WHO methodology for a global

programme on surveillance of
antimicrobial consumption
Version 1.0
Table of Contents
1. Background ..................................................................................................................................... 5
2. The WHO program on surveillance of antimicrobial consumption ................................................ 6
2.1. Aim and objectives .................................................................................................................. 6
2.1.1 Aim .................................................................................................................................. 6
2.1.2 Objectives........................................................................................................................ 6
2.2. Activities at three levels .......................................................................................................... 6
2.2.1. National level .................................................................................................................. 6
2.2.2. Regional level .................................................................................................................. 7
2.2.3. Global level...................................................................................................................... 7
2.3. Setting up a national surveillance program on antimicrobial consumption........................... 8
3. Methodology................................................................................................................................... 9
3.1. Definitions ............................................................................................................................... 9
3.2. Measurement issues ............................................................................................................... 9
3.3. ATC Classification system ........................................................................................................ 9
3.3.1. Unit of measurement Defined Daily Dose (DDD).......................................................... 10
3.4. Antimicrobials included in monitoring.................................................................................. 11
3.5. Healthcare sectors to be monitored ..................................................................................... 12
3.5.1. The community sector .................................................................................................. 12
3.5.2. The hospital sector ........................................................................................................ 12
3.5.3. Public and private sectors ............................................................................................. 12
4. Data collection for antimicrobial consumption ............................................................................ 13
4.1. Elements of data collection .................................................................................................. 13
4.1.1. Antimicrobial consumption data .................................................................................. 13
4.2. Data sources for consumption estimates ............................................................................. 14
4.2.1. Flow of antimicrobials ................................................................................................... 14
4.2.2. Potential sources of information on antimicrobial consumption ................................. 15
4.3. Denominator data ................................................................................................................. 18
4.4. Reporting metrics.................................................................................................................. 18
4.5. Contextual information relating to data collection .............................................................. 18
5. Data management ........................................................................................................................ 19
5.1. Data flow ............................................................................................................................... 19
5.2. Data collection ...................................................................................................................... 19
5.3. Data submission .................................................................................................................... 20
 5.4. Data analysis ......................................................................................................................... 20
5.5. Dissemination of data ........................................................................................................... 20
6. Template for Data Collection ........................................................................................................ 21
6.1. Structure of template ........................................................................................................... 21
6.2. Variables................................................................................................................................ 22
6.2.1. Variables for antimicrobial medicines register ............................................................. 22
6.2.2. Variables for consumption estimates (packages and DDDs) ........................................ 23
6.2.3. Variables for population estimates ............................................................................... 23
6.2.4. Variables for population-adjusted estimates................................................................ 23
6.3. Contextual information ......................................................................................................... 23
7. Glossary ......................................................................................................................................... 24
8. Annexes ......................................................................................................................................... 27
Annex 1: Introduction to ATC and DDD methodology ..................................................................... 28
Annex 2: List of ATC sub-groups under surveillance......................................................................... 36
Annex 3: Variables of the register and consumption datasets ......................................................... 38
Annex 4: Conversion factor List ........................................................................................................ 44
Annex 5: Administration Route List .................................................................................................. 44
Annex 6: Measurement Unit List ...................................................................................................... 44
Abbreviations
AMC Antimicrobial consumption

ATC Anatomical Therapeutic Chemical

CC Collaborating Centre

DDD Defined Daily Dose

DID Defined Daily Doses/1000 inhabitants/day

EphMRA European Pharmaceutical Market Research Association

GAP Global Action Plan

INN International Nonproprietary Name

OIE World Organisation for Animal Health

OTC Over-the-counter

PBIRG Pharmaceutical Business Intelligence and Research Group

PDD Prescribed Daily Dose

PIY Packages/1000 inhabitants/year

WHA World Health Assembly

WHO World Health Organization

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1. Background
At the Sixty-eighth World Health Assembly (WHA) held in May 2015, Member States
adopted the Global Action Plan on antimicrobial resistance and the WHA urged Member
States to implement the action plan recognizing this may need to be adapted to specific
contexts and national priorities.

The Global Action Plan (GAP) has five objectives:

1. Improve awareness and understanding of antimicrobial resistance;

2. Strengthen surveillance and research;
3. Reduce the incidence of infection;
4. Optimize the use of antimicrobial medicines; and
5. Ensure sustainable investment in countering antimicrobial resistance.

Specifically related to objective 4, Member States are requested to provide “stewardship

programmes that monitor and promote optimization of antimicrobial use at national and
local levels in accordance with international standards in order to ensure the correct choice
of medicine at the right dose on the basis of evidence”. Thus, an important element of the
GAP is monitoring the consumption of antimicrobials. All countries have some data related
to the import, procurement, distribution or clinical use of antimicrobials in their
communities that can be used as the basis of stewardship and monitoring programs.

Data on the consumption of antimicrobials have a number of uses, including:

 To relate exposure to antimicrobials to the development of antimicrobial resistance;

 To identify and provide early warning of problems relating to changes in exposure
and utilization and to develop interventions to address problems identified;
 Monitoring the outcomes of interventions aimed at changing exposure;
 Assessing quality of prescribing against practice guidelines;
 Raising awareness in health professionals, consumers and policy makers about the
issues of antimicrobial resistance and the contribution of inappropriate use of
antimicrobials in humans.

Data on antibiotic use are collected and analysed in many high- and middle-income
countries and the World Organisation for Animal Health (OIE) is developing a database on
antibiotic use in animals. However, data are lacking on antibiotic use in human beings at the
point of care and from lower-income countries. The WHO program on surveillance on
antimicrobial consumption (AMC) is a global surveillance program for the collection and
reporting of data on antimicrobial consumption in humans at country, regional and global
level.
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2. The WHO program on surveillance of antimicrobial consumption

2.1. Aim and objectives

2.1.1 Aim

The aim of the protocol presented here is to provide a common methodology for the
measurement of the consumption of antimicrobial agents. This will allow monitoring of
trends over time at the national level, facilitate some comparisons between countries and
provide a common metric for reporting antimicrobial use at a global level.

2.1.2 Objectives

The primary objectives of the WHO program of surveillance of antimicrobial consumption

are:

 to provide a common methodology to the countries for collecting and reporting

national antimicrobial consumption data;
 to provide reliable and comparable national consumption data over time and
between countries;
 to provide information on the level of use and types of antimicrobials for policy-
makers and prescribers;
 to provide a methodology that can be integrated into a global WHO surveillance
program.

The secondary objectives of the WHO program are:

 to provide, as part of a national package, a methodology that can be integrated

in national program on surveillance of antimicrobial use and more generally in a
national program on antimicrobial resistance;
 to provide comparable consumption data with animal and agricultural
consumption data.

2.2. Activities at three levels

The WHO program on surveillance of antimicrobial consumption involves activities at three

levels – national, regional and global levels.

2.2.1. National level

Member States participating in the WHO program on surveillance of antimicrobial

consumption should set up a national team in charge of the surveillance of antimicrobial
consumption in the country. The AMC national team is responsible for establishing and
running the national surveillance program on antimicrobial consumption by collecting and
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validating the consumption data, by reporting the consumption data at the regional and
global level,and finally by publishing a report on the consumption of antimicrobials in the
country. In order to have support from the national authorities, the AMC national team
should be placed under the authority of the Ministry of Health.

To promote good integration of the surveillance of antimicrobial consumption with other

national activities related to antimicrobial use and resistance, the AMC national team should
have links with the national antimicrobial committee, and the program in charge of the
surveillance of antimicrobial resistance. In addition, as part of the “One Health” approach,
the AMC national team should have links with the programs in charge of the surveillance of
antimicrobial use and resistance in the animal and agricultural sectors.

It is recommended that the AMC national team is a multi-disciplinary team with at least
some members with pharmaceutical and data management skills. In some settings it may be
appropriate to establish a Technical Working Group to coordinate the data collection.
Where there are multiple data providers, including from the private sector, it may be
necessary to put contracts in place in order to facilitate data release.

2.2.2. Regional level

WHO Regional offices should set up an antimicrobial consumption team (AMC regional
team). The AMC regional team is responsible for supporting countries to implement a
national surveillance program on antimicrobial consumption and coordinating the WHO
surveillance program at regional level. As part of their tasks, the AMC regional team should
collate national antimicrobial consumption data from the countries, validate and analyse
these data, communicate with the countries on the data validation and finally publish a
regional report on antimicrobial consumption.

