:
• After a colleague, patient, or friend watches the video

what type of discussion would you have with them?
• What are the key take aways from the video?
ANIMATED VIDEO
WATCH VIDEO

CHAPTER 27
AUTHOR: MICHAEL CORLEY
INFORMING & INFLUENCING:

STEWARDSHIP, POLITICIANS
& THE MEDIA
LEARNING OUTCOMES
THE AIM OF THIS
CHAPTER IS TO: On completion of this chapter, the participant should be able to:
• understand why engaging with politicians and journalists is so important to raising
Outline the benefits of engaging
awareness of AMS
with politicians and mainstream
media on issues relating to • appreciate the link between a dynamic community of research and practice and
antimicrobial resistance (AMR) and a culture of transparency and accountability
antimicrobial stewardship (AMS). • articulate why the need for public engagement has never been more urgent
Argue that a culture of transparency • outline the challenges of communicating clearly and responsibly
and public accountability can • list some of the resources that can aid clear and responsible communication
help to drive the creation and • engage confidently with a range of politicians and journalists
maintenance of a dynamic
community of research and practice
in AMR and AMS.
Demonstrate that the need for

“Never doubt that a small group of
public engagement on AMR and
AMS has never been more urgent.
thoughtful committed citizens can
Point to the challenges of
communicating clearly and
change the world. Indeed, it is the
responsibly to non-specialists on
AMR and AMS.
only thing that ever has.”
Margaret Mead, US Anthropologist (1901 to 1978)
Signpost to a few resources
that can aid clearer and more
responsible communication.
Though much of the information in this chapter can be applied universally, many of
Offer several ways in which
the references are to UK-based bodies and practices. This is only because it would
healthcare professionals and
have been impractical to try to account for differences between every media outlet,
scientists can engage with
voting chamber, or system of government. Instead, it is hoped that readers will adopt
mainstream media, new media,
and adapt the content to suit their own circumstances.
politicians, and the policymaking
process.

CHAPTER 27 - INFORMING & INFLUENCING: STEWARDSHIP, POLITICIANS, & THE MEDIA
GOING PUBLIC pointed to several dominant, but competing, discourses on the

subject: ‘AMR as healthcare’, ‘AMR as development’, ‘AMR as
Bringing about positive and sustainable change
innovation’, ‘AMR as security’ and ‘AMR as One Health’. Each has
Whether you call it campaigning, influencing, advocating,
its own scientific origin, conception of the problem, and method
networking, or giving voice, this chapter is focused on some
to prioritise action. Alone, they cannot account for the total
of the ways that we – both individually and collectively – can
complexity of the challenge.
bring about positive and sustainable change by engaging with
mainstream media and politicians. Getting the story straight
Wedded to the complexity of several competing discourses is
Like the first principle of open justice, good AMS must not
the phenomenon that more and more people want to involve
only be done; it must also be seen to be done. How else
themselves in the creation and delivery of the campaigns they
can best practice be extended and sustained if it is not first
support. This is understandable, and mostly desirable. But it
acknowledged, and a high value given to it by the public,
stands to reason that for each of us to be helped in our efforts
politicians, and the media?
we must all tap into an approach that is essentially coherent and
This principle also underpins the culture of transparency – cohesive. One of the quickest and easiest ways to do this is for
which is essential for learning, improving, and making each each of us to think about our audience when:
other accountable for the actions we take. Engaging with the
• Defining the problem
media and politicians, then, can help to raise good stewardship
to a level of consciousness that can drive the creation and • Outlining practical solutions
maintenance of a dynamic community of practice and research.
• Describing the part we play (or would like to play)
Responding to the urgent need • Deciding what language to use (e.g. technical,
And yet despite the undeniable benefits of raised awareness conversational, rhetorical)
almost all of the evidence suggests that the need for public
engagement on AMR has never been more urgent. • Bringing what we say to life with examples and illustrations
A 2015 survey by the World Health Organization across 12 • Linking our story to recent or forthcoming events
countries highlighted the lack of familiarity with the language of or developments
antibiotic resistance. • Issuing a clearly-defined ‘call to action’
Case study
Did the many headlines and discussions that followed the BMJ’s
VISIT SITE publication (July 2017) of Llewellyn et al’s opinion piece on when
it is appropriate to stop taking antibiotics, help or hinder the
public’s understanding of AMR and AMS?
A study by Wellcome Trust in the same year also found people

in the UK have little awareness of what ‘antibiotic resistance’
means and how it might affect their health. VIEW PUBLICATION
VISIT SITE
Even among healthcare professionals, AMR can mean different

things to different people. An article published by Wernli et al in
the BMJ in 2017
VIEW ARTICLE

It is, of course, a question of perspective. Debate is to be Communicating clearly and responsibly

welcomed – but what if it leads to more confusion than clarity? As Ben Goldacre points out in his book Bad Science,
BSAC’s take on the situation was published in the Guardian
soon afterwards.
BSAC’s reply, published in the Guardian (July 2017), to ‘The VIEW BOOK
antibiotics course has had its day’ article
many mainstream journalists do not have a scientific

background. Consequently, we must all take some responsibility
for working with newsgathering organisations to inform debate
and to report developments accurately and proportionately.
If you want to communicate research results to the public, you

might like to consider The Royal Society’s excellent guidance on
the subject: ‘Science and the public interest: Communicating the
results of new scientific research to the public’.
VIEW DOCUMENT


Accessing free information and educational resources the support of a campaign like Antibiotic Action (the public
In addition to your own research, there is a wealth of existing engagement arm of BSAC),
resources for you to draw upon when seeking to inform
and influence people outside of your own profession. The
Antimicrobial Resource Centre (ARC) was developed by BSAC
as a global repository of information for anyone interested in the VISIT SITE
effective management of infectious diseases.
or in the pledge to act as an Antibiotic Guardian. Politicians and

journalists rarely underestimate strength in numbers.
VISIT SITE
VISIT SITE
It includes a wide range of materials: videos, podcasts,
infographics, guidelines, images, press articles, publications,
research papers, slide sets, and systematic reviews.
To demonstrate the importance of cooperation, BSAC
As well as accessing content, users are encouraged to contribute produced a mini-manifesto, “Making Resistance Futile: Moving
it, so that we can all help to build a huge library that Antimicrobial Resistance Policy into Action”, that outlines why
is free to use anywhere in the world. authorities must find ways to engage learned societies and other
professional bodies, in local, national and international efforts to
combat resistance. Learned societies are a fundamental part of
the research, policy, service, and education landscape, providing
substantial intellectual, public and reputational benefit at a
negligible cost to the public purse.
MAKING RESISTANCE FUTILE

MOVING ANTIMICROBIAL
RESISTANCE POLICY
INTO ACTION
A Pan European Network Special Edition on behalf of the British Society for Antimicrobial Chemotherapy
with contribution from the European Society of Clinical Microbiology and Infectious Disease
Joining forces with others

The power of cooperation and collaboration is nowhere more
evident than through the membership of a professional body
like the British Society for Antimicrobial Chemotherapy (BSAC),
VISIT SITE

MAINSTREAM MEDIA distributed intentionally. Open letters usually take the form of
a letter addressed to an individual but provided to the public
Establishing contact with journalists
through newspapers and other media, such as a letter to the
Whether you choose to work with others or alone, there are
editor or blog. Especially common are critical open letters
always opportunities to promote an event or a development
addressed to political leaders.
via print and/or broadcast news. If you are keen on securing
your own coverage, the Media Trust has produced a short
introduction to writing a public relations plan. NEW MEDIA
Popularising the subject
Think of the success of high-profile scientists like Alice Roberts,
VISIT RESOURCE HUB Brian Cox, and Robert Winston, in communicating complex ideas
simply and powerfully. Many of these figures make the most of
new media to talk to people outside of the world of science.
If you intend to offer a story or yourself (as a spokesperson) start Blogging, vlogging and podcasts
by identifying all relevant health, science, and general news, Many new media outlets welcome ideas for blogs, vlogs,
reporters. A scan of articles published on AMR should yield a podcasts, and news articles. Here are just some of them for you
number of the names you need. Any good search engine will to consider subscribing and/or contributing to:
help you to do this.
HuffPost
Using case studies
Most journalists are trained to tell stories through the impact
they have on people. As such, it will pay for you to put lives at VISIT SITE
the heart of whatever it is you choose to say. Evidence can then
be used to show how typical or likely any given experience was.
Do you know anyone who has been directly affected by the

The Conversation
effects of AMR and who is prepared to share their experience
in a bid to educate or support others? Do you know of any
innovative practices that are having, or could have, a dramatic
impact in the lab or a healthcare setting?
VISIT SITE
Writing a letter to the editor
The subject matter of letters to the editor varies widely.
However, the most common topics include: BuzzFeed
• Supporting or opposing a stance taken by the publication

in its editorial, or responding to another writer's letter to
the editor
VISIT SITE
• Commenting on a current issue being debated by a
governing body – local, regional or national depending
on the publication's circulation. Often, the writer will urge ‘Comment is Free’ in the online Guardian
elected officials to make their decision based on his/her
viewpoint
• Remarking on materials (such as a news story) that have VISIT SITE

appeared in a previous edition. Such letters may either be
critical or praising
• Correcting a perceived error or misrepresentation. Reflections on Infection Prevention and Control
Issuing an open letter

These are intended to be read by a wide audience, or a letter
intended for an individual, but that is nonetheless widely
VISIT SITE

BSAC’s blog TED is a non-profit initiative devoted to spreading ideas, usually

in the form of short, powerful talks (18 minutes or less). It covers
almost all topics in more than 100 languages. Meanwhile,
VISIT SITE independently-run TEDx events help share ideas in communities

around the world.
Meeting up, listening in, speaking out VISIT SITE

There is a growing network of like-minded people who stage
open events (of varying sizes and levels of formality) to
demonstrate the appeal and relevance of science to the wider
world. They offer great opportunities to educate, inform, debate
– and even entertain – in a range of settings.
POLITICIANS
Lobbying public servants
Why not search online for details of events in your area. Among
Wherever you live, start by engaging your own elected
the most active networks in the UK are (nota bene: this list is by
representative(s). If you are based in his or her constituency
no means exhaustive):
they have an obligation to respond to you.
Café Scientifique is a place where, for the price of a cup of coffee
In the UK, you can find who represents you by visiting
or a glass of wine, anyone can come to explore the latest ideas
WriteToThem. As the name suggests, this site also provides an
in science and technology. Meetings take place in cafes, bars,
electronic letter-writing tool, with clear advice on how best to win
restaurants and even theatres, but always outside a traditional
the attention of the people who were elected to serve.
academic context.
Soapbox Science is a novel public outreach platform for

promoting women scientists and the science they do. Its events
transform public areas into an arena for public learning and
WHY HEALTHCARE
scientific debate. PROFESSIONALS SHOULD
ENGAGE WITH POLITICIANS AND
THE POLICYMAKING PROCESS
VISIT SITE
- KEVIN HOLLINRAKE MP
STEM Learning is the largest provider of STEM (science, WATCH VIDEO

technology, engineering, and mathematics) education and
careers support to schools, colleges and other groups working
with young people across the UK. Through partnership with Case study
Government, charitable trusts and employers, the Network is Do not assume that all politicians and/or policymakers are
dedicated to increasing the number of young people engaged in aware of the challenges wrought by AMR. Much can be
STEM-related studies and careers. achieved by simply offering to discuss your work with an elected
representative(s). For example, the UK’s Shadow Health Minister,
Julie Cooper, was deeply affected by a visit to the microbiology
team in a nearby hospital. She referred to this visit during a
VISIT SITE Westminster Hall Debate to mark World Antibiotic Awareness
Week 2017.

WHAT CAN MPS DO TO RAISE AN ISSUE IN

UK PARLIAMENT?’
MPs will have personal preferences on what methods
they use to raise a matter in the House. You can find more
information about each of the methods below at
www.parliament.uk or by requesting the relevant
factsheet from the House of Commons Information Office.
MPs can:
• Ask a Parliamentary Question of a particular Minister,
either written or oral
• Apply for an Adjournment Debate, during which
a Minister must give a response
• Introduce a Private Members’ Bill
“I recently met with microbiologists • Present a petition
at the Royal Blackburn Hospital • Table or sign an Early Day Motion (EDM)
and they were clear that urgent
action is needed to prevent the Linking up with All-Party Parliamentary Groups (APPGs)
inappropriate use of antibiotics. APPGs are informal cross-party groups that have no official
They were adamant: if we fail to status within Parliament. They are run by and for Members of the
Commons and Lords, though many choose to involve individuals
address this issue we are fast and organisations from outside Parliament in their administration
approaching a situation where even and activities.
the simplest routine operations will The benefits of these groups are listed as follows by Parliament’s
not be possible as we lose the fight website:
against infection. • A forum for cross-party interaction which is not controlled

by the whips
“Concerns about AMR are shared • A forum for interaction between parliamentarians in both
Houses
by MPs on all sides of the House
• A forum for parliamentarians, academics, business people,
and together we have a the third sector and other interested parties
responsibility to press the • A time and space for policy discussion and debate
Government to act. The question • A means for parliamentarians to set the policy agenda, which
is not whether we can afford to act is normally dictated by the front benches and in particular, by
but whether we can afford not to.” the Government's legislative priorities.
Here is a selection of APPGs that might be considered most

Julie Cooper MP for Burnley, Shadow Health Minister
relevant to our work:
Antibiotics (BSAC provides the secretariat for this Group)
VISIT SITE

Future Generations Personalised Medicine
Global Health Pharmacy
Health Primary Care and Public Health
Health in All Policies Scientific
Life Sciences Sepsis
Malaria and Neglected Tropical Diseases Staging an event

Holding an event can be a good way to launch a campaign or to
raise awareness of the work you are undertaking. If you would
VISIT SITE like to invite an MP to your event – or ask him or her to sponsor
an event in the Palace of Westminster – think carefully about
your aims.
• What value will they add to your event, and what would you
Patient Safety like to gain from their attendance?
• What will their role be?
• What will they get out of the event?
VISIT SITE • How does this fit with their specialist interests?
• Is this the best event to invite them to, or are you planning
another which might be more appropriate?

