SUMMARY OF THE INTERNATIONAL CLINICAL GUIDELINES FOR THE

MANAGEMENT OF HOSPITAL-ACQUIRED AND VENTILATOR-ACQUIRED

PNEUMONIA

OLIVIA DES VINCA A.N

DEPARTEMEN ANESTESI DAN TERAPI INTENSIF

FAKULTAS KEDOKTERAN
UNIVERSITAS PADJAJARAN

PEMBIMBING : DR.dr.Erwin Pradian,Sp.An,MARS,KIC,KRA

 BACKGROUND
Recently, the ERS, ESICM, ESCMID and ALAT published clinical guidelines on the therapeutic and
management strategies for adult patients with HAP and VAP, designed to guide clinical decisions
made not only by pulmonologists and intensivists but by all health professionals who treat these
patients
 The clinical guidelines are Evidence-based (Grading of Recommendations Assessment, Development
and Evaluation) and follow the PICO (population-intervention-comparison-outcome) model.

 In addition, important differences between approaches in Europe and the USA have been
apparent.
 BACKGROUND

Nosocomial Pneumonia

“develops in hospitalised patients after 48 h of admission, and does not

HAP require (but may include) artificial ventilation at the time of diagnosis”

VAP “which occurs in intensive care unit (ICU) patients who have received
mechanical ventilation for at least 48 h”

“Both types of pneumonia lengthen hospital stay and consume considerable health resources”
 OBTAINING SAMPLES IN INTUBATED
PATIENTS
• To identify the causative agent of nosocomial pneumonia, the recommendation is to perform a
qualitative or quantitative (preferred) analysis of the respiratory secretions

 Quantitative analyses use the

bacteriological growth count to assist
differentiation between infection and
colonisation
 Qualitative cultures of tracheal
aspirates are simple and noninvasive
 OBTAINING SAMPLES IN INTUBATED
PATIENTS
 Both invasive techniques (fibre-optic bronchoscopy or mini-bronchoalveolar lavage) and non-
invasive techniques can be used to obtain samples of respiratory secretions for quantitative or
qualitative analysis.
1. Quantitative analyses use the bacteriological growth count to assist differentiation between infection
and colonisation

2. Qualitative cultures of tracheal aspirates are simple and noninvasive, but have limitation  that
samples are often contaminated by the flora colonising the upper tracts and are less specific.

Non-invasive methods : may overestimate the presence of bacteria in the initial examination of the
samples, which can lead to excessive antibiotic use , however a negative result may also indicate
that the infection has been controlled.
 OBTAINING SAMPLES IN INTUBATED
PATIENTS

 European guideline indicate  is preferable to obtain the distal quantitative samples before antibiotic
treatment, since it is known that if samples are obtained within 48 h of the start of antibiotic treatment the
result may be altered or emerge as negative.

 In the view of the general overuse antibiotics  the reduction in their prescription through use of distal
quantitative cultures may have a positive impact on the appearance of resistance and consequently on health
expenditure , although no studies of cost effectiveness have been carried out to date
TREATMENT OF EARLY AND LATE NOSOCOMIAL
PNEUMONIA
The distinction of HAP/VAP
treatment should be made :

Patients with risk

factors for antibiotic Early nosocomial
resistance pneumonia

Patients without the Late nosocomial

risk patients pneumonia
TREATMENT OF EARLY AND LATE NOSOCOMIAL
PNEUMONIA
EARLY NOSOCOMIAL PNEUMONIA LATE NOSOCOMIAL PNEUMONIA
Do not have risk factors for multidrug resistance Present risk factors for multi drug resistance

Have a low mortality risk Have a high risk of mortality

Treated in an ICU with a low rate of MDR pathogens Initial broad spectrum empirical should be performed

Should be treated with antibiotics that cover In later case, a combination of antibiotics should be
community pathogens prescribed in order to expand the spectrum and avoid
resistance
The most frequent causative pathogens : The causative agents are at high risk for antibiotic
Streptococcus pneumonia, Haemophilus influenza, resistance ; for example : Pseudomonas aeuroginosa,
Methicillin-sensitive Staphylococcus aureus Acitenobacter baumanii, Methicillin-resistant S.aureus
(MRSA) and other Gram-negative bacilli, depending on the
predominant microorganism in each hospital and ICU
TREATMENT OF EARLY AND LATE NOSOCOMIAL
PNEUMONIA