2.2.3. Global level

At global level, WHO should set up a global team for antimicrobial consumption (AMC global
team). This team is responsible for supporting regional offices and countries for the
surveillance of antimicrobial consumption and for coordinating the global surveillance
program on antimicrobial consumption. The AMC global team will collate data from the
regional offices and make these data available to the public in agreement with national
authorities.

Antimicrobial consumption is only one element of a national program on antimicrobial use.

Activities such as the development of clinical guidelines and protocols, the availability and
affordability of antimicrobial agents, restrictions on use of agents for particular clinical
conditions or to nominated prescribers and other activities related to the responsible use of
antimicrobials are beyond the scope of this document.
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2.3. Setting up a national surveillance program on antimicrobial

consumption

There are a number of steps in setting up a national program on surveillance of

antimicrobial consumption:

1. Establish the AMC national team with at least some members with skills on
pharmaceuticals and data management. A person of the AMC national team should
be nominated as WHO focal point for AMC and responsible for communication with
WHO.
2. Define the objectives of the surveillance program
3. Based on the defined objectives and available resources:
4. Identify the sources of data to be used in the surveillance program.
5. Communicate and organise meetings with the data providers to inform them on
purpose of the surveillance program and on the requested data. If needed organise
workshop with the data providers.
6. Start collecting the requested data from the data providers
7. Validate the data in cooperation with the data providers
8. Analyse the data
9. Report information on antimicrobial consumption to inform the national strategy
and publish the data at national level
10. Report the data to WHO
11. Provide feedback of the data collection and validation process to the data providers
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3. Methodology

3.1. Definitions

For the purpose of the protocol presented:

 Consumption data refer to estimates derived from aggregated data sources

such as import or wholesaler data, or aggregated health insurance data where
there is no information available on the patients who are receiving the
medicines or why the antimicrobials are being used. These data sources provide
a proxy estimate of use of antimicrobials.

Consumption data may be presented as total consumption for a country or may

be disaggregated by setting (community or hospital; public or private sectors).

 Antimicrobial use data refer to estimates derived from patient-level data. These
data may allow disaggregation of data based on patient characteristics (gender,
age), or indication for which the medicine is being used. Depending on the
source of information, it may be possible to determine the patients’ symptoms,
physician diagnoses and medications ordered. This will facilitate assessment of
clinical practice against agreed protocols and treatment guidelines.

Measuring consumption data is an important starting point for countries with limited
experience in data collection. With experience and as more sophisticated data sources
become available (e.g. e-prescribing records), it is expected that there will be more
emphasis on measuring antimicrobial use.

3.2. Measurement issues

There is a need for a common system of classification and standard metrics to facilitate
comparisons of antimicrobial consumption between health facilities, between countries and
between regions. The most commonly used classification system is the Anatomical
Therapeutic Chemical (ATC) classification system. The most commonly used measurement
metric is the number of Defined Daily Doses (DDDs). These are discussed in more detail in
the following section and in Annex 1.

3.3. ATC Classification system

The Anatomical Therapeutic Chemical (ATC) classification system is the most commonly
used method for aggregation of medicines data and allows flexibility in reporting by
medicine or groups of medicines. In this system, the active substances are divided into
different groups according to the organ or system on which they act and their therapeutic,
pharmacological and chemical properties.
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Medicines are classified in groups at five different levels.

Level 1: indicates the anatomical main group and consists of one letter.
There are 14 main groups. The group most relevant to work on
antimicrobials is group J Anti-infectives for systemic use. However, there
are some examples of antimicrobials classified in other main groups, e.g.
antibiotics used as intestinal anti-infectives are in ATC main group A
Alimentary tract and metabolism, while some oral and rectal anti-
protozoal agents are in ATC main group P Anti-parasitic products,
insectides and repellants.

Level 2: pharmacological/therapeutic subgroups, e.g. J01 is Antibacterials for

systemic use, J02 Antimycotics and J04 Antimycobacterials.

Level 3: chemical/pharmacological subgroups, e.g. J01C is Beta-lactam

antibacterials, penicillins

Level 4: pharmacological subgroup, e.g. J01CA is Penicillins with extended

spectrum

Level 5: chemical substance, e.g. J01CA01 is ampicillin and J01CA04 is amoxicillin.

More information on the ATC system is provided in Annex 1 and the full list of assigned ATC
codes is available at http://www.whocc.no/atc_ddd_index/.

3.3.1. Unit of measurement Defined Daily Dose (DDD)

The most commonly used measurement statistic is the number of Defined Daily Doses
(DDDs). The Defined Daily Dose (DDD) is the assumed average maintenance dose per day for
a medicine used for its main indication in adults. A DDD is only assigned for drugs that
already have an ATC code. The DDD, however, is only a technical unit of use and does not
necessarily reflect the recommended or average prescribed dose.

The DDDs for the anti-infectives are as a main rule based on the use in infections of
moderate severity. However, some anti-infectives are only used in severe infections and
their DDDs are assigned accordingly.

There are no separate DDDs for children which makes the DDD estimates for paediatric
formulations more difficult to interpret.

The numbers of DDDs is calculated as follows:

𝑻𝒐𝒕𝒂𝒍 𝒈𝒓𝒂𝒎𝒔 𝒖𝒔𝒆𝒅
Number of DDDs = 𝑫𝑫𝑫 𝒗𝒂𝒍𝒖𝒆 𝒊𝒏 𝒈𝒓𝒂𝒎𝒔
 11

Where the total grams of the medicine used is determined by summing the amounts
of active ingredient across the various formulations (different strengths of tablets or
capsules, syrup formulations, injections etc.) and pack sizes.

The numbers of DDDs provides a measure of extent of use, however for comparative
purposes these data are usually adjusted for population size or population group, depending
on the medicines of interest and the level of data disaggregation that is possible.

For most antimicrobials, the DDDs/1000 inhabitants/day (DID) will be calculated for the
total population including all age and gender groups.

It may also be possible to stratify the national estimates by age group, gender, sectors
(community and hospital, public and private). Where there is stratification there needs to be
careful consideration of the appropriate estimate for the denominator, e.g. DDDs/1000
children under 5 years/day or DDDs/1000 women/day.

3.4. Antimicrobials included in monitoring

The WHO surveillance program focuses only on antimicrobials for systemic use. Topical
antimicrobials are excluded.

WHO has defined a core set of antimicrobials that all countries should include in their
surveillance program:
Antibacterials J01
Antibiotics for alimentary tract A07AA
Nitroimidazole derivatives for protozoal diseases P01AB

In addition, the WHO surveillance program includes an optional list of antimicrobials that
countries may include in their surveillance program according to local needs and resources:
Antifungals J02
Antimycotics D01BA
Antivirals J05
Antimycobacterials for treatment of tuberculosis J04A
Antimalarials P01B

Finally, countries may include extra antimicrobial agents that are not in the core oroptional
lists in their national surveillance program. In this case, countries should collect and report
the results of these additional analyses separately at national level.

Countries should liaise with their Regional AMC team regarding reporting of any additional
analyses at regional level. For example, there may be interest in reporting consumption of
tuberculosis medicines in regions where there are several countries with large populations
of patients requiring treatment.
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A list of medicines and ATC codes is provided in Annex 2 and also as a worksheet in the Excel
Template for reporting (worksheet tab ATC).

3.5. Healthcare sectors to be monitored

Different types of healthcare sectors may be considered in monitoring of antimicrobial

consumption including:

 community and hospital sectors

 public and private sectors.

In many countries that are starting data collection, it will not be possible to disaggregate
data by sector and only total consumption data will be able to be reported.

3.5.1. The community sector

The community sector corresponds to primary care and may also include out-patient
hospital care; it is sometimes referred to as ambulatory care. Primary care corresponds to
care provided by general practitioners, family doctors, nurses, physician assistants,
pharmacists or clinical officers.

Residential care (e.g. nursing homes, day care centres) is also typically considered to belong
to the community sector.

As an example, in many countries, antimicrobials reported in the community sector are

usually prescribed by general practitioners and dispensed or supplied to the patients in
pharmacies or licensed drug stores.

3.5.2. The hospital sector

The hospital sector corresponds to care provided to in-patients (admitted patients) in

healthcare facilities. These can include general and district hospitals as well as secondary
and tertiary care hospitals and other specialist health clinics.