Checking the record Contacting representatives in the devolved administrations

Anyone can search Parliament’s publications and records. This If you live in Scotland, Wales, Northern Ireland or London,
portal includes open access to Hansard, which is the edited you also have at least one elected representative working
verbatim report of proceedings in both House. You can find out on devolved issues. In Scotland, Members of the Scottish
who said what and when, by searching these pages. Parliament (MSPs) represent local or regional constituencies,
as do Welsh Assembly Members in Wales and London
Assembly Members in London. In Northern Ireland, you have
one Northern Ireland Assembly Member to represent you.
VISIT SITE You can find out more by visiting: www.scottish.parliament.uk,
www.assemblywales.org, www.niassembly.gov.uk or
www.london.gov.uk.
Following Select Committee inquiries Monitoring the work of think tanks
Select Committees work in both Houses of Parliament. They A think tank, policy institute, or research institute is an
check and report on areas ranging from the work of government organisation that undertakes research and advocacy on topics
departments to economic affairs. The results of these inquiries such as social policy, political strategy, economics, military,
are public and many require a response from the government. technology, and culture. Most policy institutes are non-profit
Here are some of the Select Committees that could be organisations. Other think tanks are funded by governments,
considered most relevant to our work: advocacy groups, or businesses, or derive revenue from
consulting or research work related to their projects.
Education (Commons)
Here is just a selection of UK-based think tanks that specialise in
health and science policies:
VISIT SITE 2020health.org Grass roots independent think tank for health
and technology. Based in Westminster.
Environment, Food and Rural Affairs (Commons)

VISIT SITE
VISIT SITE
Institute for Public Policy Research The Institute for Public Policy
Research is the UK’s leading progressive think tank, producing
cutting edge research and innovative policy ideas for a just,
Health (Commons)
democratic and sustainable world.
VISIT SITE
VISIT SITE
Science and Technology (Commons)

Overseas Development Institute (ODI) ODI is Britain's leading
independent think tank on international development and
VISIT SITE humanitarian issues. ODI offers a fellowship scheme for

postgraduate economists to work in the public sectors of
developing countries in Africa
Science and Technology (Lords)

VISIT SITE
VISIT SITE

Reform Suggests improvements in the delivery of public services

and economic prosperity. Produce research of outstanding
quality on the core issues of the economy, health, education and
law and order. Based in Westminster.
VISIT SITE
The Bow Group Develops policy, publishes research, and

stimulates debate within the Conservative Party.
VISIT SITE
Responding to public consultations

Public consultations are part of a regulatory process by which
the public's input on matters affecting them is sought. Its main
goals are to improve the efficiency, transparency and public
involvement in large-scale projects or laws and policies. As the
title would suggest, anyone can respond.
You can search all UK Government consultations by keywords,

publication type, policy area, department, document status,
location, and publication date.
VISIT SITE
Signing up for Parliamentary alerts

Keep updated with political developments by signing up for
Parliamentary alerts via email. Simply select your areas of
interest when subscribing.
VISIT SITE

294 OUTCOMES
CHAPTER 1
OUTCOME 1: UNDERSTANDING BROADLY The impact of drug resistance infections compared to
WHAT ANTIBIOTICS ARE, HOW THEY WORK susceptible infection led to increased attributable cost, length of
AND THE BASIC MECHANISMS OF RESISTANCE stay, mortality and morbidity.
Antibiotics act against bacteria. They function by disrupting

OUTCOME 4: EXPLAIN THE CLINICAL AND
essential processes or structures in the bacterial cell. This either
kills the bacterium or slows down bacterial growth. Depending
ECONOMIC IMPACT OF DRUG RESISTANT
on these effects an antibiotic is said to be bactericidal or
INFECTIONS AND IMPACT ON HEALTH CARE
bacteriostatic. ACQUIRED INFECTIONS
Antimicrobial resistance is resistance of a microorganism to an In the USA majority of the 99,000 deaths due to health care
antimicrobial drug that was originally effective for treatment of acquired infections were due to drug resistant infections
infections caused by it. In the EU, the annual costs to society was Euro 1.56 billion and
In principal, there are three main antibiotic targets in bacteria: 600 million days of lost productivity
• The cell wall or membranes that surrounds the bacterial cell The impact of drug resistance infections compared to
susceptible infection led to increased attributable cost, length of
• The machineries that synthesizes the nucleic acids DNA stay, mortality and morbidity.
and RNA
• The machinery that synthesizes proteins (the ribosome OUTCOME 5: LIST SOME DEFINITIONS OF
and associated proteins) ANTIMICROBIAL STEWARDSHIP AND GOALS OF
Bacteria have two alternative pathways to acquire all types of STEWARDSHIP PROGRAMMES
resistance: Antimicrobial stewardship has been defined as “the optimal
• Random changes in the bacterial DNA (mutations) may selection, dosage, and duration of antimicrobial treatment
provide resistance by chance that results in the best clinical outcome for the treatment or
prevention of infection, with minimal toxicity to the patient and
• Alternatively, they can receive resistance genes from minimal impact on subsequent resistance.” It also can be defined
other bacteria nearby. This process is called horizontal as an “organizational or healthcare system wide approach to
gene transfer. promoting and monitoring judicious use of antimicrobials to
preserve their future effectiveness.
OUTCOME 2: OUTLINE THE DRIVERS The goals of stewardship are to improve patient’s outcomes,
FOR RESISTANCE increase patient safety, reduce resistance and optimise costs.
The excessive use and misuse of antimicrobial drugs accelerates Understanding and measuring any unintended consequences of
the emergence of drug-resistant strains, poor infection control stewardship, especially harm, is also an important goal.
practices, inadequate sanitary conditions and inappropriate food-
handling, poverty, lack or inadequate diagnostics tests, use and OUTCOME 6: IDENTIFY THE CORE ELEMENTS
misuse of antibiotics in agriculture and the environment, travel OF INFECTION CONTROL AND STEWARDSHIP
and other factors encourage the emergence and further spread PRACTICE AND THEN CONSIDER THEM IN THE
of antimicrobial resistance
CONTEXT OF A FICTITIOUS OUTBREAK OF A
DRUG RESISTANT HEALTH CARE ACQUIRED
OUTCOME 3: OUTLINE THE GLOBAL INFECTION.
EPIDEMIOLOGY OF KEY ANTIBIOTIC RESISTANT
PATHOGENS AND ANTIBIOTIC CONSUMPTION For the core components of an infection control and prevention
programme visit the following:
The global epidemiology of antibiotic consumption and
resistance through surveillance is patchy, not consistent or https://www.reactgroup.org/toolbox/prevent-infection/health-
uniform and not adequately delineated across the healthcare care/core-components/
settings. Areas of good practice are emerging.
For the core components of an antimicrobial stewardship
In the EU, the annual costs to society was Euro 1.56 billion and programme visit the following https://www.reactgroup.org/
600 million days of lost productivity toolbox/prevent-infection/health-care/core-components/

OUTCOMES
295
CHAPTER 2
OUTCOME 1: EXPLAIN CHANGES IN THE USE OUTCOME 4: DESCRIBE TRENDS IN ANTIBIOTIC
OF ANTIBIOTICS GLOBALLY AND WHAT IS USE IN HOSPITAL SETTINGS
DRIVING THIS CHANGE Around two thirds to three quarters of antibiotic use in high
Antibiotic use has been increasing globally. Over the period income countries is for the treatment of infections and up to one
2000-2010 overall use is estimated to have increased by fifth for surgical prophylaxis.
35% with broad spectrum pencillins and cephalosporins (the
There is a shift towards a greater use of broad spectrum agents
most commonly supplied antibiotics) increasing by 40%. This
with increases in 3rd and 4th generation cephalosporins,
increase has mainly been driven by factors such as economic
penicillin - β lactam inhibitor combinations and carbapenem use.
growth, increased expenditure on health and increased
In 2015 pencillin- β lactam inhibitor combinations and extended
access to antibiotics in middle income countries. Although
spectrum penicillins accounted for around 80% of penicillin use
high income countries continue to use the most antibiotics per
in European hospitals.
capita. Rising rates of antibiotic resistance and development
of multi drug resistant organisms is leading to increases in use The increasing presence of multidrug-resistant and extensively
of glycopeptides and reserve and last resort agents such as drug resistant organisms in ICU units is driving the use of
carbapenems and polymixins (e.g. colistin). glycopeptides and broad spectrum agents such as piperacillin
and tazobactam, 3rd and 4th generation cephalosporins,
cabapenems and agents of last resort such as colistin.
OUTCOME 2: DESCRIBE THE PREVALENCE AND
VOLUME OF ANTIBIOTIC USE IN COMMUNITY,
HOSPITALS AND LONG-TERM CARE AGED OUTCOME 5: DESCRIBE MISUSE OF ANTIBIOTIC
CARE SETTINGS AGENTS
The majority of antibiotic use, around 80%, occurs in the There are three areas of misuse
community where the percentage of the population prescribed underuse- mostly associated with lack of access to healthcare
an antibiotic use varies between countries. There is a four- services in low income countries
fold difference in volume of antibiotics used amongst OECD
countries. Use is highest in the young and the old, and is higher unnecessary use – an infection is not caused by a bacterium e.g.
in winter months where use is associated with inappropriate a viral infection, or where an antibiotic is not needed
treatment upper respiratory tract infections. inappropriate (or suboptimal) use – where timing, antimicrobial
There is a three-fold difference in volume of antibiotics used in choice, dose, route, frequency of administration or duration of
hospitals between high and low using countries in Europe with treatment is incorrect.
22% to 55% of inpatients prescribed one or more antibiotics.
More patients are prescribed antibiotics in ICUs and the rate of OUTCOME 6: LIST COMMON INDICATIONS
use is higher. WHERE ANTIBIOTICS ARE INAPPROPRIATELY
Antibiotic use in nursing homes is high and during the period of
PRESCRIBED/USED
a year 50 – 80% of residents will receive at least one course of In the community antibiotics are inappropriately prescribed for
systemic antibiotics. upper respiratory tract infections where over 50% of antibiotics
prescribed may be unnecessary. Up to 30% antibiotics use
OUTCOME 3: LIST THE MOST COMMON for asymptomatic bacteruria in nursing homes residents is not
ANTIBIOTIC AGENTS PRESCRIBED IN indicated.
COMMUNITY AND HOSPITAL SETTINGS In low income countries, antibiotics are often used
Penicillins are the most frequently used antibiotics in the inappropriately for diarrhoea and malaria.
community (making up 30 - 60% of use). Followed by In hospitals indications where antibiotics are commonly
cephalosporins, macrolides and quinolones with proportion and prescribed inappropriately include: surgical prophylaxis
volume of use varying considerably between countries. (especially excessive duration), respiratory infections (community
In some countries cephalosporins and other beta lactams acquired pneumonia, bronchitis) and urinary tract infections
(including carbapenem) are now prescribed more commonly in
hospitals than penicillins (including penicillin- β lactam inhibitor
combinations) followed by quinolones.

296 OUTCOMES
CHAPTER 2
OUTCOME 7: LIST THE KEY DRIVERS/
DETERMINANTS OF ANTIBIOTIC USE
• Attitudes, beliefs and social norms of the prescriber
• The organisational culture including the prescribing
“etiquette” set by senior medical staff based on autonomy
of decision making and a culture of medical hierarchy.
• Resistance not seen as a problem important in prescriber’s
own daily practice
• A lack of knowledge of local antimicrobial resistance, gaps
in antibiotic knowledge and/or awareness of local or national
prescribing guidelines.
• Diagnostic uncertainty
• Patients’ expectation of receiving an antibiotic and the
prescriber’s/suppliers perception of that expectation
• Reimbursement systems and marketing by the
pharmaceutical industry.
• Regulation of the supply of antibiotics

OUTCOMES
297
CHAPTER 3
OUTCOME 1: APPRAISE WHAT IS OUTCOME 2: EXPLORE OPPORTUNITIES FOR
ANTIMICROBIAL STEWARDSHIP AND WHAT IS IMPLEMENTING ANTIMICROBIAL STEWARDSHIP
PRUDENT ANTIMICROBIAL PRESCRIBING PROGRAMS IN ACUTE
Antimicrobial stewardship is defined (as previously presented
CARE HOSPITALS
in Chapter 1) as ensuring that every provider selects “The right This chapter has described opportunities to implement
antibiotic, for the right indication (right diagnosis), the right antimicrobial stewardship interventions such as
patient, at the right time, with the right dose and route, causing
• Optimal use of antibiotics for surgical prophylaxis
the least harm to the patient and future patients.” This definition
(selection and duration)
outlines the key principles of antibiotic prescribing. These
principles ensure that providers only prescribe antibiotics for • Reduce antibiotic consumption and costs without increasing
non-self-limiting bacterial infections. Antimicrobial stewardship mortality or infection-related re-admissions
programs create processes that promote prescribing that aligns
• Pertinent studies that demonstrate how stewardship
with the above definition. Additionally, the stewardship program
programs can optimise healthcare costs
takes responsibility for tracking and reporting prescribing and
resistance trends over time. • Describe the core elements of antimicrobial stewardship
programs with examples of areas where interventions could
Prudent antimicrobial prescribing ultimately leads to improved
be successfully implemented
patient safety, better clinical outcomes, cost-effective treatment,
reduction in toxicity and adverse events. There are many ways The U.S. Centers for Disease Control and Prevention have
that a stewardship program may ensure timely and appropriate established core elements necessary for developing a successful
antibiotic initiation. One way is to create clinical pathways that antimicrobial stewardship program. These core elements are as
direct prescribers toward appropriate antibiotics for specific follows:
disease states. These clinical pathways can either be built into
• Leadership Commitment: Dedicating necessary human,
the medical record software at the time of prescribing, or can be
financial and information technology resources.
available to prescribers via a manual or internet portal.
• Accountability: Appointing a single leader responsible for
In addition to timely and appropriate antibiotic initiation,
program outcomes. Experience with successful programs
stewardship programs may minimise risk for adverse events
show that a physician leader is effective
by implementing interventions for timely review or renal dose
adjustment. Timely de-escalation (being part of the review of • Drug Expertise: Appointing a single pharmacist leader
antibiotic prescriptions) will minimize patient exposure to broad responsible for working to improve antibiotic use.
spectrum antimicrobials and therefore reduce their risk for
• Action: Implementing at least one recommended action,
associated events such as resistance or C. difficile infection.
such as systemic evaluation of ongoing treatment need after
Renal dose adjustments will ensure patients are not over- or
a set period of initial treatment (i.e. “antibiotic time out” after
under-dosed which may increase their risk for adverse effects,
48 hours), IV to PO programs, prospective audit and
infection relapse, or development of resistance.
feedback, antibiotic restrictions, etc.
• Tracking: Monitoring antibiotic prescribing and resistance
patterns
• Reporting: Regular reporting information on antibiotic use and
resistance to doctors, nurses and relevant staff
• Education: Educating clinicians about resistance and optimal
prescribing

298 OUTCOMES
CHAPTER 3
OUTCOME 3: APPLY KEY PRINCIPLES OF
PRUDENT ANTIMICROBIAL PRESCRIBING IN
ACUTE CARE HOSPITAL SCENARIOS
Two clinical scenarios are presented to demonstrate how
antimicrobial stewardship programs can aid in prudent
prescribing. The toolkit has additional resources.
OUTCOME 4: DISCUSS POSSIBLE

UNINTENDED CONSEQUENCES OF
Process, outcomes and balancing measures are needed
to appropriate appraise the value and consequences of
antimicrobial stewardship. Balancing measures in particular
are needed to detect unintended negative consequences of
these interventions are fundamental to ensure that antibiotic
stewardship programs are safe. Healthcare systems, clinicians
and patients should be confident of the results and value of the
interventions.
In summary, this chapter highlights that we need to use our
resources wisely; “to widen access to appropriate medications
to encompass all people – regardless of race, gender, or socio-
economic status – while at the same time reserving these
precious compounds to treat only those diseases for which they
are specifically required.” We must all recognise the seriousness
of this problem and commit ourselves to using these precious
resources wisely balancing unintended consequences. ASPs
can help us identify such situations and avoid inappropriate
antimicrobial use. We have the means to ensure that our
antimicrobial armoury remains effective and that we preserve the
effectiveness of future antimicrobials in the pipeline

OUTCOMES
299
CHAPTER 4
OUTCOME 1: DESCRIBE KEY STEPS
IN DEVELOPING AN ANTIMICROBIAL
STEWARDSHIP PROGRAMME
A successful stewardship requires motivation, accountability
and leadership.
OUTCOME 2: IDENTIFY THE KEY

PERSONNEL WHO NEED TO BE INVOLVED
IN THE PROGRAMME
These include medical and pharmacy staff, but also nursing
staff and other specialties.
OUTCOME 3: OUTLINE SOME KEY ACTIVITIES

TO BE CARRIED OUT BY THE STEWARDSHIP
PROGRAMME
A business case may be necessary to get these staff
into service.
Every organisation will have barriers that will need to be
overcome to get a stewardship programme up and running.
OUTCOME 4: DESCRIBE SOME OUTPUT

MEASURES THAT CAN BE MONITORED FOR
THE PROGRAMME (FINANCIAL, GUIDELINE
COMPLIANCE, OUTCOMES - DECREASED
LENGTH OF STAY, ETC.)
The programme should have short, medium and long-term goals
and have governance and reporting/monitoring processes built
in – both to measure success and avoid harm.