 Late onset pneumonia develop after 5 days of hospitalization

 Prior antimicrobial therapy or hospitalisastion for longer than 2
days during the 3 months prior to the episode .
 Advanced age and previous use of antibiotics
The important
variable for  Patients over 65 years of age are at a greater risk of infection
indetifying MDR with methicillin-resistant Staphylococcus aureus.
pathogens
 Acute renal failure  associated with an increased risk of
Community Acquired Pneumonia (CAP) due to Pseudomonas
aeruginosa, Enterobacteria producing extended spectrum B-
lactamase (ESBL) and multidrug resistance
TREATMENT OF EARLY AND LATE NOSOCOMIAL
PNEUMONIA
 TREATMENT OF EARLY AND LATE NOSOCOMIAL
PNEUMONIA
The selection of patients with early-onset nosocomial pneumonia to receive empirical treatment with

narrow-spectrum antibiotics should be based on :

1. Individual risks
2. The severity of the clinical situation (shock)
3. The frequency and type of MDR pathogens detected in the ICU

*) Narrow-Spectrum Antibiotics  early onset of HAP or VAP, whenever the risk of resistance and mortality is considered to be low

*) Broad-Spectrum Empirical treatment against P. aeruginosa and ESBL producing organisms  early-onset HAP/VAP who
develop septic shock. In addition : MRSA should be covered if prevalent in the unit (25% S aureus in the unit).

*) Multiple broad-spectrum antibiotics should not be used routinely, in order to prevent drug-related toxicities, such as renal
failure due to the use of nephrotoxic drugs aminoglycosides and vancomycin , but may be necessary in selected patients.
 ONE OR TWO ANTIBIOTICS FOR INITIAL BROAD-
SPECTRUM EMPIRICAL TREATMENT
Aims of Combined Antibiotic Treatment :
 To obtain synergies between different groups of antibiotics, extending the spectrum of action against Gram-negative bacilli
and avoiding the emergence of resistance.
 However , combined treatments may also have disadvantages (at least potentially) such as the increased toxicity, the higher
cost of treatment and problems of superinfection.
 ONE OR TWO ANTIBIOTICS FOR INITIAL
BROAD-SPECTRUM EMPIRICAL TREATMENT

It is important to start combined empirical treatment if there is a high risk of HAP/VAP due to
MDR Gram-negative bacilli, and the patient has septic shock.

If there is a high risk of MRSA in the unit , a specific antibiotic directed at this pathogen shoud be
added.

If combined therapy is started, it should be continued in the presence of pan-resistant or MDR
non-fermenting Gram-negative bacteria or carbapenem-resistant Enterobacteria isolates .

Combined therapy may be changed to monotherapy depending on the results of the cultures.
 DURATION OF TREATMENT

Current Recommendation : to use 7–8 day treatments in patients with VAP without other respiratory
comorbidities ( pulmonary empyema, lung abcess, cavitation or necrotising pneumonia) , and who
present a good response to treatment in order to avoid the appearance of multidrug resistance.

The European guidelines argue against routine antibiotic therapy for more than 3 days in patients
with a low probability of HAP and no clinical deterioration within 72 h of symptom onset

“The duration of antibiotic treatment in HAP is a controversial point that has triggered spirited debate”
 CLINICAL ASSESSMENT OR DETECTION OF
BIOMARKERS AS A PREDICTOR OF RESPONSE

Several biomarkers for nosocomial pneumonia have been determined, including C-reactive
protein, procalcitonin (PCT), copeptin and the mid-regional pro-atrial natriuretic peptide

PCT alone is the greatest predictor of mortality risks

Biomarkers such as copeptin and the SOFA score can predict mortality in patients with VAP

CPIS is a semi-objective evaluation of several clinical factors of pneumonia

 To identify patients with VAP who might respond to treatment concluded that serial CPIS measurements might

define the clinical course of VAP, identifying patients with a good response after 3 days from the diagnosis
 PCT AS A MARKER OF TREATMENT DURATION IN
PATIENTS WITH NOSOCOMIAL PNEUMONIA WITH
SEVERE SEPSIS OR VAP

Although PCT may be limited as a marker of treatment response, it has been abundantly studied
and it is the most common biomarker evaluated in daily clinical practice.

Study Conducted In China with

A Meta-Analysis & A Cochrane The European Guidelines
Review 115 critically ill patients with VAP

The use of clinical algorithms based on High PCT levels were associated with Serial measurement of PCT serum
PCT levels produce a significant an increased risk of mortality within 2 levels can be performed together with
reduction in antibiotic consumption months of diagnosis clinical assessment in specific clinical
without increasing mortality rates or circumstances in order to shorten the
treatment failure duration of antibiotic treatment
 PCT AS A MARKER OF TREATMENT DURATION IN
PATIENTS WITH NOSOCOMIAL PNEUMONIA WITH
SEVERE SEPSIS OR VAP

 The European guidelines  serial measurement of PCT serum levels can be performed together with clinical
assessment in specific clinical circumstances in order to shorten the duration of antibiotic treatment.
 Since the expected duration of antibiotic treatment in patients with HAP/VAP is 7–8 days, performing serial
determinations of PCT levels has marginal effects on shortening antibiotic treatment in patients with a good response
to initial treatment
 Neither the initiation nor the duration of antibiotic treatment should depend solely on biomarkers.
 TOPICAL APPLICATION OF NON-ABSORBABLE
ANTIMICROBIALS IN PATIENTS UNDERGOING MECHANICAL
VENTILATION FOR MORE THAN 48 H