As an example, in many countries, antimicrobials reported in the hospital sector are usually
prescribed by hospital doctors and administered to the patients directly by the healthcare
professionals in those facilities.

3.5.3. Public and private sectors

Countries may also be able to collect antimicrobial consumption separately for public and
private sectors. This can provide important information about differences in prescribing
practices in the two sectors. However, national committees should report both sectors
combined to the WHO global reporting system.
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4. Data collection for antimicrobial consumption

Antimicrobial consumption is defined as quantities of antimicrobials used in a specific
setting (total, community, hospital) during a specific period of time (e.g. days, months, and
year). For global reporting, national estimates of consumption are reported for the calendar
year (January to December). The ATC/DDD methodology is used to standardise the data
collection and reporting of antimicrobial consumption.

4.1. Elements of data collection

There are three elements to the data collection, namely antimicrobial consumption data,
denominator data and descriptive or contextual information that is relevant for interpreting
the consumption estimates calculated (see Figure 1).

•Product level data

Antimicrobial •Consumed packages at product level (aggregated
consumption data packages)
•May be stratified by healthcare sectors

•Population under surveillance to which data apply

Denominator data •May be stratified by healthcare sectors

•Data source information, e.g. national reference data

Contextual information (total) or health care sector (community, hospital)
related to antimicrobial •Which antimicrobials are included in surveillance
consumption •Specific exclusions, e.g. nursing homes, day care
centres, psychiatric facilities, private sector

Figure 1 Elements of data collection

4.1.1. Antimicrobial consumption data

4.1.1.1. Product level data

The first step requires identification of all the products for the antimicrobial agents
registered (i.e., with marketing authorization) in the country – a valid national exhaustive
register of products. In some cases this will not already exist and this list of products will
need to be developed. For each antimicrobial substance, this means a list of all products by
formulation, strength and pack size. For commonly used products with multiple
manufacturers this could mean 50 or more product lines for a single INN like amoxicillin or
 14

ceftriaxone. The register file will need to be updated each year as new products receive
marketing authorization.

4.1.1.2. Package level data

Consumption is expressed as the total numbers of packages for each product in the register
of antimicrobial products that are consumed during the defined period of time. Mostly
these will be annual (yearly) data. However data may be available for different time periods
such as quarterly.

4.1.1.3. Substance level data

Consumption at substance level can be summarized as aggregated DDDs. As noted earlier,

the numbers of DDDs is calculated as follows:
𝑻𝒐𝒕𝒂𝒍 𝒈𝒓𝒂𝒎𝒔 𝒖𝒔𝒆𝒅
Number of DDDs = 𝑫𝑫𝑫 𝒗𝒂𝒍𝒖𝒆 𝒊𝒏 𝒈𝒓𝒂𝒎𝒔

Where the total grams of the medicine used is determined by summing the amounts
of active ingredient across the various formulations (different strengths of tablets or
capsules, syrup formulations) and pack sizes. The DDD value is assigned by the WHO
Collaborating Centre (http://www.whocc.no/atc_ddd_index/).

4.2. Data sources for consumption estimates

4.2.1. Flow of antimicrobials

Procurement and supply of antimicrobial agents at the country level may be complex. In its
simplest and ‘idealised’ form, for a country without domestic manufacturing capacity,
antimicrobials are imported (licensed imports with customs records), are supplied and
distributed by licenced wholesalers and distributors to public and private hospitals,
community health facilities and community pharmacies and then provided to patients based
on prescriptions written by appropriately registered health care professionals. In some
countries, these medicines will be reimbursed by health insurance programs, with or
without the imposition of patient co-payments.

The reality in many countries is quite different. Antimicrobials may be sourced from both
international and domestic producers. Imports may be subject to re-export to other
countries; domestic producers may export part of their production. Orders may be placed
with wholesalers or directly with manufacturers. Imported products may be used in the
veterinary and agriculture sectors as well as for human use. Healthcare professionals and
patients may be able to import products directly. Antimicrobials may be purchased over-
the-counter as well as with prescription. Borders may be ‘porous’ with illegal imports and
exports. Patients may buy products in neighbouring countries where products are cheaper.
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4.2.2. Potential sources of information on antimicrobial consumption

There are a number of potential sources of information on consumption of antimicrobials:

 import data (using data from customs records and declaration forms)
 production records of domestic manufacturers (exclude any exports of products)
 wholesaler/distributor data – this could be data on procurement by wholesalers
or records of sales by the wholesalers to healthcare facilities and pharmacies
 public sector procurement records – these exist where there is both centralised
and decentralised purchasing of medicines for the public sector
 donations – this may relate to particular programs such as HIV, TB, malaria or for
special populations such as migrants and refugees
 records from community and hospital pharmacies and licensed drug stores
 data from health insurance programs
 prescribing records of doctors and dispensing records of pharmacists
 information on antimicrobial use from patients themselves.

These sources provide information with differing levels of detail on the consumption and
use of antimicrobials. It is important to understand the nature, scope and limitations of the
data collection from each of these sources; otherwise there is a risk of under- or over-
estimation of antimicrobial consumption. Table 1 summarises some of the strengths and
weaknesses of each of these data sources.

The sources differ in the degree of difficulty of gathering information. There may be a single
import authority in the public sector that retains records of all authorized importation, a
complex array of local and multi-national manufacturers, multiple wholesalers in the public
and private sectors, an insurance authority that covers only some and not all sectors of the
population, and private health care providers (hospitals, clinics, health care professionals)
that may be reluctant to provide information.

It will be up to governments in Member States to decide whether data collection is

voluntary or mandatory across all providers and all sectors. Changes in regulation or laws
might be necessary to oblige the data providers to deliver the requested information.

The data sources ‘close’ to the patient will provide the most reliable estimates of
antimicrobial consumption and will be more likely to provide data on age and gender of the
patient, provider details and indication for the antimicrobial prescription. However, these
will also be the most sophisticated and most expensive sources of data.

It is very important to correctly identify the data sources used in the country. If more than
one data source is used, it is important to be aware of overlaps in the information provided.
If they are treated as separate estimates and summed to provide ‘total consumption’ this
may overestimate actual antimicrobial consumption.
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Table 1: Strengths and limitations of data sources for antimicrobial consumption

Data source Strengths Limitations
Import data - Import permits issued by - Documentation may be
Government incomplete
- Centralized records - May include parallel trade stock
- Standardised reporting for movements
customs declaration forms including - Not account for smuggled goods or
product type (generic, branded), illegal entry of products
volume, port of origin, country of - Volumes match import cycles not
manufacture, batch number, expiry consumption patterns
date) - Are administrative records and not
- Includes OTC medicines formatted for research and analysis

Domestic - Local licensed producers should be - Private companies may be

manufacturers easily identified unwilling to provide data
- Can separate product volumes for - Volumes reflect production not
local use and for export consumption patterns
- Can request data in format
suitable for analysis

Public sector - Likely to have reasonable - Only provides data for public
procurement documentation of purchases sector
- Disaggregation of distribution data - May not reflect total public sector
to facility types (community and consumption if other procurement
hospital) and geographical location is undertaken by hospitals, health
is possible facilities
- May be single (or limited number) - May include stock procured but
of procurement agencies never supplied

Wholesalers - Only legal entity able to import - Some countries medical, dental,
medicines for distribution veterinary practitioners and
- Can provide purchase and supply pharmacists can also import
data medicines
- Supply data may be disaggregated - May be difficult to get data from
(community/hospital; by regions, private sector
facility type) - Large number of wholesalers in
- Data collection easier where some settings
limited numbers of wholesalers - May supply other smaller
- Distribution/supply data likely to wholesalers not ‘end-users’
be closer to actual consumption - Wholesalers may provide
than purchase data agriculture and veterinary sectors as
well as for human use
Donations -May be significant proportion of - May be difficult to differentiate
antimicrobials dispensed for specific donations for local population and
clinical programs special populations (migrants,
refugees)
Community - Sales from pharmacies or drug - Large number of facilities makes
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Data source Strengths Limitations

and hospital stores is closer to the actual use of data collection resource intensive
pharmacies, antimicrobials by the patients - May be difficult to collect data
drug stores - Can separate community and where only manual records exist
Dispensing hospital sectors - May be difficult to get information
data - Potentially can separate to public from private sector
and private sectors - Does not take account of
- May include some OTC medicines compliance with therapy