300 OUTCOMES
CHAPTER 5
KEY MESSAGES FROM THIS CHAPTER
1. Develop strategies for measuring the process and outcomes
of your centre’s current stewardship activities.
2. Clarify the organisational structure and accountability of
your centre’s current stewardship activities.
3. Explore and document your center’s motivation to improve
antimicrobial stewardship in terms of its leadership and
dedication to the cause (measured in human and
financial capital).

OUTCOMES
301
CHAPTER 6
• If AMS programmes are ‘invisible’ in the organisational
structure in terms of programme implementation it is not clear
which resources are then available for these activities.
• In terms of governance, clear lines of accountability within
an organisation are critical. These accountability pathways
may be part of wider quality improvement or dedicated
to infection control and AMS. Either way these should
be identifiable.
• At the national level, action plans must identify the scope
and relevance of the various stakeholders, including capacity
building that may be required. Depending on the maturity
of the national action plan, a ground up approach can also be
employed by assessing this workforce and public
engagement at the programme level.
• Finally, by taking a view across the healthcare sector, use of
a framework to assess the level of integration of approaches
to AMS ensures that our strategies are line with patient
pathways as a well as the journey of organisms.

302 OUTCOMES
CHAPTER 7
OUTCOME 1: EXPLAIN WHAT EMPIRICAL OUTCOME 4: EXPLAIN WHY THE CLINICIAN
PRESCRIBING IS AND UNDERSTAND WHY NEEDS TO UNDERSTAND OPTIMAL USE OF
IT IS CURRENTLY PART OF NORMAL DIAGNOSTIC TESTS AND HOW THE RESULTS
DAY-TO-DAY PRACTICE COULD OTHERWISE BE MISLEADING
Empirical prescribing is where a prescription (in this case for The value of any diagnostic test is dependent on it being used
an antibiotic) is written before the cause of the illness is fully in the right way. The correct test must be performed in the
understood and is therefore a ‘best guess’ to cover the most correct context. Otherwise, the result might be misinterpreted
likely causes. Current diagnostic tests have a turn around time and lead to the wrong diagnosis and/or treatment. An example
that is too slow. Clinicians usually cannot or do not want to wait is the use of urine dipsticks (used for the diagnosis of urinary
until results are back before offering treatment. tract infection) in elderly patients, who are likely to have positive
results even in the absence of true infection.
OUTCOME 2: UNDERSTAND WHY EMPIRICAL
PRESCRIBING IS NOT IDEAL AND WHY OUTCOME 5: UNDERSTAND WHAT RAPID BIO-
IMPROVEMENT IN THE DIAGNOSIS OF MARKER TESTS ARE (E.G. C-REACTIVE PROTEIN
INFECTION ARE NEEDED AND PROCALCITONIN) AND HOW THEIR USE
Empirical prescribing means that patients get the prompt
COULD HELP SUPPORT ANTIMICROBIAL
antibiotic treatment that they need if they have a serious
PRESCRIBING DECISIONS
infection. However, it also means that they may receive C-reactive protein (CRP) and procalcitonin (PCT) are examples
unnecessary treatment if they do not have an infection, or may of acute phase proteins. Test values rise in the presence of an
receive an inappropriate antibiotic for the infection they have. inflammatory response and they have reasonable specificity for
bacterial infections.
Improvements to diagnostic tests are required to reduce turn
around times and, ideally, make each antibiotic prescription an These tests can be used to differentiate between bacterial and
informed prescription. viral infection and therefore identify some patients who might
not need any antibiotic treatment at all. They can also be used to
OUTCOME 3: EXPLAIN HOW THE monitor progress with treatment and help support a decision to
LABORATORY CAN SUPPORT ANTIMICROBIAL stop antibiotics.
STEWARDSHIP ACTIVITIES
Existing laboratory practices can facilitate antimicrobial
stewardship activities by providing results to clinicians in
a clinically useful timeframe. Laboratory accreditation and
other quality assurance activities make sure that results are
fit for purpose.
The introduction of laboratory automation and updated working
practices can make results available sooner. Newer technologies,
such as matrix assisted laser desorption ionisation time of
flight (MALDI TOF) mass spectroscopy to identify bacteria,
whole genome sequencing to interrogate the core genome
of the organism and internationally standardised antibiotic
susceptibility methodology to identify antibiotic resistance are all
changing diagnostic services dramatically.

OUTCOMES
303
CHAPTER 8
• Be familiar with common terminology pertaining to PKPD
underpinning antimicrobial use. This is most relevant to the
characteristics of the time-concentration curve and properties
of antimicrobials that dictate their killing action.
• Be aware of clinical situations that may dictate optimization
of dosing strategies out with standard dosing regimens.
Examples include critical illness, neonates, pregnancy
and obesity.
• Understand the complex issues of treating multi-drug
resistant bacteria, where PKPD properties are manipulated
by using combination therapy and altered drug dosing.
• Appreciate how PKPD can be applied to antimicrobial
stewardship, aiming to achieve optimal outcomes
while limiting the emergence of resistance and overuse
of antimicrobials.

304 OUTCOMES
CHAPTER 9
OUTCOME 1: BE AWARE OF THE TOOLS OUTCOME 3: UNDERSTAND WHERE
AVAILABLE TO CARRY OUT A BASELINE ANTIMICROBIAL STEWARDSHIP GROUPS FIT
ANALYSIS OF ANTIMICROBIAL STEWARDSHIP WITHIN ORGANISATIONAL STRUCTURES
WITHIN YOUR ORGANISATION A successful ASP should include clinical leadership and
Baseline checklists to assess current Antimicrobial Stewardship corporate responsibility. Clear lines of accountability to the
(AMS) practices can provide a useful gap analysis prior to executive team and governing bodies as well as other relevant
implementing an Antimicrobial Stewardship Programme (ASP). committees within the organisation need to be established in the
Useful resources are baseline checklists from CDC or NICE and development of an ASP. An example of where the antimicrobial
the Measurement for Improvement Toolkit from the Australian stewardship group lies within the organisational structure in a
Commission on Safety and Quality in Health Care. large multi-site teaching hospital is provided.
A proposed approach to implementing a successful ASP is:

OUTCOME 4: KNOW HOW TO IDENTIFY AREAS
• Collect baseline data within the organisation. WHERE ANTIMICROBIAL STEWARDSHIP
• Survey the AMS culture within the organisation. PROGRAMS SHOULD BE FOCUSED
• Assess the resources available to support an ASP. There is no “one size fits all” approach to ASPs and programmes
will vary according to the size and specialities provided
• Review existing antimicrobial guidelines and policies.
within the organisation. ASP should cover the whole of the
• Review communication within the organisation. organisation, however many centres are limited by the AMS
resources available. In such settings, priority areas for ASP
OUTCOME 2: RECOGNISE KEY PERSONNEL should be identified and targeted. Suggested priority areas are:
WHO SHOULD BE INCLUDED IN • Complex patients, i.e. ICU or acute admissions
ANTIMICROBIAL STEWARDSHIP GROUPS • Areas with high antimicrobial use
A successful antimicrobial stewardship group needs to
• Areas with high AMR rates
include the core members of the AMS team in addition to
representatives from clinical specialities within the organisation, • Areas with poor compliance to guidelines
for example:
Point prevalence surveys, surveillance of AMR, surveillance of
• A senior leader who has experience of implementing change antimicrobial use and benchmarking with peers should be used
to review priorities within an established ASP.
• Infectious diseases physician
• Antimicrobial pharmacist
• Microbiologist
• Nurse representatives
• Representatives from clinical specialities
• Infection control representative
• Drug and Therapeutics committee representative
• Primary care representative

OUTCOMES
305
CHAPTER 9
OUTCOME 5: DEFINE CORE AND ADDITIONAL OUTCOME 6: BE ABLE TO IDENTIFY MEASURES
INTERVENTIONS WHICH CAN BE EMPLOYED IN TO ASSESS THE EFFECTIVENESS OF
ANTIMICROBIAL STEWARDSHIP PROGRAMS ANTIMICROBIAL STEWARDSHIP PROGRAMS
Core interventions should form the basis of an ASP. Core Defined outcome measures should be defined as part of an
interventions include: organisations ASP strategy and used to assess the effectiveness
of the ASP. Suggested outcome measures include:
• Formulary restriction with re-authorisation of named
anti-infectives • Audit of compliance with guidelines.
• Prospective audit with intervention and feedback • Audit documentation – e.g. indication, stop/review date,
48-72-hour review.
• Multidisciplinary AMS team
• Audit time to 1st dose of antibiotic in sepsis.
• Guideline development
• Monitor antibiotic consumption data, including benchmarking
Additional interventions should then be considered for inclusion
to similar institutions.
in an ASP as resources allow with accordance with what is
appropriate within the individual healthcare setting. Additional • Monitor antibiotic expenditure data.
interventions include:
• Monitor stewardship interventions and acceptance rates.
• Review adverse events in relation to antimicrobials.
• De-escalation of therapy based on culture results
• Dose optimisation OUTCOME 7: RECOGNISE DIFFERENT
ROUTES OF COMMUNICATION WHICH
• Intravenous to oral switch
MAY BE USED WITHIN AN ANTIMICROBIAL
• Education STEWARDSHIP PROGRAM
• Antibiograms - at patient and organisation level There needs to be a clear plan on how to disseminate important
ASP messages to staff, for example ASP vision, updates to
• Information technology to provide decision support
guidelines, PPS results, AMR rates, infection outbreaks and
and enhanced surveillance
antimicrobial shortages. The proposed audience must be
• Antimicrobial order forms considered; what works in one setting may not work in another.
• Antimicrobial cycling Proposed communication routes include:
• Combination antimicrobial therapy • Posters in clinical areas / staffrooms

• Use of hospital intranet
• Organisational newsletter
• AMS newsletter
• Hospital-wide email
• Notifications via electronic prescribing programme or app
• Discussion at relevant hospital committees
• Screensaver / background on computers within the
organisation
• Email to divisional leads for dissemination in clinical areas
• Social media

306 OUTCOMES
CHAPTER 10
• Measurement is central to antimicrobial stewardship
• Through measurement you can you plan and prioritise
stewardship interventions.
• Measurement is essential to evaluate the impact if
stewardship interventions on clinical practice and
demonstrate benefits for patients.
• Measurement of the quantity and the quality of antibiotic
use are both needed.
• Focusing on data visualisation will enhance understanding
and engagement with the data.
• Without information feedback measurement alone will
not drive improvement.

OUTCOMES
307
CHAPTER 11
• There are some easy ‘quick wins’ that can be implemented
in any setting to improve antimicrobial use – start by looking
for ‘low hanging fruit’.
• Quality improvement methodology can be used to effect
change quickly on a small scale. There are many models but
all use key principles of having Will, Ideas and Execution.
• When applying quality improvement methods to antimicrobial
prescribing remember you need a clear aim and both process
and outcome measures.
• Collaborating with others working on stewardship through
a breakthrough collaborative can be helpful to share ideas
and learn from each other.
• Prescribing indicators are a simple tool for ongoing
assessment of antimicrobial use to monitor trends over time
and evaluate the impact of interventions, both intended and
unintended.
• Sharing local improvement data is the most important step in
the process to engage the clinical team and support
behaviour change.
• There are a variety of planning tools available to support
development and evaluation of stewardship interventions and
larger multi-faceted programmes.

308 OUTCOMES
CHAPTER 12
• Interventions designed to optimise antibiotic prescribing
in hospitals are more effective if they are designed to enable
prescribers by increasing their capability or opportunity to
follow policies.
• Currently few interventions use the most effective
enablement techniques of goal setting and feedback
combined with action planning.
• A better understanding of the contextual and social
determinants of antibiotic decision making in secondary care
is required in order to develop tailored interventions that
enable prescribers to optimise their decision making.
• To do this, we need to utilise the knowledge from social
science and improvement science research to try and
understand the context in which interventions work to
develop sustainable behaviour change.

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CHAPTER 13
OUTCOME 1: UNDERSTAND THE CURRENT OUTCOME 4: BE AWARE OF THE CORE
LANDSCAPE OF EDUCATIONAL COMPETENCES COMPONENTS OF EDUCATIONAL
FOR PRUDENT ANTIMICROBIAL PRESCRIBING COMPETENCES FOR PRUDENT PRESCRIBING
Of 145 countries responding to WHO’s questionnaire on
AND WHICH EDUCATIONAL RESOURCES
development and implementation off a national AMR action plan, COULD BE USEFUL IN THEIR LOCATION
only 12 countries did not have any training for it health workers. • Infection and antimicrobial stewardship in context: awareness
and interpretation of local and national antimicrobial usage
OUTCOME 2: DESCRIBE THE EDUCATIONAL and resistance data, national and international policy
STRATEGIES AVAILABLE FOR ANTIMICROBIAL pertaining to antimicrobial stewardship and global issues
STEWARDSHIP in AMR.
Educational strategies for antimicrobial stewardship can be • Clinical microbiology: theory, laboratory tests and their
passive or active. Examples of passive strategies include interpretation, clinical principles of infection and principles
distribution of printed antimicrobial prescribing guidelines, of AMR.
prescribing guidelines on organisation’s website, posters, • Antimicrobials: therapeutic drug monitoring, pharmacology,
handouts, conference attendance, staff/teaching sessions with pharmacokinetics and pharmacodynamics, and antimicrobial
minimal interactive sessions. Whilst active strategies include use in special populations.
focus groups for consensus-building, workshops, one-on-one
targeted sessions e.g. via academic detailing or educational • Management of clinical syndromes: organized by bodily system.
outreach by clinical educators (eg ID physician/microbiologist • Principles of an antimicrobial stewardship plan: role of the
or pharmacist). stewardship team and key components of hospital and
primary care stewardship programmes.
OUTCOME 3: DESCRIBE THE PROCESS FOR Several educational resources available from around the world
DEVELOPING COMPETENCIES have been provided in this chapter. They are not meant to be a
Competences should be developed using an evidence-based comprehensive list.
approach. One example of a step-wise approach taken to
develop competences is:
• Defining the target group/audience
• Review of the literature
• Review of existing competences and published curricula/
training objectives
• Synthesis of new competences
• Expert panel review and competency refinement using
eg Delphi methodology/expert consensus/workshop

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CHAPTER 14
• The prescribers and antibiotic stewards of tomorrow are
poorly prepared for the task and require better education and
training through improved undergraduate curriculae in LMICs.
• Much of the educational material developed by high income
countries and already in the public domain through the
internet is applicable to LMICs, but there is an increasing
amount of online material and tools available, which have
been developed in LMICs, that is directly applicable to low
resource settings.
• The high-income model of multidisciplinary antibiotic
stewardship teams of infection specialists needs to be
adapted and the essentials taught to non-specialist
prescribers, pharmacists, nurses and community
health workers.
• Different models of stewardship, which put pharmacists,
nurses and community health workers at the heart of the
stewardship response need to be developed in low resource
settings, in line with the health systems of those countries.