The oral flora of patients admitted to the hospital rapidly shifts to a predominance of aerobic Gram-negative
pathogens that can be aspirated into the lower respiratory tract, ultimately resulting in the development of
pneumonia
 Therefore, appropriate hygiene of the oral cavity of hospitalised patients is mandatory


SOD (with non-absorbable topical antibiotics) and SDD (with administration of non-absorbable topical
antibiotics in the oropharynx and gastrointestinal tract, and intravenous antibiotics) may be associated with
reductions in nosocomial pneumonia and death

NOTE:
SOD = Selective Oral Decontamination
SDD = Selective Digestive Deconatmination
 TOPICAL APPLICATION OF NON-ABSORBABLE
ANTIMICROBIALS IN PATIENTS UNDERGOING MECHANICAL
VENTILATION FOR MORE THAN 48 H

The European guidelines  do not make any recommendations on the use of chlorhexidine for
performing SOD in patients requiring mechanical ventilation.

There are no major differences between benefits associated with SOD and SDD :
 Therefore, the European guidelines recommend the use of SOD rather than SDD, especially in
environments with low resistance rates and low antibiotic consumption, in order to avoid the use of
supplementary intravenous antibiotics
 TREATMENT RATIONAL FOR RISK FACTORS (MDR PATHOGENS)
IN EUROPEAN AND AMERICAN GUIDELINES

AMERICAN EUROPEAN
Exposure to antibiotics Local ICU Ecology
 Time in Hospital  25% MDR
 Hospitalization prior to the occurance of VAP
 Other factors asscociated to the organ failure of the Severity
host :

CV- Septic Shock

 The probability of dying increased by 15% in
Respiratory-ARDS septic shock patients and the ecology
Renal –CRRT prior VAP onset
 MAIN DIFFERENCES FOR THE EUROPEAN AND AMERICAN
GUIDELINES RECOMMENDATIONS
AMERICAN EUROPEAN
PREVENTION
 Absence of recommendation  Not to issue a recommendation on chlorhexidine
 Society for Healthcare and Epidemiology of America  SOD, but not SDD, in settings with low rates of
(SHEA) antibiotic-resistant bacteria

DIAGNOSIS

 To perform non-invasive samples, rather than being  Distal quantitative samples to reduce antibiotic
treated empirically exposure and to improve the accuracy of the results

TREATMENT

 Organ Failure
 Shock
 Antibiotic exposure
 Target combination and adjunctive inhaled if failure  Local ICU ecology
 Combination Empirical if both above
 MAIN DIFFERENCES FOR THE EUROPEAN AND AMERICAN
GUIDELINES RECOMMENDATIONS

AMERICAN EUROPEAN
MICROBIOLOGIC METHODS TO DIAGNOSE
 Recommended to use non-invasive sampling and
semiquantitatives culture to diagnose VAP  The use invasive quantitative samples (prior to any
antibiotic treatment), in order to reduce antibiotic
exposure in stable patients with suspected VAP and
to improve the accuracy of the results.

THE USE OF BIOMARKERS AND THE CLINICAL PULMONARY INFECTION SCORE TO DIAGNOSE
 Recommended using clinical criteria alone, rather  Routinely performing biomarker determination into
than using serum PCT plus clinical criteria, to decide the daily clinical assessment in patiens receiving
whether or not to initiate antibiotic therapy. treatment for nosocomial pneumonia either
 Not using the CPIS to guide the discontinuation of ventilated or not to predict late treatement failure
antibiotic therapy.  CRP, PCT, Copeptin, and MR-pro-ANP.
 MAIN DIFFERENCES FOR THE EUROPEAN AND AMERICAN GUIDELINES
RECOMMENDATIONS
AMERICAN EUROPEAN
SINGLE VS COMBINATION FOR INITIAL TREATMENT (EMPIRIC THERAPY)
 Recommended that empiric treatment regiments be
informed by the local distribution of pathogens
asscociated with VAP and their antimicrobial  The first consideration in choosing an empiric therapy is
susceptibilities whether the patient is at high or low risk for both MDR
pathogen infection and mortality.
 Recommendation for combination was mainly Low risk :
related to target therapy and de-escalation Using monotherapy than combination therapy when treating
serious infection.
For those, low risk  recommended empiric therapy is a narrow
–spectrum agent with activity against non resistant Gram-
negative and MRSA.

High risk (At risk for MDR pathogens and /or >15% mortality
risk ) :
Initial empiric therapy is determined by whether the patient is in
septic shock or not.
Empirical treatment with combination was recommended in
patients with septic shock.
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