Health - Patient-level consumption data - May be difficult to get information

insurance data - May be disaggregated by patient from private sector
demographic characteristics - Only reimbursed antimicrobials
- Geographic data may be available reported
- Disaggregation to community and - Selected populations covered by
hospital sectors possible health insurance; may not be
- Often limited number of data representative of whole population
providers - Administrative records may not
- Data more accessible if public include all the variables of interest
sector agencies

Prescribing - May have patient characteristics, - Prescribed medicines may not be

records of diagnosis, dose, duration, co- dispensed
(health prescribed medicines - Samples of prescribers may not be
professionals representative and therefore not
or databases) reflect national data

Community, - Patient-level data will be available - Time-consuming and labour

household - Most closely reflects actual intensive to collect the data
survey data consumption - Issues of representativeness of the
- Repeat surveys can provide data collected
longitudinal data

Commercial - Standardised data collection - Data must be purchased

data sources - Capacity to combine data from - May be limited data collection in
(e.g. IMS multiple sources including some countries
Health) manufacturer records, hospital and - May not be able to examine data
pharmacy data at regional, local, facility or
prescriber level
- Use of EphMRA/PBIRG
classification rather than ATC codes
so may be limited information at the
pharmacological or chemical
subgroup level

OTC=over-the-counter
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4.3. Denominator data

The total numbers of DDDs derived as consumption estimates should be adjusted for the
population to which the data apply.

For national estimates of consumption, the appropriate population will be the total national
population (all age and gender groups combined). WHO has standardized population
estimates for all Member States. This is the default used for calculations. However, it is
possible for a country to use its own national population estimates if it is believed the WHO
estimate is not correct. National population estimates are available in the WHO Global
Observatory (http://apps.who.int/gho/data/node.main.POP107?lang=en).

4.4. Reporting metrics

The standard reporting metric for national estimates is DDDs/1000inhabitants/day (DID).

The data collection template requires entry of numbers of packages for each product
included in the register. These packages may be summed to give a total number of packages
consumed. This will provide a crude estimate of the number of courses of treatment with
antimicrobials used per year and is based on the assumption that one package = one course
of treatment. This measure needs to be interpreted carefully. In some settings, a package of
oral medicine will represent a course of treatment. In other settings, patients may buy small
numbers of tablets or capsules or dispensing is from large containers of the medicine, in
which case a package will have very little meaning. A package is not likely to be a good guide
to a course of treatment with an injectable antimicrobial.

4.5. Contextual information relating to data collection

It is important to report the sources of data used, the sectors being reported, the
antimicrobial agents included in the surveillance and to identify if there are any specific
groups of patients or facility types that have been excluded from the calculations (e.g.
nursing homes, day care centres, psychiatric facilities, rehabilitation units etc.). The
worksheet tab ‘Data Availability’ collects some descriptive data. This may be supplemented
by questionnaires or other surveys.
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5. Data management

5.1. Data flow

Within the framework of a global WHO programme on surveillance of antimicrobial

consumption, data will flow from country to the regional office and to global/ head-quarters
(Figure 2).

Figure 2 Flow of data between country, regional office and global/head-quarters

5.2. Data collection

Collection of data on antimicrobial consumption, population and questionnaires is the

responsibility of the country and its AMC national team for the surveillance programme. At
country level, protocols, forms and related documents provided by WHO might be
translated into national language. If necessary, extra documents such as training materials
may be produced by countries to facilitate the national data collection. The national data
providers may need some training on which data to collect and how to report them to the
AMC national team.
 20

The data collection process at national level can be split into different tasks according the
following points:

1. Every year, the national team sends a call for data to the data providers.
2. The data providers deliver the requested information to the national team in
the agreed format.
3. The national team checks and validates the data delivered by the data provider.
If there are issues with the data or clarifications are needed, the national team
will contact the data providers.
4. When the data are validated, the national team prepares the data for
submission to the regional office.

5.3. Data submission

Data submission involves the country, regional and global levels.

The data submission process is separated into the following steps:

1. The AMC national team submits the validated consumption data, population
data and questionnaire responses to the regional office.
2. The AMC regional team collates the data from the countries.
3. The AMC regional team validates the data at regional level with issues resolved
through consultation with national focal points.
4. The regional team submits the relevant validated data to the AMC global team
at WHO Geneva for analysis and reporting.

5.4. Data analysis

Ideally there will be capacity developed at country level to undertake the analyses of AMC
data. In the first instance, for countries new to collecting these data, the analysis will be
supported by regional and global AMC teams.

5.5. Dissemination of data

While there is Member State agreement for reporting of antimicrobial consumption

estimates at the global and regional level, the data are most useful at the country level.
Countries should share findings with all stakeholders through dissemination workshops and
other communications. There will be a need to support countries in developing appropriate
dissemination tools and preparing documents relevant for decision-makers and other
stakeholders.
 21

6. Template for Data Collection

6.1. Structure of template

The Excel template for data collection has a number of worksheets:

1. Macro These are embedded routines to assist in data checking and

export.
2. Data for each category of medicine (A07AA, D01BA, J01, J02, J04, J05,
Availability P01AB, N04BB) indicate whether the data represent the total,
community or hospital consumption
3. Product Data the key worksheet for data. A separate guidance document is
available to provide step-by-step advice on completing this
worksheet.
4. Population for each category of medicine (A07AA, D01BA, J01, J02, J04, J05,
Data P01AB, N04BB) indicate population to which the given
consumption data apply
5. ATC list of medicines being monitored, with ATC code and ATC level.
6. DDD the DDD assigned by the WHO Collaborating Centre with units of
measurement (gram, mg, MU)
7. DDD provides a list of combination medicines that have an approved
combination DDD or approved ‘unit dose’ measurement
8. Conversion a table of conversion factors from MU to grams (See Annex 4)
9. Units a description of the units used (See Annex 5)
10. Salts the specification of salts is only required for hexamine (hippurate
or mandelate) and where erythromycin data relate to the
ethylsuccinate salt.
11. RoAs routes of administration (oral, parenteral, rectal, inhalation
powder, inhalation solution). (See Annex 6)

As shown Figure 1, there are three parts to the data collection – antimicrobial consumption
data, denominator data and contextual information related to antimicrobial consumption.
The key spreadsheet for completion is the worksheet called ‘Product Data’. In this
worksheet data are entered on the antimicrobial products (medicines register) and
estimates of consumption (number of packages) that is converted into numbers of DDDs.
Population data are recorded here and population-adjusted consumption estimates are
automatically calculated by the macro. Contextual information related to antimicrobial
consumption is entered in the worksheet called ‘Data availability’.
 22

6.2. Variables

6.2.1. Variables for antimicrobial medicines register

Some countries will already have an electronic database of all antimicrobial products that
have marketing authorization (= registered products). Where such a database exists, the
relevant data can be copied into the cells of the spreadsheet.

Where there is no existing list of products, this will need to be created. This is a significant
task in Year 1. For subsequent years, the data register file can be edited and new products
added. The descriptions for products could be maintained (with zero consumption) and this
will provide an ‘historical’ file of products and consumption over the years.

The product-level variables included in the register are shown in Table 2. A full description
of the variables, data type, variable type, information and data rules and response options
are provided in Annex 3.

Table 2: Product-level data variables for the antimicrobial register

Variable name Content
COUNTRY Based on ISO 3166 alpha-3 country codes
PRODUCT_ID Unique identifier of the medicinal product package (MPP).
LABEL Medicinal product package label
PACKSIZE Size of the package
PACKSIZE_UNIT Pack size unit of measurement
PAEDIATRICS_PRODUCT * Is it a paediatric medicine product
FORM* Pharmaceutical formulation type
ROUTE_ADMIN Route of administration
STRENGTH Quantity of the main ingredient of each item
STRENGTH_UNIT Unit measurement of strength
INBASQ Basic ingredient quantity
INBASQ_UNIT Unit measurement of the basic ingredient quantity
ATC5 WHO ATC code at substance level (ATC5-level)
SALT * Salt of the active substance (hexamine, erythromycin only)
COMBINATION The WHO CC has defined DDD for combined products
PRODUCT_NAME * Medicinal product name
INGREDIENTS * Ingredient name: e.g. amoxicillin and enzyme inhibitor.
PRODUCT_ORIGIN * The product can be import, donation or locally produced.
MANUFACTURER_COUNTRY The country of the manufacturer of the product.
MANUFACTURER * Name of manufacturer
GENERIC* Is the product a generic?
CONV_FACTOR (macro) Transform strength expressed in IU into G.
WHO_DDD (macro) The DDD defined by the WHO CC for the ATC code
WHO_DDD_UNIT (macro) Unit measurement of the WHO DDD (MG, G, IU, MU, UD)
DPP (macro) DDD Per Package
Source: WHO antimicrobial medicines collection protocol year 2016
*optional variables for dataset; macro = calculated automatically by Excel macro
 23

6.2.2. Variables for consumption estimates (packages and DDDs)

The numbers of packages of each product imported/sold/dispensed are recorded. The

numbers of packages can be aggregated by the desired level of ATC code and reported as
total number of packages.