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CHAPTER 15
• In the US, pharmacists have an important role in applying
the results from a rapid diagnostic test to help improve
the time to effective antibiotic therapy in the management
of patients with S. aureus bacteremia.
• In Europe, antimicrobial stewardship initiatives have been
implemented for more than a decade in most countries,
and have used a variety of strategies.
• In GCC, Antimicrobial resistance is a global public health
threat. A strategic solution to stabilize or reduce microbial
resistance is implementing Antimicrobial Stewardship
Programs in healthcare settings. Gulf Cooperation States are
joining WHO global action plan in combatting resistance
• In Australia, comprehensive national guidelines, coordinated
national audit activities, and strong policy drivers have been
integral to the success of AMS programs.

312 OUTCOMES
CHAPTER 16
South Africa
• Successful stewardship programs can be implemented in
a variety of geographical and socio-economic settings by
health-care workers without formal ID training.
• Skills beyond infectious diseases are critical in initiating and
maintaining AMS programs.
• By focusing on a “vital few” antibiotic process measures such
as excessive antibiotic duration (> 7 or >14 days) or
prescription of antibiotics with overlapping or duplicate
spectra, can yield significant returns with the least effort.
• The creation of such alternative models for stewardship
that can be embedded within existing systems are dependent
on local context and resources but are key to success across
diverse settings
• Integral to success is collaborative cross-disciplinary
shared learning
India
• Sharing of hospital antibiogram & prescription auditing data
with prescribers results in a change in their prescribing
pattern, but the effect did not last for long
• For sustainable behavioural changes among prescribers,
continuous efforts in the form of prescription auditing along
with periodic focus group discussions would be a more
effective approach.
South America
• AMS involves healthcare system-wide approaches promoting
the judicious use of antimicrobials; this includes addressing
the regulatory environment. Despite the social and political
challenges, regulating over-the-counter sales has proven
effective in curbing self-medication with antibiotics. However,
efforts have to be sustained over time.
• Assessing antibiotic consumption levels, using sales data
converted into defined daily dose per 1000 inhabitants per
day (DDD/TID), is useful to raise leverage about addressing
the problem of antibiotic consumption in outpatient settings,
as well as to guide the implementation and evaluation of
interventions

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CHAPTER 17
OUTCOME 1: EXPLAIN THE UNIQUE FACTORS OUTCOME 4: REFLECT ON THEIR OWN
IMPACTING ON AMR AND AMS PRACTICE AND HOW TO INTRODUCE AMS
IN LTCF IN LTCF
Antimicrobial resistance patterns in LTCF are showing an For the core components of introducing AMS in your LTCF
increase in the rates of multidrug resistant organisms such as visit the following:
VRE, CRE and ESBLs. The nature of this setting, where isolation
https://www.cdc.gov/longtermcare/pdfs/core-elements-antibiotic-
facilities are often not available, contributes to this.
stewardship-appendix-b.pdf
The elderly LTCF population are at increased risk of infection,
with sometimes serious consequences, which can drive high
rates of antimicrobial prescribing.
Unlike the secondary care setting, LTCFs often do not have an
AMS strategy due to lack of on-site multidisciplinary teams to
drive this agenda.
OUTCOME 2: TO UNDERSTAND THE FACTORS

INFLUENCING THE PRESCRIBING OF
ANTIMICROBIALS IN LTCF
Antimicrobial prescribing in LTCF is influenced by many factors
unique to the setting, especially the frail population, the lack of
on-site diagnostic and microbiological resources, and doctors
are primarily off-site.
Misinterpretation of urine dipsticks can lead to overprescribing of
antibiotics for urinary tract infections.
OUTCOME 3: IDENTIFY AND COMMUNICATE

THE CORE GOALS OF A LTCF AMS STRATEGY
Antimicrobial stewardship in LTCF must be developed and
implemented with a locally appropriate and relevant strategy.
The strategy must examine on the rate of antimicrobial
prescribing and also the choices of antimicrobials prescribed,
with a focus on local or national prescribing guidelines.
The strategy must also examine the interpretation of urinary
dipsticks and urinary catheter care.
Infection Prevention and Control policies and procedures must
adhere to national standards to prevent the spread of infection
or outbreaks.
The strategy should be feasible, using readily accessible data to
benchmark antimicrobial resistance and prescribing data against
local or national data.

314 OUTCOMES
CHAPTER 18
OUTCOME 1: IMPORTANCE AND OUTCOME 4: ICU ANTIMICROBIAL
OPPORTUNITIES OF ICU ANTIMICROBIAL STEWARDSHIP OUTCOME MEASURES
STEWARDSHIP • Ascertaining and reporting on “appropriateness” of therapy
• An overwhelming majority of patients in ICUs receive holds the greatest promise for evaluating antimicrobial
antimicrobials, with high associated costs. stewardship interventions.
• ICUs environments often contain drug-resistant infections. • De-escalation and patient outcomes?
• Optimizing use of antimicrobials addressed antimicrobial • Consumption and cost metrics are useful secondary
use and costs, minimizing antimicrobial selection pressure. measures, but lack the clinical context of “appropriateness”.
• Balancing measures and antimicrobial resistance are
OUTCOME 2: STRUCTURES NEEDED FOR important considerations in evaluating antimicrobial
ANTIMICROBIAL STEWARDSHIP IN THE ICU stewardship in the ICU.
• ICU ASPs require external “coaches”, preferably with
infectious diseases expertise (i.e. infectious diseases
physician or pharmacist, or a microbiologist).
• An interprofessional team will bring the most varied and
holistic approach to antimicrobial stewardship.
• Optimising antimicrobials in the ICU requires timely and
reliable information:
• Antibiograms – preferably ward-specific, and weighted-
incidence syndromic antibiograms (WISCA)
• Accurate, up-to-date report of patient’s clinical status,
microbiology information, and recent and current
antimicrobial therapy
OUTCOME 3: THE BEST INTERVENTIONS TO

STEWARDSHIP ANTIMICROBIALS IN THE ICU
• Coaching, or prospective audit with feedback, appears to
be the best approach to stewarding antimicrobials in the ICU.
• Ensuring diagnostic tests for infection are necessary, valid
and reliable (diagnostic stewardship) will reduce unnecessary
antibiotic treatment.
• ICU prescribers benefit from antimicrobial guidance
directed to empiric therapy, preferably based on local
resistance patterns.
• De-escalation or simplifying antibiotics is another way
ICU prescribers can benefit from stewardship

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CHAPTER 19
OUTCOME 1: DEFINE AN OUTCOME 4: IDENTIFY THE OPPORTUNITIES
IMMUNOCOMPROMISED HOST FOR AMS IN IMMUNOCOMPROMISED HOSTS
A wide-range of conditions can result in immune-compromise The most commonly included AMS activities implemented in this
including primary immunodeficiency, diseases such as advanced patient setting include:
diabetes and HIV, severe malnutrition and drug-induced
• Formulary review and restriction
immune compromise, such as during the treatment of cancer,
inflammatory conditions or post-transplantation. • Guideline development
These patients have a reduced ability to immunologically • Prospective audit and feedback
respond (or at all) to an infection.
• Education
OUTCOME 2: EVALUATE THE ROLE OF NET • Dose optimisation

IMMUNOSUPPRESSION IN MEDIATING THE RISK
OF INFECTIONS IN SUSCEPTIBLE HOSTS OUTCOME 5: DISCUSS THE ROLE OF MULTI-
DISCIPLINARY WORKING IN DELIVERING AMS
The net state of immunosuppression can vary considerably
between patients and there is intra-patient variability over time. To work effectively there should be close collaboration between
Although assessing a patient’s net state of immunosuppression the AMS team and the HIV, cancer or transplant teams with
can be challenging, it is useful in assessing what infections the a shared appreciation of the complexities of caring for these
patient may be at risk of and what level of investigation and patients. Success requires an open MDT approach and
antimicrobial intervention is therefore justified. collaborative development of guidelines.
OUTCOME 3: DESCRIBE BARRIERS TO OUTCOME 6: LIST CONSIDERATIONS FOR

AMS IN THE IMMUNOCOMPROMISED ANTIMICROBIAL TREATMENT IN THIS SPECIAL
PATIENT SETTING PATIENT POPULATION
• Difficult to diagnose infections – invasive diagnostics • Must be timely: delay in initiation potentially increases
and less commonly used blood tests may be required to mortality
confirm infection • Appropriate: must cover the suspected pathogen(s) – these
• Broad spectrum of infections: Need to differentiate may not just be bacteria BUT also viruses and/ or fungi need
between colonisation and active infection; MDROs are to be considered
common due to repeated and prolonged broad-spectrum • Administered at optimal dosing – taking consideration of
antimicrobial courses PK-PD and drug-drug interactions
• Prescriber perception and attitudes – patients are deemed • Prompt de-escalation/ discontinuation when practical
‘sicker’ and / or ‘special-cases’ compared to immune-
competent patients
• Inaccuracy with antibiotic allergy labelling can drive
inappropriate agent choice
• Need for timely treatment

316 OUTCOMES
CHAPTER 20
OUTCOME 1: RATIONAL ANTIMICROBIAL
PRESCRIPTION FOR SURGICAL PROPHYLAXIS
The selection of antimicrobial would depend on the type of
surgery. Usually, a single first-generation cephalosporin for
operations not expected to encounter anaerobes or a single
second-generation cephalosporin with anaerobic operations
based on local susceptibility patterns is sufficient. It has to be
administered 60 minutes prior to surgery or for antimicrobials
like Vancomycin it should be administered 120 minutes.
Repeat dose is recommended only for surgeries lasting more
than 4 hours.
OUTCOME 2: ADHERENCE TO GUIDELINES

It is very important to adhere to Institutional surgical prophylaxis
guidelines. If the institution doesn’t have one, then it is
mandatory to comply with International guidelines released by
organizations such as WHO, CDC, SHEA etc.
OUTCOME 3: UNDERSTANDING
PHARMACOKINETICS/PHARMACODYNAMICS
OF RECOMMENDED SURGICAL PROPHYLAXIS
Understanding basic pharmacokinetics of surgical prophylaxis
is very essential. It is especially important because redosing
of the antimicrobial depends on a pharmacokinetic parameter
named” biological half-life”. The biological half-life of a
substance is the time it takes for a substance to lose half of its
pharmacologic, activity. Intra operative redosing is recommended
only for procedures that exceed two half-lives
of the antimicrobial used for surgical prophylaxis.

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CHAPTER 21
OUTCOME 1: UNDERSTANDING WHAT AFS IS OUTCOME 4: UNDERSTANDING THE
Antifungal stewardship can be defined as ‘the optimal selection,
DIFFERENT WAYS ANTIFUNGALS ARE USED
dosage, and duration of antifungal treatment that results in the Antifungal agents are used to prevent infections in some
best clinical outcome for the treatment or prevention of infection susceptible patients (i.e. prophylaxis).
with minimal toxicity to the patient and minimal impact on
They can also be used empirically in a susceptible patient who
subsequent resistance’.
has clinical evidence of infection and is not improving with an
antibacterial agent, so is presumed to have a fungal infection.
OUTCOME 2: UNDERSTANDING SOME BASIC
MEDICAL MYCOLOGY For a diagnosis of proven IFI, specimens must be obtained
by a sterile technique from a normally sterile site. Invasive
Medically important fungi capable of causing invasive fungal mould infection is proven if hyphae are seen in a histological or
infection can be broadly split into three categories; yeasts (e.g. cytological specimen or a mould is grown in culture from that
Candida spp. and Cryptococcus spp.), moulds (e.g. Aspergillus specimen with clinical or radiological evidence of infection at
spp. and the zygomycetes) and dimorphic fungi (e.g. Histoplasma the site from which the specimen was taken. Systemic yeast
spp.). infection would be proven on the same evidence as above or if
Candida albicans is the most commonly isolated strain of the yeast was grown in a blood culture. A diagnosis of probable
Candida. Invasive candidiasis is the most common fungal IFI requires a combination of host factors and microbiological
disease among hospitalised patients in the developed world. and clinical criteria, whereas a diagnosis of possible IFI requires
Invasive aspergillosis is a major cause of invasive mould host factors and clinical features.
infection and tends to affect the immunocompromised. Treatment decisions therefore depend on:
Antifungal resistance is well recognized and has been associated • Host factors
with antifungal exposure.
• Clinical features
OUTCOME 3: UNDERSTANDING SOME OF THE • Microbiology results

BENEFITS OF AFS
AFS programmes have been associated with:
OUTCOME 5: UNDERSTANDING HOW TO
START AN AFS PROGRAMME
• reducing inappropriate antifungal use
It is important to understand antifungal use in your patient
• cost savings due to the high cost of many antifungals population. Audit and surveillance can be helpful to identify
• improved patient outcomes (e.g. mortality) challenges or poor practice. It can also be used to persuade
clinical and managerial colleagues of the need for AFS and
With the rise of antifungal resistance in recent years, AFS is likely provide data to assess the efficacy of future interventions. A
to be important in mitigating further emergence of antifungal good starting point is to create or review guidelines and clinical
resistance. pathways in line with local epidemiology and patient population.
The availability and turn-around-time of diagnostics should be
considered within this process.

318 OUTCOMES
CHAPTER 22
• Discussing antibiotic decisions with parents in terms of severe
versus non-severe infections is more likely to be effective
than an explanation based on the distinction between
bacterial and viral infections.
• It is extremely difficult for clinicians to reliably distinguish
bacterial and viral respiratory tract infections and there
are few reliable diagnostic tests available in community
based settings. Unfortunately, this uncertainty often results
in clinicians prescribing “just in case”, despite the availability
of good evidence demonstrating that antibiotics make little
or no difference to the speed of symptoms resolution in most
children with bacterial RTIs.
• Decisions about whether to prescribe antibiotics in children
with RTIs should be made using evidence based guidelines.
• Clinicians should be provided with up to date information
on the management of common infections in children within
a robust education programme. Priority should be placed
on ensuring that consistent approaches to management
are adopted across community and front of house hospital
settings (emergency department/paediatric assessment
unit). Inconsistent prescribing practices impact on future
health seeking behaviour and antibiotic expectations.
• Parent satisfaction remains high, even when no prescribing
or delayed prescribing approaches are adopted, as long as
parent concerns have been addressed during the
consultation.
• Antimicrobial stewardship is an extremely effective way
of improving antibiotic prescribing within hospital settings.

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CHAPTER 23
OUTCOME 1: DESCRIBE KEY ELEMENTS OUTCOME 4: LIST EXAMPLES OF CHALLENGES
OF A MULTI-DISCIPLINARY OPAT BUNDLE CENTRAL TO THE OPAT-STEWARDSHIP
Key elements of a multi-disciplinary OPAT bundle as outlined in
DILEMMA DESCRIBED BY GILCHRIST AND
figure 1 include the following actions: COLLEAGUES
• Initial selection of the appropriate antibiotic regimen • It is challenging to select a narrow spectrum OPAT regimen
with a convenient dosing schedule, which does not require
• Monitoring for clinical response and tolerability, and adjusting frequent dose adjustment or laboratory monitoring.
doses as needed
• A prime example is the selection of once daily IV ceftriaxone
• Selecting the most feasible discharge regimen in terms of for methicillin susceptible S. aureus (MSSA) treatment rather
cost, drug stability and compatibility with IV access than IV nafcillin or oxacillin.
• Determining the timing of IV to PO switch
• Providing education on infection risk factors, treatment goals
and expectations
• Determining when to stop antibiotics at clinical cure or clinical
failure, if the later is due to surgical disease
OUTCOME 2: OUTLINE DISTINCT MODELS OF

OPAT CARE DELIVERY
Distinct OPAT care models can be adapted to available
resources, staff, geography, and patient access to care. Briefly,
these are:
• Centralised, office or hospital-based infusion centres
• Home-based programs utilizing specialized infusion and
nursing teams
• OPAT care within skilled-nursing facilities
OUTCOME 3: DESCRIBE UNIQUE CHALLENGES

TO OPAT IN DIFFERENT PARTS OF THE WORLD
• Underserved populations in need of OPAT care exist
throughout the world, from the urban poor of New York City
to rural communities in Canada
• Studies suggest that standardization of OPAT care delivery in
Asia is still needed

320 OUTCOMES
CHAPTER 24
OUTCOME 1: DISCUSS REASONS WHY CDSSS OUTCOME 4: TO DISCUSS THE ISSUES THAT
ARE REQUIRED BOTH FOR PRESCRIBERS AND MAY IMPACT ON THE UPTAKE OF THESE
FOR AMS SYSTEMS INTO CLINICAL PRACTICE
Decision support is required for prescribers as antibiotic Data overload and alert fatigue is a potential problem, and the
prescribing decisions are complex, and rely on multiple patient importance of triaging workflow needs to be emphasised.
and infection factors. Decision-making around antimicrobial
Successful implementation of CDSSs depends on a number
prescribing necessitates review of a large amount of information.
of factors, including the speed and usability of the system; the
Factors to consider include signs and symptoms of infection,
extent to which it has been successfully integrated into the
likely pathogens, treatment options, and potential drug
workflow; the clarity of recommendations and interventions; the
interactions, contraindications and adverse reactions.
availability of evidence and justifications for recommendations;
Inappropriate prescribing is common the monitoring of impact and clinician feedback; incentives for
use; and local adaptation of guidelines.
CDSSs can support better decision making by enabling access
to patient information, enforcing compliance with antimicrobial
policies and procedures, and driving evidence-based prescribing.
Management and review of large clinical workloads can be
streamlined through use of CDSSs. Audit processes can be
enhanced through CDSSs. AMS can use CDSSs to provide
restrictions and approvals, to monitor prescribing behaviours,
to efficiently triage patients who require post-prescription review,
and to assist with reporting and feedback.
OUTCOME 2 & 3: DESCRIBE THE FEATURES

OF CDSSS THAT SUPPORT ANTIMICROBIAL
PRESCRIBING. COMPARE AND CONTRAST
THE DIFFERENT TYPES OF CDSSS
Different types of CDSSs facilitate different functions and
operations, and prioritise different kinds of information.
Online clinical portals containing guidelines enable clinicians to
access and use recommendations at the point of care.
Antimicrobial approval and authorisations systems support
formulary control and indication restrictions facilitate. They
facilitate auditing of antimicrobial use (particularly when
combined with post-prescription review) and feedback to
prescribers.
Infection prevention and surveillance systems can help identify
bug-drug mismatches and generate alerts to help identify
patients who are at risk of developing nosocomial infections.
Advanced decision support systems can provide decision
support by helping identify potential infections, pathogens and
treatment options based on inputs about patient symptoms and
other information.

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CHAPTER 25
OUTCOME 1: WHY SHOULD NURSES BE Reflect on emerging activities in nursing homes and long-term
INVOLVED IN ANTIMICROBIAL STEWARDSHIP? care facilities that would benefit antimicrobial stewardship
initiatives.
• Describe drivers for participation of nurses in antimicrobial
stewardship activities. • Nurses can avoid measures that have limited or no clinical
benefit yet can trigger antimicrobial prescriptions, such as
• Shortages in human resources worldwide and increased routine urine sampling.
demands on antimicrobial stewardship programmes
encourage the involvement of nurses in stewardship.
OUTCOME 4: INTEGRATION BETWEEN
NURSING ROLES AND ACTIVITIES IN AMR AND
OUTCOME 2: EXPANDING THE PARTICIPATION OTHER PROFESSIONALS
OF NURSES IN ANTIMICROBIAL STEWARDSHIP
Understand the areas for antimicrobial stewardship synergy and
• Identify how antimicrobial documents and policies consider integration between nurses and other professionals.
nursing participation in stewardship.
• Establishing the allergy status of a patient; timely initiation
• Guidelines such as ‘Start Smart Then Focus’ or the European of antimicrobials; monitoring therapeutic drug levels; adhering
Commission Guidelines for the Prudent Use of Antimicrobials to optimal infection prevention and control practice, etc.,
in Humans recognises the participation of nurses in could be collaborative roles.
antimicrobial stewardship initiatives.
Explain antimicrobial stewardship clinical tasks that could be OUTCOME 5: STEWARDSHIP, A TARGET
adopted by nurses. FOR NURSES IN EXECUTIVE AND
Typical roles for nurse participation in stewardship include DIRECTIVE POSITIONS
clinical areas such as ensuring that adequate biological samples Discuss how nurses in executive and directive positions
are obtained before instigation of antimicrobials; evaluation of can contribute to and strengthen antimicrobial stewardship
clinical response and discussion of de-escalation; and patient programmes.
education, among others.
• Engaged board members and managers could have an
Consider the impact in antimicrobial usage of advanced nursing impact on stewardship initiatives similar to that achieved in
roles such as prescribing. hand hygiene or infection prevention and control
Prescribing nurses are bound by existing prescribing guidelines. programmes, patient safety and quality improvement.
The volume of antimicrobials prescribed by nurses around the
world continues to increase. OUTCOME 6: NURSE-FOCUSED
INTERVENTIONS IN ANTIMICROBIAL
OUTCOME 3: PUBLIC HEALTH AND STEWARDSHIP
COMMUNITY NURSING CONTRIBUTION TO Reflect upon some existing nurse-centred stewardship
ANTIMICROBIAL STEWARDSHIP interventions.
Critically argue some public health nursing behaviours that could • Some studies emphasising nursing education achieved
be embedded within antimicrobial stewardship frameworks. improvements in intravenous-to-oral switches and discussions
• Nurses could reduce the demand for antibiotics in primary about the need for continued intravenous antibiotics as well
care by influencing public and patient knowledge and as increased participation in stewardship activities, decreased
expectations of antibiotic prescribing through their societal excessive antibiotic duration, increased compliance with
contacts; Leading and implementing immunisation cultures before antibiotics, and optimised device removal.
programmes across all age groups to prevent avoidable
infection and associated morbidity and mortality; Leading
and implementing public health strategies to support the
public to ‘live well’ and prevent or reduce the burden of long
term conditions such as diabetes, liver disease, obesity.

322 OUTCOMES
CHAPTER 25
OUTCOME 7: BARRIERS TO RESOLVE THE
PARTICIPATION OF NURSES IN STEWARDSHIP
a. Examine some barriers for increased involvement of nurses
in stewardship.
• Ownership, education and leadership
b. Evaluate existing initiatives implemented to address barriers
to nurse involvement.
• ‘Good nursing care is good stewardship, and good
stewardship is good nursing care’. Education interventions,
including resources such as clinical workbooks and new
technologies such as smartphone applications (‘apps’),
targeting different settings have led to significant
knowledge and attitude improvements.
• Building leadership capacity among stewardship nurses
has been the focus of nursing meetings and summits.

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CHAPTER 26
OUTCOME 1: EXPLAIN HOW TO WORK WITH OUTCOME 3: DEFINE THE DIFFERENT
MICROBIOLOGIST TO IMPLEMENT A RAPID ROLES OF THE PHARMACIST IN ANTIBIOTIC
DIAGNOSTIC TEST IN THE HOSPITAL SETTING STEWARDSHIP
Rapid diagnostic tests (RDT) are game changing in the Pharmacists have many different roles in different parts of the
management of patients with infectious diseases. The key to world. This can vary from the traditional role of drug dispensing
successfully implementing RDT includes good communication (South America) to being credentialed to prescribe antibiotics
between the microbiology lab and the antibiotic stewardship (US). Pharmacists in all settings can apply their drug expertise to
pharmacists or physician. assure patients receive the correct antibiotic at the correct dose
and duration and de-escalate when appropriate.
The stewardship pharmacists should work with the
microbiologist to develop a strategy to receive the RDT result Pharmacists can provide more advanced interventions including
prior to implementation of the RDT. PK/PD optimisation based upon patient-specific factors and MIC
of the organism.
OUTCOME 2: LIST SOME WAYS A PHARMACIST Rapid diagnostic tests can be implemented with antibiotic
CAN PROVIDE ADVOCACY FOR THE stewardship pharmacists intervention to assure time to effective
RESPONSIBLE USE OF ANTIBIOTICS antibiotic therapy is maximized.
Pharmacists play a key role in advocacy of appropriate antibiotic Research is an important role for stewardship pharmacists. More
use. Advocacy can occur at Anytime, to Anyone, Anywhere. data is needed to show the impact of antibiotic stewardship
on patient outcomes and antibiotic resistance. Designing
Pharmacists can engage in a discussion about antibiotics
stewardship interventions as a study that can be published
with patients, consumers, and other healthcare professionals.
helps teach the world in addition to advancing the profession of
Discussion points should include how antibiotics are societal
pharmacy.
drugs that impact everyone.
Pharmacists can help to link antibiotic stewardship interventions
Pharmacists can volunteer to speak about the responsible use
to both quality and patient safety.
of antibiotics to healthcare providers, students, community
organizations, and school children.

324 OUTCOMES
CHAPTER 27
OUTCOME 1: UNDERSTAND WHY ENGAGING • Many mainstream journalists do not have a scientific
WITH POLITICIANS AND JOURNALISTS IS SO background.
IMPORTANT TO RAISING AWARENESS OF AMS
OUTCOME 5: LIST SOME OF THE RESOURCES
Whether you call it campaigning, influencing, advocating,
networking, or giving voice, we can bring about significant and
THAT CAN AID CLEAR AND RESPONSIBLE
sustainable change by engaging with mainstream media and
COMMUNICATION
politicians. If you want to communicate research results to the public, you
might like to consider The Royal Society’s excellent guidance on
AMS must not only be done; it must also be seen to be
the subject: ‘Science and the public interest: Communicating the
done. Best practice will only be extended and sustained if it
results of new scientific research to the public’.
is acknowledged, and a high value given to it by the public,
politicians, and the media. In addition to your own research, there is a wealth of existing
resources for you to draw upon when seeking to inform
OUTCOME 2: APPRECIATE THE LINK BETWEEN and influence people outside of your own profession. The
A DYNAMIC COMMUNITY OF RESEARCH AND Antimicrobial Resource Centre (ARC) was developed by BSAC
PRACTICE AND A CULTURE OF TRANSPARENCY as a global repository of information for anyone interested in the
effective management of infectious diseases. It includes a wide
AND ACCOUNTABILITY
range of materials: videos, podcasts, infographics, guidelines,
Effective public engagement helps to create a culture of images, press articles, publications, research papers, slide sets,
transparency – which is essential for learning, improving, and and systematic reviews.
making each other accountable for the actions we take.
OUTCOME 6: ENGAGE CONFIDENTLY WITH A
OUTCOME 3: ARTICULATE WHY THE NEED FOR RANGE OF POLITICIANS AND JOURNALISTS
PUBLIC ENGAGEMENT HAS NEVER BEEN MORE
The power of collaboration is nowhere more evident than
URGENT through the membership of a professional body like the British
• A 2015 survey by the World Health Organization across 12 Society for Antimicrobial Chemotherapy (BSAC), the support
countries highlighted the lack of familiarity with the language of a campaign like Antibiotic Action (the public engagement
of antibiotic resistance arm of BSAC), or in the pledge to act as an Antibiotic Guardian.
Politicians and journalists rarely underestimate strength in
• A study by Wellcome Trust in the same year also found
numbers.
people in the UK have little awareness of what ‘antibiotic
resistance’ means and how it might affect their health There are always opportunities to promote an event or a
development via print and/or broadcast news. The Media
• Even among healthcare professionals, AMR can mean
Trust has produced a short introduction to writing a public
different things to different people. An article published by
relations plan.
Wernli et al in the BMJ in 2017 pointed to several dominant,
but competing, discourses on the subject: ‘AMR as Also, think of the success of high-profile scientists like Alice
healthcare’, ‘AMR as development’, ‘AMR as innovation’, Roberts, Brian Cox, and Robert Winston, in communicating
‘AMR as security’ and ‘AMR as One Health’. Each has its complex ideas simply and powerfully. Many of these figures
own scientific origin, conception of the problem, and method make the most of new media to talk to people outside of the
to prioritise action. world of science.
Wherever you are based, start by engaging your own elected
OUTCOME 4: OUTLINE THE CHALLENGES OF representative. If you live in his or her constituency they have
COMMUNICATING CLEARLY AND RESPONSIBLY an obligation to respond to you. There are many ways in which
• AMR is at the heart of several competing discourses a public servant can raise issues and/or lobby for change,
inside and outside whichever voting chamber and/or system
• More and more people want to involve themselves in the of government they have been elected or appointed to serve.
creation and delivery of the campaigns they support
• We need to develop a campaigning approach that is
essentially coherent and cohesive

EDITOR IN CHIEF & AUTHOR: CHAPTER 1 AUTHOR: CHAPTER 2
DILIP MARGARET
NATHWANI DUGUID
Professor DILIP NATHWANI
Margaret Duguid has over 30 years experience in the
MB, FRCP (London & Ed), DTM&H, OBE
quality and safety of medicines use as a pharmaceutical
Co-Director Academic Health Sciences Partnership [AHSP]
advisor and hospital pharmacy manager. Most recently Margaret
in Tayside, Consultant Physician in Infectious Diseases and
was the Pharmaceutical Advisor at the Australian Commission
Honorary Professor of Infection, Ninewells Hospital and Medical
on Safety and Quality in Health Care (the Commission) where
School, Dundee
she was involved in national initiatives promoting the safe
Dilip qualified from Aberdeen University in 1984, and has and quality use of medicines and antimicrobial stewardship.
subsequently training in internal medicine/infection/tropical Margaret served on the Commission’s Antimicrobial Stewardship
medicine in Aberdeen, Glasgow and Birmingham, UK. Since Advisory Committee for a number of years and in 2011 she co-
2014 he is the Co-Director of the AHSP in Tayside, the first of its edited the commission’s publication Antimicrobial Stewardship
kind in Scotland and with the primary aim of enabling innovation for Australian Hospitals.
across the health and social care sector. He also has been the
recent [2008-2017] Chairman of Scottish Government Funded
Scottish Antimicrobial Prescribing Group (SAPG). SAPG is a
national clinical antimicrobial stewardship programme. Chair of
the European Study Group on Antibiotic Policies [ESGAP] from
2011–14 and President of the British Society for Antimicrobial
Chemotherapy [BSAC]; Recent National Specialty Adviser
for Infectious Diseases to the Scottish Government Health
Department; External advisor on Antimicrobial Stewardship
& Education Policy to a number of professional societies,
governments and non-UK governmental bodies including WHO;
Programme director of the first Massive open on line course
[MOOC] on Antimicrobial stewardship. In 2015 he was awarded
the Order of the British Empire [OBE] by Her Majesty the Queen
for outstanding services to the treatment of Infectious Diseases.
Dilip has authored more than 250 peer reviewed publications
and has a range of local, national and international contributions
to research & innovation in the domains of education, quality
improvement, guidelines and policy, particularly in the field
of antimicrobial stewardship. He also has been interested in
outcomes research and value based healthcare.