The number of packages of each product is also multiplied by the number of DDDs per
package to calculate the total numbers of DDDs for each product. The numbers of DDD are
aggregated by at the desired ATC code level to give total number of DDDs.

Consumption data may also be reported by sector – total consumption data disaggregated
to hospital and community (ambulatory care) data, or to public and private sector.

The consumption variables included in the spreadsheet are shown in Table 3. A full
description of the variables, data type, variable type, information and data rules and
response options are provided in Annex 3.

Table 3: Consumption data variables

Variable name Content
Consumption by packages
TOTAL_PACKAGES Total number of packages consumed during the year
COMMUNITY_PACKAGES Total number of packages consumed in community during the
year
HOSPITAL_PACKAGES Total number of packages consumed in hospital sector during
the year
Source: WHO antimicrobial medicines collection protocol year 2016
DDD = Defined Daily Doses

6.2.3. Variables for population estimates

The total population may be based on WHO national population estimates for the relevant
year or local estimates if there are reasons to believe WHO estimates are inaccurate.

6.2.4. Variables for population-adjusted estimates

The total numbers of packages and DDDs are divided by population estimates and the
estimates adjusted to express consumption as numbers of packages/inhabitants/year (PIY)
or numbers of DDDs/1000 inhabitants/day (DID).

6.3. Contextual information

Additional information obtained my questionnaire or survey may help with interpretation of

the consumption estimates.

The worksheet tab ‘Data Availability’ should be completed. This reports the country (3-digit
code), year of data collection, and for each class of antimicrobials under monitoring whether
the data are for total, community or hospital use.
 24

7. Glossary

Admitted patient A patient who receives hospital services and undergoes a hospital’s
formal admission process, and is thus accepted by a hospital for
inpatient care. This includes hospital-in-the-home care.

Anatomical An international system, controlled by the World Health

Therapeutic Chemical Organization Collaborating Centre for Drug Statistics Methodology,
(ATC) Classification that categorizes all medicines into one of fourteen anatomical
System groups, each of which is divided into therapeutic uses and further
subdivided into chemical subgroups.

Antimicrobial An antimicrobial is a medicine that selectively destroys or inhibits

the growth of susceptible microorganisms. Sometimes referred to
as an ‘antimicrobial agent’. Examples include antibiotics (also
known as antibacterials) antiviral and antifungal agents.

Antibiotic resistance A property of bacteria that confers the capacity to grow in the
presence of antibiotic levels that would normally suppress growth
or kill susceptible bacteria.

Antimicrobial The ability of a microorganism to grow or survive in the presence

resistance (AMR) of an antimicrobial at a concentration that is usually sufficient to
inhibit or kill microorganisms of the same species and that exceeds
concentrations achievable in the human/animal/patient.

Antimicrobial The use of co-ordinated interventions to improve and measure the

stewardship use of antimicrobials by promoting optimal drug regimen, dose,
duration and route. The aim is for optimal clinical outcome and to
limit selection of resistant strains. This is a key component of a
multi-faceted approach to preventing antimicrobial resistance.

Broad-spectrum These are effective against a wide range of bacteria. For example,
antibiotics meropenem is a broad-spectrum antibacterial.

Carbapenems Carbapenems are broad-spectrum antibiotics, often used as the

last line of treatment for hard to treat human infections caused by
Gram-negative bacteria.

Carbapenemases These are enzymes produced by bacteria which destroy

carbapenems and other beta-lactam antibiotics.

Cephalosporins Types of broad-spectrum antibiotics.

Cephalosporins – Cephalosporins like cefotaxime and cefixime are particularly active

third-generation against Gram-negative bacteria.
 25

Coverage Penetration of an intervention into the targeted population and

extent to which they access the intervention.

Disaggregated Statistics that are based on individual (that is, ungrouped) variables
— for example, separating the data by gender, age, disease state
etc.

Episode of care A period of health care with a defined start and end.

First-line treatment The preferred initial treatment of a patient at a particular stage of

their medical condition.

Generic (name) The accepted or official nonproprietary name (not a chemical

formula or a brand) by which a medicine is identified.

Gram-negative Those bacteria that do not retain crystal violet dye in the Gram-
bacteria staining procedure. They can cause many types of infection and
include E. coli and Pseudomonas aeruginosa.

Gram-positive These are bacteria that are stained dark blue or violet in the Gram-
bacteria staining procedure. They include Staphylococcus aureus and
Clostridium difficile.

Healthcare Associated Infections acquired via the provision of healthcare in either a

Infections (HCAI) hospital or community setting.
Also referred to as nosocomial infections

Multi-drug resistant Resistance to two or more antibiotics from different classes.

Meticillin-resistant A strain of Staphylococcus aureus that is resistant to beta lactam

Staphylococcus antibiotics which include penicillins (e.g. 25ethicillin and oxacillin)
aureus (MRSA) and almost all cephalosporin antibiotics. Also called multiresistant
S. aureus

‘One-Health’ Describes a coordinated, collaborative, multi-disciplinary and

approach cross-sectoral work at local, national, and global levels to attain
optimal health for people, animals and the environment.

Pathogen An infectious agent (bug or germ), a microorganism such as a virus,

bacterium, or fungus that causes disease in its host.

Prevalence The number of events of interest in a given population at a given

point in time, usually expressed as a prevalence rate i.e. as a
Also referred to as
proportion of the defined population size at that time. It includes
point prevalence
all the events of interest, both new and long standing cases.

Primary care Services provided by GP practices, dental practices, community

pharmacies and high street optometrists.
 26

Quinolones A family of antibiotics, includes broad-spectrum agents like

ciprofloxacin.

Responsible The use of antimicrobials in the most appropriate way for the
prescribing treatment or prevention of infectious disease.

Secondary care Covers acute healthcare, either elective care (planned specialist
medical care or surgery, usually following referral) or emergency
care.

Selection (of resistant The process whereby exposure to an antibiotic kills or inhibits
bacteria) sensitive bacteria, allowing resistant bacteria to increase in
number relative to the sensitive bacteria.
 27

8. Annexes

Annex 1 Introduction to ATC and DDD methodology

Annex 2 List of ATC sub-groups under surveillance

Annex 3 Variables of the register, consumption and population datasets

Annex 4 Conversion Factor List

Annex 5 Administration Route List

Annex 6 Measurement Unit List

 28

Annex 1: Introduction to ATC and DDD methodology

Categorization of medicines
The Anatomical Therapeutic Chemical (ATC) classification system is the most commonly
used method for aggregation of medicines data and allows flexibility in reporting by
medicine or groups of medicines. The classification of a substance in the ATC/DDD system is
not a recommendation for use, nor does it imply any judgements about efficacy or relative
efficacy of drugs and groups of drugs.

The first level of the code indicates the anatomical main group and consists of one letter.
There are 14 main groups as follows:

ATC Main Groups

A •Alimentary tract and metabolism

B •Blood and blood forming organs

C •Cardiovascular

D •Dermatologicals

G •Genito-urinary system and sex hormones

H •Systemic hormonal preparations,

excluding sex hormones and insulin

J •Anti-infectives for systemic use

•Antineoplastic and immunomodulating

L
agents

M •Musculo-skeletal system

N •Nervous system

•Anti-parasitic products, insecticides and

P
repellants

R •Respiratory system

S •Sensory organs

V •Various
 29

The structure and nomenclature used in the ATC classification system is illustrated for the
anti-diabetic medicine, metformin, and is shown in A1.

There are a number of challenges with the use of the ATC system. In some cases, a medicine
can be used for different indications and this is not always reflected in the ATC code. In
some cases, medicines will have several different ATC codes depending on the use of the
product, for example for systemic use or topical use.

Medicinal products containing two or more active ingredients are considered combinations
in the ATC system and have a different ATC code to the single components.