AUTHOR: CHAPTER 3 EDITOR & AUTHOR: CHAPTER 3
ELIZA LILIAN
DOLLARD ABBO
Eliza Dollard received her Doctor of Pharmacy from the Dr. Lilian M Abbo, is a board certified infectious diseases
University of Connecticut School of Pharmacy in 2014. physician, expert in the management of transplant
She completed her Pharmacy Practice and Infectious Diseases associated infections and multidrug resistant organisms, and
residencies at Jackson Memorial Hospital in Miami, Florida. After the Chief for Infection Prevention and Antimicrobial Stewardship
residency she became the Pediatric Infectious Diseases Clinical at Jackson Health System. Dr. Abbo has direct responsibility
Pharmacist at Holtz Children’s Hospital, associated with Jackson and authority for the strategic assessment and implementation
Health System, where she resided until 2017. She now lives in of programs to prevent healthcare associated infections and
Portland, Maine where she serves as the Pediatric Infectious monitor the appropriate use of antimicrobials in an extremely
Diseases Clinical Pharmacist for Barbara Bush Children’s large, complex system that deals with an incredible range of
Hospital and the Health-System Antimicrobial Stewardship patient populations and clinical conditions. She also frequently
Clinical Pharmacist for MaineHealth. works with the hospital system’s communications team to
address the local and national news media and community
groups about infectious disease, antimicrobial stewardship, and
other public health matters.
Dr. Abbo obtained her medical degree from the Universidad
Central de Venezuela, “Luis Razetti” Medical School followed
by a fellowship in Infectious Diseases at Jackson Memorial
Hospital/ University of Miami. She has co-authored over 70
peer-reviewed publications, 3 book chapters and more than 80
abstracts in the fields of antimicrobial stewardship, transplant
associated infections and infection prevention. She is a co-
author of the 2016 Infectious Disease Society of America (IDSA)
Guidelines for the Implementation of Antimicrobial Stewardship
Programs in Acute Care Hospitals.
Lilian is a Fellow of the IDSA, she also serves several national
and international committees for IDSA, the Society of Healthcare
Epidemiology of America and the American Society of
Transplantation. She been an invited speaker in more than 35
international and over 100 regional/ local oral conferences. Lilian
is the course director for the British Society for Antimicrobial
Chemotherapy (BSAC) Massive online education course “Gram
negative infections” available in future learn. Her research grants
are in the areas of antimicrobial resistance and stewardship. She
has received several awards from the University of Miami for her
leadership in diversity and for her work in the advancement of
women in academia and healthcare.

EDITOR & AUTHOR: CHAPTER 4 AUTHOR: CHAPTER 5
CONOR PAUL
JAMIESON POTTINGER
Conor Jamieson is the Pharmacy Team Leader for Dr. Pottinger is an Associate Professor of Infectious
Antimicrobial Therapy at Sandwell and West Birmingham Diseases at the University of Washington in Seattle, USA.
NHS Trust in Birmingham, UK. He graduated from Aston He co-directs the Antimicrobial Stewardship Program at UW
University with a first class honours in Pharmacy in 1996 and was Medical Center with Rupali Jain, PharmD. Together, they partner
awarded a PhD in Microbiology by the same institution in 2002. with medical providers to improve the use of anti-infective
Since then he has been working in clinical practice in the NHS in medications for the complex and heterogeneous patient
the field of antimicrobial stewardship. He was formerly Honorary population there. He directs the hospital’s clinical ID section, and
Treasurer of the British Society of Antimicrobial Chemotherapy, the ID & Tropical Medicine Clinic. He is also Associate Director
having previously served as a council member of the Society, of the ID Training Program, where his efforts focus on optimising
and is the current chair of the Drug Stability Testing Working the fellows’ clinical training experience.
Party for BSAC

AUTHOR: CHAPTER 6 AUTHOR: CHAPTER 6
ALISON RAHEELAH
HOLMES AHMAD
Professor Alison Holmes FMedSci is a Professor of Raheelah Ahmad PhD FHEA FRSPH
Infectious Diseases at Imperial College London and Health Management Programme Lead within the
has a longstanding clinical and research career in the field of faculty of Medicine at Imperial College London at the National
infectious diseases with particular interests in antibiotic use, Institute for Health Research (NIHR) Health Protection Research
antimicrobial resistance and public health, particularly in the Unit for Healthcare Associated infections and Antimicrobial
context of acute care. Resistance. Raheelah is leading research to evaluate sustained
impact of interventions across the healthcare economy
Alison is Director of the National Institute for Health Research
to address antimicrobial resistance (NIHR Fellowship in
Health Protection Research Unit in Healthcare Associated
Knowledge Mobilisation). Her research to evaluate public
Infections and Antimicrobial Resistance at Imperial College
health interventions at the system and organisational level
London and holds various awards as Principal or Co-
from provider and user perspectives, has attracted consistent
Principal Investigator on a range of multidisciplinary research
funding in the UK and internationally (ESRC, NIHR, World Bank,
programmes.
Global Fund and DIFD). Current research includes investigating
She leads a large multi professional and multi-disciplinary antibiotic use along surgical pathways (England, Scotland,
research group and network, with strong collaborations both Rwanda, India & South Africa). Raheelah completed her Masters
nationally and internationally. in Health Services Management at LSHTM, doctorate in Health
Management at Imperial’s Business School and BSc (hons) in
Within the NHS, she is Director of Infection Prevention and
Mathematics at UCL. She is also Senior Associate Editor for the
Control and an Associate Medical Director, as well as a
international peer reviewed journal Public Health.
consultant in infectious diseases.

NICHOLAS ALASDAIR
BROWN MACGOWAN
Dr Nicholas Brown MBChB MA MD FRCP Alasdair MacGowan is Lead Public Health Microbiologist
(London) FRCPath for Public Health England in the South West, Professor
of Antimicrobial Therapeutics at the University of Bristol, and
Nick Brown is a Consultant Medical Microbiologist at
Consultant in Infection at North Bristol NHS Trust. He has led a
Addenbrooke’s Hospital in Cambridge and an Associate Lecturer
mixed NHS academic research group in the area of antimicrobial
at the University of Cambridge. He is employed by Public Health
chemotherapy for over twenty years, and provides medical
England (PHE) and is currently interim Lead Public Health
input into the National Antibiotic Assay Reference Laboratory at
Microbiologist for the East of England. He is the immediate past
Southmead Hospital. He has a research interest in antibacterial
President of the British Society for Antimicrobial Chemotherapy
pharmacokinetics/dynamics, rapid diagnostics and antimicrobial
(BSAC).
resistance in the community. He holds a Programme Grant on
Nick has a career long interest in the use of antibiotics and management and diagnosis of Blood Stream Infection from NIHR
antibiotic resistance. He was recently appointed Director of the England, has a Research for Patient Benefit Grant on antibiotic
Antibiotic Action initiative of the BSAC. He is also a member of optimisation to prevent emergence of resistance, is Work
various groups working on the implementation of the strategy to Package Lead in an EU FP7 Programme Grant on resurrecting
combat antibiotic resistance, including diagnostic stewardship. old antibiotics, and is part of two IMI funded academic consortia
involved in various aspects of drug development. At present,
active grants total >£20m. He is a former President of the British
Society for Antimicrobial Chemotherapy (BSAC), chairs the
BSAC Standing Committee on Antimicrobial Resistance
Surveillance and is UK representative on European CDC Expert
Committee EUCAST.

AUTHOR: CHAPTER 8 EDITOR & AUTHOR: CHAPTER 9
MELISSA MARK
BAXTER GILCHRIST
Melissa qualified from the University of Aberdeen Mark Gilchrist MPharm MSc (IPresc) FFRPS FPharmS
Medical School in 2011, achieving the MBChB degree Mark is Consultant Pharmacist Infectious Diseases &
with honours. Having completed postgraduate foundation Stewardship at Imperial College Healthcare NHS Trust.
rotations in Cornwall she is currently a training registrar in
He is a council member of British Society of Antimicrobial
Medical Microbiology and Virology in the Southwest Peninsula
Chemotherapy and co-chairs its UK OPAT Initiative. He is an
Deanery. She enjoys training in all aspects of bacteriology and
senior honorary lecturer at Imperial College London, together
in particular orthopaedic and soft tissue infections. Interests
with being a spokesman on antimicrobials and fellow of the
outside of work include cycling, surfing and kayaking.
Royal Pharmaceutical Society.
Mark has particular interests in antimicrobial stewardship around
improving systems and processes that affect local, national
and international AMR. His clinical interests include OPAT,
tuberculosis and critical care.
Postgraduate education includes an MSc and non-medical
independent prescribing status and he was recently awarded
the NHS Leadership Academy Nye Bevan Award in executive
healthcare leadership. He is immediate past chair of the UK
Clinical Pharmacy Association - Pharmacy Infection Network
(UKCPA PIN) and was awarded RPS Faculty Fellowship
(Infection) in 2013.
He has delivered many lectures and workshops on AMS both
at national and international level and has published around
his areas of interest. He was a member of the working group
that reviewed and developed the 2015 Public Health England
“Start Smart then focus” stewardship toolkit and co-authored the
UKCPA/RPS Faculty infection curriculum. Mark was a tutor on the
global massive open online course on AMS and is an editor for
Pharmacotherapy and Journal of Antimicrobial Stewardship.

ORLA WILLIAM
GEOGHEGAN MALCOLM
Orla Geoghegan is lead pharmacist, infection at William Malcolm is Pharmaceutical Advisor in Health
Imperial College Healthcare NHS Trust. Her postgraduate Protection Scotland (HPS), part of NHS National Services
qualifications include an MSc in clinical pharmacy and a Scotland. HPS is responsible for the planning, coordination and
certificate in independent prescribing. Orla is a member delivery of specialist health protection activities to protect all the
of the Royal Pharmaceutical Society and UK Clinical people of Scotland from infectious and environmental hazards.
Pharmacy Association.
As a member of the Scottish Antimicrobial Prescribing Group
(SAPG), a national clinical multi-disciplinary forum that leads the
national antimicrobial stewardship programme, William leads the
national surveillance programme for antibiotic use in humans in
Scotland. William is a firm believer in the ability of informatics
as a driver for optimization of antibiotic use to improve patient
outcomes and minimize harm in patients with and at risk from
infection.

JACQUELINE ESMITA
SNEDDON CHARANI
Dr Jacqueline Sneddon is Project Lead for the Scottish Esmita Charani MPharm, MSc, MRPSGB
Antimicrobial Prescribing Group (SAPG), a national clinical Esmita is the Senior Academic Pharmacist within the
multi-disciplinary forum that leads the national antimicrobial faculty of Medicine at Imperial College London at the NIHR
stewardship programme. Jacqueline holds a Pharmacy degree Health Protection Research Unit for Healthcare Associated
from Heriot-Watt University, a PhD in Medicinal Chemistry and Infections and Antimicrobial Resistance. She is also a visiting
MSc in Clinical Pharmacy both from the University of Strathclyde. Researcher at Haukeland University Hospital, Bergen Norway,
She is a Fellow of the Faculty of the Royal Pharmaceutical where she is involved in helping implement that national
Society (RPS) and Chair of the UK Clinical Pharmacy Association antibiotic stewardship programme. She is currently completing
(UKCPA) Pharmacy Infection Network. her doctoral thesis investigating antimicrobial stewardship
across India, Norway, France and England. She is the co-
Within SAPG Jacqueline has led development of education
developer or a Massive Open Online Course on antimicrobial
resources on antimicrobial stewardship, prescribing quality
stewardship with the University of Dundee and BSAC.
indicators, development of national consensus on antimicrobial
policies and initiatives to improve the use of antimicrobials She is the recipient of the RPSGB Galen Pharmacy Research
in Care Homes and recently development of a national Award for research into antibiotic dosing and obesity and
antimicrobial app. She was a tutor on the global massive open an investigator in a NIHR Invention for Innovation award
on-line course on Antimicrobial stewardship and was a topic investigating the development and use of a point of care
expert for the NICE guideline on Antimicrobial stewardship: personalised clinical decision support tool for antimicrobial
changing risk-related behaviours in the general population. prescribing. The focus of her research has been behaviour
change interventions and the role of mobile health technologies
to influence decision making. She is co-investigator on the
ESRC award (2017-2021): Optimising antibiotic use along
surgical pathways: addressing antimicrobial resistance and
improving clinical outcomes (in England, Scotland, Rwanda,
India & South Africa). Esmita completed her Masters (MPharm
Hons) in Pharmacy at University College London, and her MSc in
Infectious Diseases at LSHTM.

PETER DIANE ASHIRU-

DAVEY OREDOPE
Peter Davey MD FRCP, Professor, Medical School Lead for Dr Diane Ashiru-Oredope is the Lead Pharmacist for
Healthcare Improvement. Population Health Sciences the Antimicrobial Resistance Programme at Public Health
Division, Medical School, University of Dundee England. An antimicrobial pharmacist by background; she
started working in public health in 2010 as part of the Health
Peter is the Medical School Lead for Healthcare Improvement at
Protection Agency. She has chaired and led the implementation
the University of Dundee. He trained as an Infectious Diseases
of a range of national toolkits and guidance on antimicrobial
Physician in Birmingham UK and at the Tufts New England
stewardship (AMS). Over the last nine years, Diane has led
Medical Centre in Boston. He joined the University of Dundee
the development, implementation and evaluation of the
in 1989 on a University Grants Committee Clinical Senior
national AMS toolkit Start Smart then Focus, the national
Lectureship to work on record linkage in the fields of antibiotic
antimicrobial prescribing and stewardship competences as
prescribing and healthcare associated infection. He is past
well as the international AMR campaign, Antibiotic Guardian
President of the British Society for Antimicrobial Chemotherapy.
which is underpinned by behavioural science. Currently she is
He was awarded the Garrod Medal by BSAC in 2015 for his
the deputy chair for the English Surveillance Programme for
contribution to improving prescribing of antibiotics.
Antimicrobial Utilisation and Resistance (ESPAUR) and leads
the national planning group for World Antibiotic Awareness
Week, European Antibiotic Awareness Day and the UK Antibiotic
Guardian campaign  Outside of her core role, Diane is on the
editorial board for the Journal of Antimicrobial Chemotherapy,
honorary Lecturer at UCL School of Pharmacy, volunteer tutor
for the People’s University which delivers public health Masters
courses/modules for healthcare professionals in low and middle
income countries, committee member for UKCPA Pharmacy
Infection Network, member of Royal Pharmaceutical Society
(RPS) Expert Advisory Group for Antimicrobial Resistance and
adviser for Commonwealth Pharmacists Association.

AUTHOR: CHAPTER 14 AUTHOR: CHAPTER 15 & 24
MARC ARJUN
MENDELSON RAJKHOWA
Marc Mendelson is Professor of Infectious Diseases and Dr. Arjun Rajkhowa is the centre manager of the National
Head of the Division of Infectious Diseases & HIV Centre for Antimicrobial Stewardship, based at the Peter
Medicine at Groote Schuur Hospital, University of Cape Town Doherty Institute for Infection and Immunity at the University
(UCT). He studied Medicine at St Mary’s Hospital, London and of Melbourne and Royal Melbourne Hospital in Melbourne,
specialized in Infectious Diseases at Addenbrookes Hospital, Australia. He is a qualitative researcher whose interests include
Cambridge, where he attained his PhD. He moved to The policy, public health and communications.
Rockefeller University, New York in 2001 and subsequently to
UCT to work on tuberculosis and innate immunity.
Marc is Chair of the South African Ministerial Advisory
Committee on Antimicrobial Resistance, the South African lead
for Antimicrobial Resistance on the Global Health Security
Agenda, co-chair of the South African Antibiotic Stewardship
Programme, and co-author the South African Antimicrobial
Strategic Framework. He is on a number of WHO technical
advisory panels relating to antibiotic resistance, is a member of
the scientific advisory group of the Global Antibiotic Research
and Development Partnership (GARDP), and a member of the
AMR Core Team of the World Economic Forum/Wellcome Trust
collaboration on implementing new models of antibiotic R&D.
He is Past-President of the Federation of Infectious Diseases
Societies of Southern Africa, and President-Elect of the
International Society for Infectious Diseases.