In addition, there are regular revisions of the ATC code to deal with new drugs and changes
in use of products. It is important to be aware of changes in ATC codes that may have
occurred over time when interpreting trends over time.

Box A1: The Anatomical Therapeutic Chemical (ATC) Classification system

In the Anatomical Therapeutic Chemical (ATC) classification system, the active substances
are divided into different groups according to the organ or system on which they act and
their therapeutic, pharmacological and chemical properties.
Drugs are classified in groups at five different levels. The drugs are divided into fourteen
main groups (1st level), with pharmacological/therapeutic subgroups (2 nd level). The 3rd
and 4th levels are chemical/pharmacological/therapeutic subgroups and the 5th level is
the chemical substance. The 2nd, 3rd and 4th levels are often used to identify
pharmacological subgroups when that is considered more appropriate than therapeutic
or chemical subgroups.
The complete classification of metformin illustrates the structure of the code:
A Alimentary tract and metabolism (1st level, anatomical main group)
A10 Drugs used in diabetes (2nd level, therapeutic subgroup)
A10B Blood glucose lowering drugs, excl insulins (3rd level, pharmacological
subgroup)
A10BA Biguanides (4th level, chemical subgroup)
A10BA02 Metformin (5th level, chemical substance)
Thus, in the ATC system all plain metformin preparations are given the code A10BA02.
Nomenclature
International nonproprietary names (INN) are preferred. If INN names are not assigned,
USAN (United States Adopted Name) or BAN (British Approved Name) names are usually
chosen.
WHO’s list of drug terms (Pharmacological action and therapeutic use of drugs - List of
Terms) is used when naming the different ATC levels.

ATC Codes for antimicrobial agents

The WHO Collaborating Centre for Drug Statistics Methodology has developed coding rules
for all medicines. In relation to antimicrobials, the 2016 guidelines state
(http://www.whocc.no/filearchive/publications/2016_guidelines_web.pdf )
 30

J01 ANTIBACTERIALS FOR SYSTEMIC USE

This group comprises antibacterials for systemic use, except antimycobacterials,

which are classified in J04. The antibacterials are classified according to their mode of
action and chemistry.

Combinations of two or more systemic antibacterials from different third levels are
classified in J01R, except combinations of sulfonamides and trimethoprim, which are
classified at a separate 4th level, J01EE.

Combinations of antibacterials with other drugs, including local anesthetics or

vitamins, are classified at separate 5th levels in the respective antibacterial group by
using the 50-series. Common cold preparations containing minimal amounts of
antibacterials are classified in R05X.

Inhaled antiinfectives are classified here based on the fact that preparations for
inhalation cannot be separated from preparations for injection.

Application of the ATC classification system

The anti-infective agents for systemic use are classified under ATC Main Group J (level 1).

Level 1 (Main group): ATC Main Group J (Anti-infective for systemic use)

Level 2 (pharmacological/therapeutic subgroups):

J ANTIINFECTIVES FOR SYSTEMIC USE

J01 Antibacterials for systemic use

J02 Antimycotics for systemic use
J04 Antimycobacterials
J05 Antivirals for systemic use
J06 Immune sera and immunoglobulins
J07 Vaccines
 31

Level 3 (chemical/pharmacological/therapeutic subgroups):

J01 ANTIBACTERIALS FOR SYSTEMIC USE

J01A Tetracyclines
J01B Amphenicols
J01C Beta-lactam antibacterials, penicillins
J01D Other beta-lactam antibacterials
J01E Sulfonamides and trimethoprim
J01F Macrolides, lincosamides and streptogramins
J01G Aminoglycoside antibacterials
J01M Quinolone antibacterials
J01R Combinations of antibacterials
J01X Other antibacterials

Level 4 (chemical/pharmacological/therapeutic subgroups):

J01C BETA-LACTAM ANTIBACTERIALS, PENICILLINS

J01CA Penicillins with extended spectrum

J01CE Beta-lactamase sensitive penicillins
J01CF Beta-lactamase resistant penicillins
J01CG Beta-lactamase inhibitors
J01CR Combinations of penicillins,
J01CR Combinations of penicillins, incl. beta-lactamase inhibitors

Level 5 (chemical substance):

J01CA PENICILLINS WITH EXTENDED SPECTRUM

ATC Code Name ATC Code Name

J01CA01 ampicillin J01CA12 piperacillin
J01CA02 pivampicillin J01CA13 ticarcillin
J01CA03 carbenicillin J01CA14 metampicillin
J01CA04 amoxicillin J01CA15 talampicillin
J01CA05 carindacillin J01CA16 sulbenicillin
J01CA06 bacampicillin J01CA17 temocillin
J01CA07 epicillin J01CA18 hetacillin
J01CA08 pivmecillinam J01CA19 aspoxicillin
J01CA09 azlocillin J01CA20 combinations
J01CA10 mezlocillin J01CA51 ampicillin, combinations
J01CA11 mecillinam
 32

Some examples of ATC codes

(i) Amoxicillin is J01CA04 and classified as follows:

J ANTIINFECTIVES FOR SYSTEMIC USE (Level 1)

J01 ANTIBACTERIALS FOR SYSTEMIC USE (Level 2)
J01C BETA-LACTAM ANTIBACTERIALS, PENICILLINS (Level 3)
J01CA Penicillins with extended spectrum (Level 4)
J01CA04 Amoxicillin (Level 5)

Note: J01CA04 applies to amoxicillin in all its formulations – oral, parenteral, syrup
formulations for children etc.

(ii) Ceftriaxone is J01DD04

J ANTIINFECTIVES FOR SYSTEMIC USE (Level 1)

J01 ANTIBACTERIALS FOR SYSTEMIC USE (Level 2)
J01D OTHER BETA-LACTAM ANTIBACTERIALS (Level 3)
J01DD Third generation cephalosporins (Level 4)
J01DD04 Ceftriaxone (Level 5)

(iii) Amoxicillin + clavulanic acid is J01CR02

J ANTIINFECTIVES FOR SYSTEMIC USE (Level 1)

J01 ANTIBACTERIALS FOR SYSTEMIC USE (Level 2)
J01C BETA-LACTAM ANTIBACTERIALS, PENICILLINS (Level 3)
J01CR Combinations of penicillins including beta-lactamase inhibitors (Level 4)
J01CA02 Amoxicillin and enzyme inhibitor (Level 5)

Changes of ATC Codes and new codes

ATC codes can change over time as more experience is gained with the medicine and more
products become available. The WHO ATC/DDD website provides information on alterations
to ATC codes since 1982
(http://www.whocc.no/atc_ddd_alterations__cumulative/atc_alterations/

New ATC codes can also be found on the website

(http://www.whocc.no/atc/lists_of_new_atc_ddds_and_altera/new_atc/).

Antimicrobials with multiple ATC codes

There are some antimicrobials that are classified under more than one ATC code, for
example metronidazole and vancomycin, reflecting their use in different clinical situations.

Metronidazole
 33

A01AB17 Alimentary tract and metabolism, Antiinfectives and antiseptics for local oral
treatment
D06BX01 Dermatologicals, Other chemotherapeutics
G01AF01 Genitourinary system and sex hormones, Imidazole derivatives
J01XD01 Antiinfectives for systemic use, Imidazole derivatives
P01AB01 Antiparasitic products, insecticides and repellants, Nitroimidazole derivatives
P01AB51 Antiparasitic products, insecticides and repellants, Nitroimidazole derivatives,
metronidazole combinations

Vancomycin
A07AA09 Alimentary tract and metabolism, Intestinal antiinfectives
J01XA01 Antiinfectives for systemic use, Other antibacterials, Glycopepeptide
antibacterials

To determine total use of each of these antimicrobials, it will be necessary to include all the
relevant ATC codes.

Defined Daily Dose (DDD)

The most commonly used measure for reporting of drug utilization is numbers of Defined
Daily Doses (DDDs) where the DDD is the assumed average maintenance dose per day for a
drug used for its main indication in adults. A DDD is only assigned for drugs that already
have an ATC code. Converting aggregate quantities to DDDs allows a rough estimation of the
potential treatment days of the pharmaceutical are procured or consumed. The DDD,
however, is only a technical unit of use and does not necessarily reflect the recommended
or average prescribed dose.

The DDDs for the anti-infectives are as a main rule based on the use in infections of
moderate severity. However, some anti-infective are only used in severe infections and their
DDDs are assigned accordingly.

Generally, DDDs assigned are based on daily treatment. However, in the case of
antimicrobial agents there are rules to guide calculation of the DDD based on the duration
of the treatment.

For anti-infective given in a high initially starting dose followed by a lower daily
"maintenance" dose, the DDDs are based on the "maintenance" dose if the total duration of
the treatment course is more than one week.

If, however, the treatment course is 7 days or less, the DDDs are assigned according to the
average daily dose i.e. the total course dose divided by the number of treatment days.

Example of calculation of DDD for antimicrobial agent

 34

Substance M: 1000mg on the first day, then 500mg daily. Duration of therapy: 14 days
DDD is 500mg
Substance M: 1000mg on the first day, then 500mg daily. Duration of therapy: 5 days
DDD is 600mg ((1000 + 4x500)/5 = 600mg)

Note: the DDD is a technical unit of measurement and it may or may not reflect the doses
that are prescribed and used in practice. The prescribed daily dose (PDD) is the average daily
dose prescribed and is obtained from a representative sample of prescriptions.
The DDD remains a useful metric as it is a standardized measure and can be applied to all
data. It is important to think about possible differences with prescribed daily doses when
interpreting the results of the analysis.

Returning J01CA Penicillins with extended spectrum, the DDD values assigned in 2016 are:

ATC Code Name DDD Unit of DDD Administration route

J01CA01 ampicillin 2 g O
2 g P
2 g R
J01CA02 pivampicillin 1.05 g O
J01CA03 carbenicillin 12 g P
J01CA04 amoxicillin 1 g P
1 g O
J01CA05 carindacillin 4 g O
J01CA06 bacampicillin 1.2 g O
J01CA07 epicillin 2 g O
2 g P
J01CA08 pivmecillinam 0.6 g O
J01CA09 azlocillin 12 g P
J01CA10 mezlocillin 6 g P
J01CA11 mecillinam 1.2 g P
J01CA12 piperacillin 14 g P
J01CA13 ticarcillin 15 g P
J01CA14 metampicillin 1.5 g O
1.5 g P
J01CA15 talampicillin 2 g O
J01CA16 sulbenicillin 15 g P
J01CA17 temocillin 2 g P
J01CA18 hetacillin 2 g O
J01CA19 aspoxicillin 4 g P
J01CA20 combinations
J01CA51 ampicillin, combinations
DDD = defined daily dose; g = gram; O=oral; P=parenteral
 35

Note that there are three DDD values for ampicillin, and two each for amoxicillin, epicillin
and metampicillin. In this case, the DDDs remain the same for oral and parenteral
administration although this is not the case for all antimicrobials.

Some examples of where the DDD changes according to the formulation are shown in the
following table:

ATC Code Name DDD Unit of Administration

DDD route
J01CR02 amoxicillin and enzyme inhibitor 1 g O
3 g P
J01FA01 erythromycin 1 g O
erthyromycin ethylsuccinate 2 g O
1 g P
J01MA02 ciprofloxacin 1 g O
0.5 g P
J01GB01 tobramycin 0.112 g Inhal. powder
0.3 g Inhal. solution
0.24 g P
P01AB01 metronidazole 2 g O
P01AB01 metronidazole 2 g R
J01XD01 metronidazole 1.5 g P
DDD = defined daily dose; g = gram; O=oral; P=parenteral; inhal=inhalation; R=rectal

Notes:
1. The DDD for amoxicillin and enzyme inhibitor is the same as the DDD for amoxicillin
alone. The DDD for the combination is based on the main active ingredient.
2. Erythromycin ethylsuccinate has a special code for salt (ESUC) in the data collection
template so that the correct DDD is applied.
3. The different DDD values for ciprofloxacin, tobramycin and metronidazole are
assigned in the template according to whether the product is for oral, parenteral,
inhalation or rectal administration.
4. In the case of metronidazole, J01 only includes the forms for parenteral
administration. For total use of metronidazole, it will be necessary to use all the
relevant ATC codes. Data for P01AB01 are included in the AMC template.

If there is no ATC code available or there is no DDD assigned for product, contact the
Regional AMC team for advice.
 36

Annex 2: List of ATC sub-groups under surveillance

Code Name Core set

A07AA Antibiotics Mandatory
D01BA Antifungals for systemic use Optional
J01AA Tetracyclines Mandatory
J01BA Amphenicols Mandatory
J01CA Penicillins with extended spectrum Mandatory
J01CE Beta-lactamase sensitive penicillins Mandatory
J01CF Beta-lactamase resistant penicillins Mandatory
J01CG Beta-lactamase inhibitors Mandatory
J01CR Combinations of penicillins, incl. beta-lactamase inhibitors Mandatory
J01DB First-generation cephalosporins Mandatory
J01DC Second-generation cephalosporins Mandatory
J01DD Third-generation cephalosporins Mandatory
J01DE Fourth-generation cephalosporins Mandatory
J01DF Monobactams Mandatory
J01DH Carbapenems Mandatory
J01DI Other cephalosporins and penems Mandatory
J01EA Trimethoprim and derivatives Mandatory
J01EB Short-acting sulfonamides Mandatory
J01EC Intermediate-acting sulfonamides Mandatory
J01ED Long-acting sulfonamides Mandatory
J01EE Combinations of sulfonamides and trimethoprim, incl. derivatives Mandatory
J01FA Macrolides Mandatory
J01FF Lincosamides Mandatory
J01FG Streptogramins Mandatory
J01GA Streptomycins Mandatory
J01GB Other aminoglycosides Mandatory
J01MA Fluoroquinolones Mandatory
J01MB Other quinolones Mandatory
J01RA Combinations of antibacterials Mandatory
J01XA Glycopeptide antibacterials Mandatory
J01XB Polymyxins Mandatory
J01XC Steroid antibacterials Mandatory
J01XD Imidazole derivatives Mandatory
J01XE Nitrofuran derivatives Mandatory
J01XX Other antibacterials Mandatory
J02AA Antibiotics Optional
J02AB Imidazole derivatives Optional
J02AC Triazole derivatives Optional
J02AX Other antimycotics for systemic use Optional
 37

J04AA Aminosalicylic acid and derivatives Optional

J04AB Antibiotics Optional
J04AC Hydrazides Optional
J04AD Thiocarbamide derivatives Optional
J04AK Other drugs for treatment of tuberculosis Optional
J04AM Combinations of drugs for treatment of tuberculosis Optional
J05AA Thiosemicarbazones Optional
J05AB Nucleosides and nucleotides excl. reverse transcriptase inhibitors Optional
J05AC Cyclic amines Optional
J05AD Phosphonic acid derivatives Optional
J05AE Protease inhibitors Optional
J05AF Nucleoside and nucleotide reverse transcriptase inhibitors Optional
J05AG Non-nucleoside reverse transcriptase inhibitors Optional
J05AH Neuraminidase inhibitors Optional
J05AR Antivirals for treatment of HIV infections, combinations Optional
J05AX Other antivirals Optional
P01AB Nitroimidazole derivatives Optional
P01BA Aminoquinolines Optional
P01BB Biguanides Optional
P01BC Methanolquinolines Optional
P01BD Diaminopyrimidines Optional
P01BE Artemisinin and derivatives, plain Optional
P01BF Artemisinin and derivatives, combinations Optional
P01BX Other antimalarials Optional
N04BB Adamantane derivatives Optional
 38

Annex 3: Variables of the register and consumption datasets

WHO is providing an excel file for collecting the antimicrobial consumption data to the
participating countries. The excel file contains all the variables mentioned below plus two
additional ones, “Status” and “Status Message”. The excel file contains macros than will
automatically populate some of the variables (including the “Status” and “Status Message”)
when the macro ‘Validate Products’ is run. For each of the variables listed below, it is
mentioned if they are automatically filled in by the macro. If the participants do not use the
provided excel file, they have to populate all variables manually.