EDITOR & AUTHOR: CHAPTER 15 AUTHOR: CHAPTERS 15 & 26
CÉLINE DEBRA
PULCINI GOFF
Céline Pulcini is Full Professor of Infectious Disease in Debra A. Goff, Pharm.D., FCCP, Infectious Diseases
Nancy, France. Her main research interest lies in Specialist. Debra Goff is an Infectious Diseases Specialist
antimicrobial stewardship and vaccination practices with the and founding member of the Antimicrobial Stewardship Program
aim of preventing the emergence of bacterial resistance to at The Ohio State University Wexner Medical Center (OSUWMC)
antibiotics. in Columbus Ohio. She is the past-Director of the Infectious
Diseases Residency program at OSUWMC. She is an Associate
Professor Pulcini is Secretary of ESGAP, the European Society
Professor at the College of Pharmacy working with the One
for Clinical Microbiology and Infectious Diseases (ESCMID)
Health Antibiotic Stewardship team at OSU. Dr. Goff received
Study Group for Antimicrobial stewardship; she was editor for an
her Bachelor of Pharmacy and Doctor of Pharmacy degrees from
ESGAP book on Antimicrobial stewardship.
the University of Illinois at Chicago, where she also completed
She is or has recently served also as Expert for the National her residency.
Antibiotic Plan of the French Ministry of Health, the ECDC and
Dr. Goff is a 2016 TEDx Columbus speaker on antibiotics “just
the WHO. As well as serving as an Associate Editor for the
in case” there’s infection. She is the international advisor to
journal Clinical Microbiology and Infection, Professor Pulcini has
the Federation of Infectious Diseases Society of South Africa
also authored or co-authored over 160 international publications.
(FIDSSA) mentoring South African pharmacists. She received the
She received in 2017 the ESCMID Young Investigator Award.
2016 OSU Emerging International Outreach and Engagement
Award for her work in South Africa. She is the 2017 American
College of Clinical Pharmacy (ACCP) recipient of the Global
Health Award. She serves as a faculty mentor to young African
leaders as part of the Mandela Washington Fellowship Program.
Dr. Goff is part of the World Health Organization (WHO)
Pathogens Priority List Working Group. She serves on the
IDWeek planning committee for the Infectious Disease Society
of America (IDSA) and Making a Difference Infectious Diseases
(MAD-ID) annual meeting.
Her interests include antimicrobial resistance, the application
of rapid diagnostic tests with stewardship interventions, use of
Twitter to increase global engagement and cross collaboration
with surgeons, oncologists, veterinarians, and patient advocate
organizations in antibiotic stewardship. She lectures nationally
and internationally as an antimicrobial stewardship advocate and
tweets regularly on topics relevant to antibiotic stewardship.

KHALID KIRSTY
ELJAALY BUISING
Khalid Eljaaly, PharmD, CAPPS, MS, BCPS, is an assistant Associate Professor Kirsty Buising is an infectious
professor and infectious disease/antibiotic stewardship diseases physician working for the Victoria Infectious
pharmacist in faculty of pharmacy, King Abdulaziz University, Diseases Service (VIDS) at the Royal Melbourne Hospital in
Jeddah, Saudi Arabia, and an associate faculty/research fellow Melbourne, Australia. She is deputy director of the National
in the University of Arizona, Tucson, AZ, USA. He graduated with Centre for Antimicrobial Stewardship and chief investigator
a PharmD degree from King Abdulaziz University. He completed for the Australian National Health and Medical Research
his PGY1 pharmacy practice residency at a Tuft-University Council (NHMRC)-funded Centre for Research Excellence in
affiliated hospital and his PGY2 infectious disease pharmacy Antimicrobial Stewardship. Kirsty also holds an appointment
residency at BIDMC, a Harvard Medical School-affiliated hospital as a clinical research physician at VIDS, leading research and
in Boston, MA, USA. Then, he completed both infectious development for the Guidance Group. Kirsty serves on advisory
disease/antibiotic stewardship pharmacy fellowship and Master groups at state, national and international levels in the areas
of Science in clinical translational sciences at University of of antimicrobial stewardship, guideline development and
Arizona. He is a member of the social media committees of healthcare associated infection.
both the Society of Infectious Diseases Pharmacists (SIDP) and
Kirsty completed her doctorate of medicine on the use of
the Infectious Diseases Practice and Research Network of the
computerised decision support for antimicrobial stewardship,
American College of Clinical Pharmacy. He is also a member of
and a Masters of Public Health. Her team have successfully
the antibiotic stewardship committee of SIDP, a member of the
received NHMRC Partnership grants and a Centre for Research
editorial advisory board of Contagion®, a member of the Saudi
Excellence to develop their work in antimicrobial stewardship.
Ministry of Health stewardship implementation team. His Twitter
She has served as part of the authorship group for Therapeutic
account is called “Antibiotic Tweets” and his handle is
Guidelines: Antibiotic, working on national prescribing
@khalideljaaly.
guidelines. As an advisor to the Australian Commission
for Safety and Quality in Healthcare, she has had a role in
influencing policy. The National Centre for Antimicrobial
Stewardship team have conducted national surveys to gather
data on antibiotic use in Australia. The Guidance team have
developed electronic tools for antimicrobial stewardship that
have been implemented in over 60 Australian hospitals and
run national workshops to build capacity amongst doctors,
nurses and pharmacists to improve the way we use antibiotics
to optimise patient outcomes, and help to tackle antibiotic
resistance. Kirsty has taught at international workshops and
advised on regional initiatives to improve antimicrobial use.

MUSHIRA ADRIAN
ENANI BRINK
Dr. Mushira Enani, MbChB, FRCPE, FACP, FIDSA Clinical Microbiologist, Ampath National Laboratory
Medical Director & Infectious Diseases Consultant, Services, Milpark hospital, Johannesburg, South Africa
department of Medicine. Assistant Dean of Female Affairs, and Associate Professor, Division of Infectious Diseases and
Assistant Professor of Medicine, King Fahad Medical City, Riyadh HIV Medicine, Department of Medicine, Groote Schuur Hospital,
Saudi Arabia University of Cape Town, Cape Town, South Africa.
Dr. Enani is a graduate of King Abdulaziz University (KAU), Dr Adrian Brink gained his MB BCh degree from the University
faculty of medicine, Jeddah, Saudi Arabia. She joined Internal of Pretoria in South Africa in 1984, before completing further
Medicine residency training program in Riyadh, King Khalid medical training including his M Med (Clinical Microbiology)
university hospital/ King Saud university where she obtained degree, in 1994. He currently works in Johannesburg, South
the regional Arab Board in Internal Medicine & was selected as Africa, as Head of Clinical Microbiology at the Ampath National
the best resident in performance as R2. She is a member of the Laboratory Services, Milpark hospital, Johannesburg.
Royal College of Physicians of Edinburgh (MRCPE).
Dr Brink was founding President of the Federation of Infectious
Currently, Dr. Enani works at King Fahad Medical City (KFMC) Diseases Societies of Southern Africa and is an Executive
in Riyadh as ID consultant in the department of Medicine, Member of the latter council. He is currently co-chair of the
is Assistant Professor of Medicine, King Saud Bin Abdulaziz South African Antibiotic Stewardship Program (SAASP). He has
University for Health Sciences and Assistant Dean for female presented at national and international congresses and has
Affairs in Faculty of Medicine at KFMC and Medical Director of authored or co-authored more than 70 papers in peer-reviewed
Main Hospital. journals, including Lancet Infectious Diseases, the International
Journal of Antimicrobial Agents, Emerging Infectious
Diseases and the Journal of Antimicrobial Chemotherapy.
He is also serves on the editorial boards of several Journals
incl. Infectious Diseases in Clinical Practice, Frontiers in
Microbiology and the Southern African Journal of Infectious
Diseases. Dr Brink is senior author of the Massive Open Online
Course on Antimicrobial Stewardship and interactive e-Book
of Antimicrobial Stewardship (British Society of Antimicrobial
Chemotherapy and University of Dundee, Scotland). He currently
serves on the South African Minister of Health’s Ministerial
Advisory Committee (MAC) on antimicrobial Resistance
Dr Brink’s research interests include antibiotic resistance in
community-acquired and intensive-care-related infections, the
pharmacokinetics and outcome measures of antibiotics in ICU
patents including antimicrobial stewardship (AMS) in primary
care and in hospitals. In addition, the use of quality improvement
models and behaviour change techniques in AMS.

ANAHÍ REENA
DRESER RAVEENDRAN
Anahí Dreser is a researcher and lecturer in the Centre Consultant, Dept of Clinical Microbiology & Immunology,
for Health Systems Research at the Mexican National Sir Ganga Ram hospital.
Institute of Public Health (INSP). She is the co-leader of the
Dr. Reena Raveendran has acquired her MBBS from Govt.
research group Medicines in Public Health: Access, use,
Medical College, Kottayam, Kerala in 1998. She then pursued
and antimicrobial resistance. Her research interests include
her MD in Clinical Microbiology from Govt. Medical College,
pharmaceutical policies, antibiotic stewardship programmes,
Thiruvananthapuram, Kerala in 2003.
medicines consumption, and quality of health care.
She joined Sir Ganga Ram hospital in 2004, as Senior Research
Anahí Dreser is a medical doctor, holds a MSc in Control of
Officer, WHO project. She was the key person in the successful
Infectious Diseases, and is a PhD candidate in Public Health
completion of the project “Community-based Surveillance of
and Policy (LSHTM, UK). Her doctoral investigation analyses the
antimicrobial Use and Resistance in Resource Constrained
process of developing antibiotic policies in Mexico. Currently,
Settings”.
she collaborates with key stakeholders in Mexico as well as with
the Pan-American Health Organization in initiatives directed at Then onwards she has been working as a consultant with
improving the use of antibiotics and containing antimicrobial Sir Ganga Ram hospital in various sections and is currently
resistance. looking after Tuberculosis diagnosis. Areas of her special
interests include bacteriology, mycobacteriology, antimicrobial
stewardship, quality control and controlling spread of
tuberculosis. She has more than 25 publications in reputed
national and international journals. She has presented many
papers & posters and delivered lectures in various national and
regional conferences. She is an integral part of the organization
team conducting various National conferences and workshops
by Sir Ganga Ram Hospital.
She is an active member of various professional bodies like
Indian Association of Medical Microbiologists, Delhi Chapter
- Indian Association of Medical Microbiologists, Hospital
Infection Control Society and Clinical Infectious Diseases
Society. She is also a certified internal auditor by ISO 15189 and
NABL 112 as well as NABH. She takes keen interest in various
quality control activities of the Dept. of Microbiology as well as
the hospital at large.

AUTHOR: CHAPTER 16
CHAND
WATTAL
Prof. (Dr.) Chand Wattal is presently working as Hony. Board of Ind J of Paed., J of Lab. Physicians, IJMM AND IJMR In
Senior Consultant & Chairman Dept. of Clinical recognition of his academic achievements; he has been assigned
Microbiology , Ganga Ram Institute for P G Education & the task of Chief Investigator WHO (Geneva) Project on Rational
Research , Sir Ganga Ram Hospital, Rajinder Nagar, New Antibiotic Usage which has finished its Phase I & II. Phase III
Delhi,. India. He did his MD (Medical Microbiology) from PGI, has been funded by Melinda Bilgates Foundation currently. The
Chandigarh, in Jan 1983; MBBS from GMC, Kashmir 1977 & has findings have got chronicled in the WHO publications, 2010-
a total professional experience of more than 30 years. Dr. Wattal 11 He has participated as guest lecturer and made scientific
has been a postgraduate teacher and a guide/co-guide of MD presentations in 169 National and International Conferences.
since 1985 and for DNB Microbiology since 2003. He is an Dr. Wattal has been the recipient of several awards and brought
astute academician. He is an expert to the technical advisory laurels to his institution through such awards. He has been
committee, Ministry of Health and Family Welfare, Government awarded by the Lt. Governor of Delhi the “Dharma Vira Award
of India & is on several Task Forces for Rational Antibiotic Use for excellence” in his profession for the year 2004; this award is
(DGHS) and its Researchable Areas with ICMR. The Department given every year to the best consultant of the hospital and one
of Clinical Microbiology, Sir Ganga Ram Hospital (SGRH) which of his publications was awarded S. Nundy Award as the best
Dr. Wattal is heading; brings out SGRH Microbiology Newsletter publication of the year 2009. Awarded long distinguished service
twice every year giving the details of the antibiogrammes and award by Shri J.P.Nadda, Union Health Minister in 2015.Was
other articles of academic interest to the clinicians and clinical awarded the best publication of the year in Virology published
microbiologists ever, since 1995 which is also webcast. Dr. in IJMM by the Association of The Medical Microbiologists of the
Wattal has 90 research & 15 book publications in peer-reviewed country in the year 2012. He has been a valued office bearer of
journals to his credit out of which, 36 are in International IAMM-DC since 2006. Was re-elected twice as its treasurer and
journals; has delivered 220 guest lectures and chaired 94 is currently the ex-officio secretary of this society. He has been
scientific sessions, which includes publications in Medical Clinics elected unopposed to the executive council of the National Body
of North America, Lancet Infectious Diseases to name a few, of IAMM. He has also been entrusted with the job of running
has made contribution in Book Series/Lung Biology in Health an EQAS program for North and North East of India for the
and Disease on a topic “Pulmonary Hydatid Diseases in India, specialty of Clinical Microbiology under the aegis of the National
Diagnosis and Management” Publisher: Marcel Decker. Inc.,USA. Body of IAMM of the country since Jan 2014.His pioneering
His books on “ Emergencies in Infectious Diseases: from Head contribution to the country and the specialty of Clinical
to Toe” was released in April 2009 by Vice Chancellor, Jamia Microbiology has been immense in the field of monitoring of
University, Delhi.; Post Transplant Infections was released by Prof antibiotic resistance and development of antibiotic policy in the
K.S. Chugh on 13 Dec 2013 and Hospital Infection Prevention: country in the capacity of a member of the National Task Force
Principles & Practices (Springer Publication) was released on 20 for framing antibiotic policy. In recognition of his outstanding
Jan 2014 . He was twice Guest Editor: Journal of International contribution in the field of medicine and service to the mankind
Medical Sciences Academy (JIMSA) Special issue July-Sept. Delhi Medical Association conferred upon him “Vishisht Chikitsa
2004 on ‘Advances in Clinical Microbiology and Infections Rattan Award on Doctor’s Day 10th July 2016. He is a sought
Diseases practice in India” Jan-March 2010 on “Emerging after speaker for his specialty in the country and abroad.
infections: Indian Perspective.” . He is on the panel of Editorial