Variables for the ‘Product data’ worksheet

Variable COUNTRY
Description Three letter code uniquely identifying the reporting country.
Data type Coded Value
Variable type Mandatory
Information List of country codes based on the ISO3166 alpha-3 country codes
list (ref: https://en.wikipedia.org/wiki/ISO_3166-1_alpha-3)
Variable PRODUCT_ID
Description The national code of the Medicinal Product Package. The code
uniquely identifying the medicinal product package (MPP) for the
country.
Data type Text
Variable type Mandatory
Information The Product_ID should not change over time. When a MPP is no
longer available on the market or is no longer registered, its
Product_ID should not be attributed to another MPP in order to
identify the old MPP for historical purposes (prescription history).
If no code exists for a MPP, the country should provide one
arbitrary code that should uniquely identify the MPP.
Variable LABEL
Description The label of the MPP. The label should contains if possible name
of the medicinal product, package size, strength and
pharmaceutical form
Data type Text
Variable type Mandatory
Information The label is an important variable as it is the only information that
allows cross check of the medicinal product package for an
external reviewer.
Variable PACKSIZE
Description The package size of the MPP. The size of the MPP can be reported
as a number of pieces in the MPP or as a number of mL.
 39

Data type Number

Variable type Mandatory
Information For MPP that are administrated as liquid form (i.e. syrup), the
package size should be reported as mL of final reconstituted
product. For all other pharmaceutical forms, the package size
must be reported as a number of pieces. For instance, for vials,
the package size must be reported as a number of vials in the
package and not as the volume of reconstituted product.
Variable PACKSIZE_UNIT
Description The unit of the package size of the MPP.
Data type Coded Value (see Measurement Unit List in annex)
Variable type Mandatory
Information The measurement unit in which is expressed the package size of
the MPP.
Variable PAEDIATRIC_PRODUCT
Description The MPP is a paediatric MPP
Data type YES/NO
Variable type Optional
Information The product is a paediatrics product or not.
Variable FORM
Description The pharmaceutical form of the MPP.
Data type Text
Variable type Optional
Information
Variable ROUTE_ADMIN
Description The route of administration of the MPP.
Data type Coded Value (see Administration route List in annex)
Variable type Mandatory
Information The route of administration is used to attribute a DDD to the MPP
and to report consumption according to the route of
administration.
Variable STRENGTH
Description The strength of the substance of each item as defined by
PACKSIZE. For multi-ingredient products this field should contain
the strength in which the DDD is expressed.
Data type Number
Variable type Mandatory
Information For some specific substances used in combination with others, the
WHO CC has defined some rules such as to only take into account
the antimicrobial substance and not the combined substance (e.g.
amoxicillin/clavulanic acid). For products with multiple
antimicrobial substances, the WHO CC has defined DDD for
combined products. In this case, the strength should be reported
in the same unit as the DDD for the corresponding combined
 40

product.
Variable STRENGTH_UNIT
Description The unit of the strength of the MPP.
Data type Coded Value (see Measurement Unit List in annex)
Variable type Mandatory
Information The measurement unit in which is expressed the strength of the
MPP.
Variable INBASQ
Description The basic ingredient quantity (INBASQ) used for describing
concentration of fluids (e.g. 200 mg/10 ml). In syrups and
solutions INBASQ describes the denominator part of the strength.
In all other cases (including perfusion fluids or ampullas), the
INBASQ should be set to 1.
Data type Number
Variable type Mandatory
Information The default value is 1 when the package size is not expressed in
ML

Variable INBASQ_UNIT
Description The unit of the INBASQ of the MPP.
Data type Coded Value (see Measurement Unit List in annex)
Variable type Mandatory
Information The measurement unit in which is expressed the basic ingredient
quantity of the MPP.
Variable ATC5
Description The WHO ATC code at substance level (ATC 5th level) of the MPP
Data type Coded Value
Variable type Mandatory
Information Each ATC code is linked to its product main therapeutic use. The
ATC5 variable is used to attribute a DDD to the MPP and to report
antimicrobial consumption according to the ATC classification. See
ATC classification at ATC 4th level in annex.
Variable SALT
Description The code of the salt associated to the active substance.
Data type Coded Value
Variable type Optional
Information It is only valid for methenamin (J01XX05) and erythromycin
(J01FA01), for all other substances, the salt should not be
specified. The reason is that the WHO CC has defined DDD
depending on the salt for these two substances only.
Variable COMBINATION
Description The code of the combined product of the MPP
Data type Coded Value (see Combined Product List in annex)
Variable type Optional
 41

Information If the MPP is a combined product with a corresponding entry in

the Combined Product list, the variable must be set in order to
attribute the correct DDD to the MPP. In addition if the variable is
set, the strength unit should be reported in Unit Doses.
Variable PRODUCT_NAME
Description The name of the product.
Data type Text
Variable type Optional
Information The name of the product. The name should be common to all
MPPs of the same product.
Variable INGREDIENTS
Description The name of the ingredients in the MPP, not only the
antimicrobial substances.
Data type Text
Variable type Optional
Information INN names should be used to report the ingredients.
Variable PRODUCT_ORIGIN
Description The source of the product.
Data type Coded Value
Variable type Optional
Information The source of the product can be import, donation, locally
produced.
Variable MANUFACTURER_COUNTRY
Description Three letter code uniquely identifying the country of
manufacturing.
Data type Coded Value
Variable type Optional
Information See COUNTRY variable
Variable MANUFACTURER
Description The name of marketing authorization number of the MPP.
Data type Text
Variable type Optional
Information
Variable GENERICS
Description The MPP is a generic.
Data type YES/NO
Variable type Optional
Information
Variable CONV_FACTOR
Description the conversion factor to transform strength expressed in IU into
strength expressed in G.
Data type Number
Variable type Macro enters data in this cell automatically
 42

Information If there is no need to convert from IU to G, CONV_FACTOR must

be set to 1.
See Conversion Factor List for the list of existing conversion
factors.
If strength is expressed in IU and DDD in G and no conversion
factor exists, no DDD per MPP will be calculated and no
consumption for this MPP will be reported. See Conversion factor
list in annex.
Variable PACKCONTENT
Description The content of active substance the MPP.
Data type Number
Variable type Macro enters data in this cell automatically
Information The package content of the MPP is calculated by multiplying the
package size by the strength and dividing by the INBASQ.
Variable PACKCONTENT_UNIT
Description The unit of the package content of the MPP.
Data type Coded Value (see Measurement Unit List in annex)
Variable type Macro enters data in this cell automatically
Information The measurement unit in which is expressed the package content
of the MPP.
Variable ARS
Description A code combining the ATC code (A), the route of administration
code (R) and the optional Salt code (S)
Data type Character
Variable type Macro enters data in this cell automatically
Information The ARS code identified uniquely the DDD to be assigned to the
product. Note that when a combination code is entered, the DDD
for this product will be picked up using the combination code.
Variable WHO_DDD
Description The official WHO DDD of the MPP.
Data type Number
Variable type Macro enters data in this cell automatically
Information The WHO DDD is assigned according to the ATC5, ROUTE_ADMIN,
COMBINATION and SALT variables.
Some MPP will not have corresponding WHO DDD. In this case, if
no national DDD exists, no DDD per MPP will be calculated and no
consumption for this MPP will be reported.
Variable WHO_DDD_UNIT
Description The unit of the WHO DDD of the MPP.
Data type Coded Value (see Measurement Unit List in annex)
Variable type Macro enters this cell automatically
Information The measurement unit in which is expressed the WHO DDD of the
MPP.
Variable DPP
 43

Description The number of calculated DDD in the MPP.

Data type Number
Variable type Macro enters data in this cell automatically
Information If a CALC_DDD has been assigned, the DPP will be calculated for
the MPP.
The overall number of sold DDD for the MPP will be calculated by
multiplying the DPP by the number of packages sold.
Variable TOTAL_PACKAGES (previously T_PACKAGES)
Description The total number of packages of the MPP / Product_ID
Data type Number
Variable type
Information
Variable COMMUNITY_PACKAGES (previously C_PACKAGES)
Description The number of packages of the MPP / Product_ID for community
use.
Data type Number
Variable type
Information
Variable HOSPITAL_PACKAGES (previously H_PACKAGES)
Description The number of packages of the MPP / Product_ID for hospital use.
Data type Number
Variable type
Information
 44

Annex 4: Conversion factor List

ATC5 Administration From To Factor

Route
J01CE01 P MU G 0.6
J01CE02 O MU G 0.625
J01FA02 O MU G 0.3125
J01CE08 P MU G 0.6
J01CE09 P MU G 1

Annex 5: Administration Route List

Code Name
O Oral
P Parenteral
R Rectal
IP Inhalation powder
IS Inhalation solution

Annex 6: Measurement Unit List

Code Name
MG Milligram
G Gram
IU International unit
MU Millions of international unit
UD Unit dose
PCS Piece
ML Millilitre