AOIFE ANDREW
FLEMING M. MORRIS
Dr Aoife Fleming is a Lecturer in Clinical Pharmacy at Dr. Morris obtained his MD (1994) degreefrom the
University College Cork , Ireland. She holds a joint University of Toronto. He trained in Internal Medicine from
appointment with the Pharmacy Department at the Mercy 1994 to 1997 at the University of Toronto, where he subsequently
University Hospital as a research Pharmacist since 2016. She completed sub-specialty training in Infectious Diseases in
graduated with a degree in Pharmacy from Trinity College 1999. He went on to complete a Master of Science degree
Dublin in 2004 and completed a Masters in Hospital Pharmacy in Epidemiology from the Harvard School of Public Health in
in 2007 while working at Beaumont Hospital Dublin. She has 2000, while completing a Bayer Healthcare-Canadian Infectious
extensive experience working the hospital and community Diseases Society (now AMMI Canada) research fellowship under
pharmacy settings. Dr Fleming completed a Health Research the supervision of ProfessorAllison McGeer.
Board Doctoral Scholarship in Health Services Research in
Dr. Morris spent 6 years with the Department of Medicine
2014 at the School of Pharmacy, University College Cork. Her
at McMaster University and Hamilton Health Sciences as a
PhD investigated Antimicrobial Stewardship in Ireland with a
consultant in infectiousdiseases and general internal medicine.
specific focus on long-term care facilities. Aoife has published
While there, he helpeddevelop an antimicrobial stewardship
and collaborated in the area of antimicrobial stewardship and
program in the Hamilton General Hospital intensive care unit.
continues to conduct research in this area.
(This program won the Canadian Healthcare Excellence in Quality
Award in 2006.) He returned to the University of Toronto in
2007, where he joined the Division of Infectious Diseases in the
Department of Medicine at Mount Sinai Hospital and University
Health Network. He is currently Professor, and works as a
consultant in Infectious Diseases and General Internal Medicine.
Dr. Morris is past Chair of the Specialty Committee of Infectious
Diseases with the Royal College of Physicians and Surgeons of
Canada, Chair of the Antimicrobial Stewardship and Resistance
Committee for the Association of Medical Microbiology and
Infectious Diseases Canada, and Chair-elect ofthe Antimicrobial
Stewardship Committee for the Society of Healthcare
Epidemiology of America.
He is the founding Director of the SinaiHealth System-University
Health Network Antimicrobial Stewardship Program(SHS-UHN
ASP), formed in 2009. The SHS-UHN ASP is the first and largest
antimicrobial stewardship program in Canada, overseeing
antimicrobials in 3 acute care hospitals, 1 cancer hospital, and 3
rehabilitation facilities, and a long-term care facility.He worked
with Accreditation Canada to makeCanada the first jurisdiction
in the world to require antimicrobial stewardship in hospitals.
Hehas authored or co-authored over 100 peer-reviewed
publications, with an emphasis on antimicrobial stewardship,
critical care, and Staphylococcus aureusbacteremia.

HAIFA SANJEEV
LYSTER SINGH
Haifa Lyster FFRPS, FRPharmS Dr Sanjeev Singh is a pediatrician by training and did
Consultant Pharmacist in Transplantation & Ventricular his MPhil in Hospital Management. He completed his PhD
Assist Devices (VADs) at The Royal Brompton & Harefield NHS in Infection Prevention and Control. He is a Chair of Infection
Foundation Trust. Prevention and Antibiotic Stewardship at Amrita Institute of
Medical Sciences at Kochi
Haifa graduated from the School of Pharmacy, University of Bath
in 1992 and continued her studies obtaining a Masters degree He worked as a Regional Coordinator at WHO-India in a Disease
at London School of Pharmacy and is a qualified independent eradication program before joining as Sr Medical Superintendent
non-medical prescriber. She is both a Fellow of the Royal at AIMS, Kochi.
Pharmaceutical Society and of its’ Faculty.
He has gained his fellowship on Healthcare worker Safety from
Haifa has worked in thoracic transplantation & VADs based at University of Virginia and fellowship on Health Technology
Harefield hospital since 1998 with a leading role in managing Assessment (HTA) from University of Adelaide. He is an
VAD and heart and lung transplant patients in all aspects of Improvement Advisor from Institute of Healthcare Improvement,
their pharmaceutical care, particularly in anti-infective and US.
immunosuppression regimens. She is currently undertaking a
Dr Sanjeev is also an Ambassador from India to Society of
PhD research doctorate developing PK/PD models of a number
Healthcare Epidemiology of America (SHEA) and has been
of antifungal agents in ECMO patients.
adjudged as “Heros of Infection Control” by Association
Haifa is the pharmacy lead for NHSE Cardiothoracic Clinical of Professionals of Infection Control (APIC), US. He is the
Reference Group and Vice chair of SOTPA (Solid Organ International surveyor at International Society for Quality (ISQua).
Transplant Pharmacy Association). She is also currently the Vice He is presently the Vice Chairman of Research Committee at
chair (elect) of the Pharmacy & Pharmacology council for the NABH, Chairman of Technical Committee at AHPI (Association
International Society of Heart & Lung Transplantation (ISHLT). of Healthcare Providers of India) and Health Sector Skills Council
of India (GOI), a member of Drug Safety Council (GOI) and
member of National Advisory Body on Occupational Exposures.
He is also a Principal Assessor for ISO9001:2015 and NABH.
He is an external consultant to WHO, a Technical Advisor to
several State government healthcare projects (E learning,
reduction of IMR, Antibiotic Stewardship and Infection Control),
Technical Expert for University of Antwerp’s Point Prevalence
Surveillance and Institute of Healthcare Improvement’s (US) on
Neonatal Collaborative program and a member of Core Working
and Technical Advisory Group on Antibiotic Stewardship for the
State of Kerala.

DAVID LAURA
ENOCH WHITNEY
David is a consultant microbiologist in Cambridge. He
trained in London and did medical jobs in London and
the South East before training in medical microbiology at the
Royal Free Hospital in London and then Cambridge. He was
a consultant initially in Peterborough before moving back to
Cambridge 5 years ago.

SANJAY PRIYA
PATEL NORI
Dr Sanjay Patel is a paediatric infectious diseases and Priya Nori, MD. Medical Director, Antimicrobial
immunology consultant working at Southampton Stewardship Program
Children’s Hospital, England. His main areas of interest are
Co-Director, OPAT Program
OPAT and antibiotic stewardship.
Assistant Professor of Clinical Medicine at the Albert Einstein
In 2012, he introduced the first paediatric outpatient parenteral
College of Medicine, Montefiore Health System
antibiotic therapy (p-OPAT) service in the UK. He chaired
the joint BSAC / British Paediatric Allergy, Immunology and
Infectious Diseases Group p-OPAT national working group
tasked to develop good practice guidelines for the introduction
and delivery of p-OPAT services in the UK, which were published
in October 2014.
He leads the antimicrobial stewardship service at Southampton
Children’s Hospital and was a member of the NICE antibiotic
stewardship guideline development group which published
guidelines in 2015. He is on the BSAC OPAT standing committee
and sits on BSAC council. He is co-lead for the module on
antimicrobial stewardship for the European Society of Paediatric
Infectious Diseases on-line antibiotic management course
and runs infectious diseases courses at Imperial College and
in Iceland. As project lead of Healthier Together Wessex, he
is working with primary care colleagues to improve antibiotic
prescribing in community based settings (www.what0-18.nhs.uk).

KARIN ENRIQUE
THURSKY CASTRO-SÁNCHEZ
Professor Karin Thursky is the Director of the National Enrique Castro-Sánchez is currently combining an Early
Centre for Antimicrobial Stewardship, the Deputy Head Career Research Fellowship exploring increased
of Infectious Diseases at the Peter MacCallum Cancer Centre, participation of nurses in antimicrobial stewardship decision-
and the Director of the Guidance Group at Royal Melbourne making and positions as Lead Research Nurse at the Health
Hospital. An infectious diseases physician, she is a leader in Protection Research Unit in AMR and HCAI at Imperial College
the design and implementation of antimicrobial stewardship London, working on the theme "Innovations in behaviour
programs, with a particular expertise in the use of computerised change, technology and patient safety to improve infection
systems to support better antibiotic prescribing. The Guidance prevention and antimicrobial use".
program, which supports clinical teams in hospitals to monitor
He was awarded a PhD cum laude in Nursing at the University
the appropriateness and safety of antibiotic use, is implemented
of Alicante (Spain) in 2015. He trained in nursing and
in over 60 hospitals across Australia. The National Antimicrobial
management of nursing services in Spain, followed by an MSc
Prescribing Survey is a core component of the National
in Public Health at the London School of Hygiene and Tropical
Antimicrobial Resistance Strategy. Her multidisciplinary team of
Medicine in 2003. His research interests include health literacy
clinician and health service researchers is working to establish
in infectious diseases and healthcare-associated infections;
and implement antimicrobial stewardship programs across animal
health inequalities on infectious diseases; policy influence on
and human health sectors.
management of infectious diseases.
Enrique has got a broad clinical experience in tropical and
infectious diseases including malaria, leprosy, tuberculosis, HIV
and sexually transmitted infections. He has consulted to the
WHO Global Infection Prevention and Control Unit in Geneva,
developing leadership materials to support the new Core
Components in Infection Prevention and Control. He sits at
BSAC Council, he is a Florence Nightingale Foundation Scholar,
member of the European Academy of Nursing Science, and was
elected as Emerging Leader in International Infectious Diseases
in 2016 by the International Society for Infectious Diseases”.

TIMOTHY MICHAEL
GAUTHIER CORLEY
Timothy P. Gauthier, Pharm.D., BCPS-AQ ID is a Michael joined the British Society for Antimicrobial
pharmacist with advanced training and experience in Chemotherapy as its Senior Policy and Public Affairs
the fields of infectious diseases and antimicrobial stewardship. Officer in May 2017.
He remains active in teaching, clinical practice, research, and
He has previously worked as the Director of Public Affairs
service. You can find him on social media @IDstewardship.
for Adoption UK, and as the Head of Communications and
Campaigns for the Royal Society for the Prevention of
Accidents (RoSPA).
Michael is a qualified Senior Journalist who has worked for both
the Coventry Telegraph and the Gloucestershire Echo, where he
was the Politics Editor.
He has a Bachelor of Arts degree in History and Politics, and a
Master of Arts degree in Modern Literature (which was awarded
with distinction).

EDITOR PRODUCTION AND DESIGN TEAM
GAVIN TRACEY
BARLOW GUISE
Gavin Barlow, MB ChB DTM&H MD FRCP, Consultant in Tracey Guise is Chief Executive Officer at the BSAC.
Infection, Hull & East Yorkshire Hospitals NHS Trust, Hon. She is a seasoned senior executive with over 20 years’
Senior Clinical Lecturer, Centre for Immunology and Infection, experience within not for profit organisations including past
Hull York Medical School and University of York. leadership roles at the Royal College of Paediatrics and Child
Health and an early career in the civil service. In her current role
GB qualified in Medicine at Leicester University in 1993 and
Tracey contributes to and supports delivery of the strategic aims
trained in infectious diseases and general internal medicine
of the Society and, most recently, its global education agenda.
in Leeds, Sheffield and Dundee, including a two-year research
training fellowship at the University of Dundee. GB’s main
clinical interests are orthopaedic infection, outpatient
parenteral antibiotic therapy (OPAT), antimicrobial stewardship,
and the management of complex bacterial and healthcare-
associated infections.
Research interests are broad, but predominantly focus on
the epidemiology and clinical care of infections commonly
managed in the NHS. GB was awarded Fellowship of the Royal
College of Physicians, London in 2009 and is the British Society
for Antimicrobial Chemotherapy (BSAC) Officer for Stewardship
and Surveillance.

PRODUCTION AND DESIGN TEAM
SALLY NEIL
BRADLEY WATSON
Sally has a background in the quality assurance of Neil is a Creative Graphic, UI designer and Web
medical education and project management of yearly Developer based in Cambridgeshire. Neil has worked with
awards to recognise excellence in teaching and innovative the British Society for Antimicrobial Chemotherapy to provide
teaching initiatives. web development and design services for the Society’s portfolio
of national and international activities and is an integral part of
Since joining BSAC she is part of the team coordinating,
the BSAC team. Neil has over a decade of experience of high
developing and creating eLearning courses for a global
level development projects and has collaborated with leading
audience, including a suite of massive open on-liine courses,
software companies including and PlayStation, XBOX, Nintendo,
Webinar based courses for General Practitioners on behalf of
BBFC & UKIE, as well as other charitable bodies including
Public Health England and this eBook.
Wembley National Stadium Trust and Animal Health Trust &
Wood Green Animal Charity.

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E-BOOK

How do antibiotics work? ...................................................... 14 Long term care ....................................................................... 34

Where does resistance occur and how Misuse of antibiotics .............................................................. 35

What are the drivers for the use and

Stewardship as a solution to Combat AMR ...................... 23 Key principles of prudent

Towards integrated models of ams .................................... 70

Antimicrobial stewardship committee ................................ 51 The use of currently available diagnostic

Conclusion ............................................................................... 64 Commonly used antimicrobial

Clinical application of PK/PD

Interactive Case study .......................................................... 86

Getting started with improving

Position of antimicrobial stewardship The role of behaviour and culture in

How to identify priority areas in Hierarchies ............................................................................ 130

Additional Interventions ..................................................... 102 CHAPTER 13 - KNOWLEDGE 133

What are competences for antimicrobial

Educational Resources ....................................................... 143 AMS “breakthrough series collaborative”

The importance of collaborative learning

CHAPTER 15 - 153 Story 2: Prescription auditing as a concept

Other contributory factors ......................................... 179

Story 2: The process and impact of introducing

Conclusions ................................................................. 183

STEWARDSHIP IN LONG Rationale ................................................................................ 214

Impact of Antimicrobial Resistance .................................. 188 Selection of antimicrobial agent

Antimicrobial stewardship ................................................. 190 Repeat dosing ........................................................................ 217

Sepsis in LTCF ....................................................................... 195 Topical adminstration of irrigations,

CHAPTER 18 - 197 Summary ................................................................................ 219

Funding of antifungals and its effects on AFS ............. 223

Summary ................................................................................ 212 Who do you need to involve? ............................................ 227

What do you need? ............................................................ 228

Antibiotic prescribing for children Expanding the participation of nurses

Evaluating the quality of antibiotic Public health and community nursing

Summary ................................................................................ 241 Integration between nursing roles

CHAPTER 23 - 242 Stewardship, a target for nurses

Conclusion ............................................................................ 250 Research ............................................................................... 280

Rapid Diagnostic Tests ...................................................... 280

Using information technology to CHAPTER 27 - 284

Politicians .............................................................................. 289

Chapter 2 .............................................................................. 295 Chapter 2 - Margaret Duguid ........................................... 325

Chapter 4 .............................................................................. 299 Chapter 4 - Conor Jamieson ............................................. 327

Chapter 5 .............................................................................. 300 Chapter 5 - Paul Pottinger ................................................. 327

Chapter 7 .............................................................................. 302 Chapter 7 - Nick Brown ..................................................... 329

Chapter 8 .............................................................................. 303 Chapter 8 - Alasdair MacGowan

Chapter 15 .............................................................................. 311 Chapter 13 - Diane Ashiru-Oredope ................................ 333

Chapter 16 ............................................................................. 312 Chapter 14 - Marc Mendelson ........................................... 334

Chapter 17 ............................................................................... 313 Chapter 15 - Debbie Goff, Celine Pulcini,

Chapter 19 ............................................................................. 315 Chapter 16 - South Africa: Adrian Brink,

Chapter 24 - Karin Thursky ................................................ 344

Chapter 25 - Enrique Castro Sanchez ............................. 344

Chapter 26 - Debra A Goff ................................................. 335

Chapter 27 - Michael Corley ............................................. 345

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This educational resource is complimented by the availability of

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DILIP NATHWANI OBE