• Summary
  Click here to print a Quick Reference Guide
• Background
• Clinical Diagnosis
• Investigation
• Treatment
• Non-Antimicrobial Treatment
• Empirical Antimicrobial Treatment
• Directed Antimicrobial Treatment (when microbiology results are known)
• Duration of Treatment
• Switch to oral agent(s)
• Treatment Failure

Criteria for use of guidelines:
VAP should be considered in ventilated patients [>48h] with:
New or progressive infiltrates on chest x-ray consistent with pneumonia AND ≥2 of:

• Purulent respiratory secretions
• Increasing oxygen requirement
• Fever ≥38^oC or hypothermia <36^oC
• White cell count >12 or <4 x 10⁹L

Investigations required

• Chest x-ray
• Bronchoalveolar lavage [bronchoscopic or “blind”, not endotracheal secretions]
• Blood cultures
• Consider Legionella urinary antigen
• Full blood count, Urea and electrolytes, C-reactive protein

Non-Antimicrobial Management
As directed by consultant in intensive care and ventilator care bundles.

Antimicrobial treatment
See algorithm or full guideline

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Ventilator-associated pneumonia [VAP] is a form of hospital acquired pneumonia. VAP is defined as pneumonia developing at least 48 hours after implementing endotracheal intubation and/or mechanical ventilation that was not present before intubation (Masterton et al., 2008). VAP is a serious healthcare associated infection with a mortality rate between 24-76% depending on the pathogen involved (Masterton et al., 2008). VAP is not uncommon and accounts for a quarter of intensive care unit infections (Masterton et al., 2008).

The lack of gold standard for the diagnosis of VAP has made assessment of diagnostic and treatment strategies problematic (Anon, 2005; Masterton et al., 2008). However, in practical terms, VAP can be classified as early or late onset. This classification has relevance to the causative organism and therefore to empirical therapy. In this guideline early onset VAP is defined as that developing within four days of hospital admission and late onset VAP is defined as that occurring after five days or more (Anon, 2005). The risk of developing VAP is highest in the first five days of ventilation.

The microbiology of VAP is complex. In early onset VAP, the usual pathogens associated with community acquired pneumonia and more sensitive hospital acquired bacteria predominate e.g. Escherichia coli, Klebsiella spp. Streptococcus pneumoniae and meticillin sensitive Staphylococcus aureus. In late onset VAP multi-resistant pathogens become more prominent including meticillin resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing coliforms, Pseudomonas aeruginosa and Acinetobacter spp.

This guideline is concerned with the management of VAP, not its prevention which is the subject of ventilation care bundles.

Patients who develop pneumonia <48 hours after intubation or who already have pneumonia at the time of intubation should be treated according to the LTHT community acquired pneumonia guidelines or LTHT hospital acquired pneumonia guidelines as appropriate.

Aspects of this guideline may not be appropriate for neutropenic or severely immunocompromised patients who should be discussed with a microbiologist.

These are guidelines and an alternative approach may be necessary in individual cases following discussion with a microbiologist.

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VAP should be considered in ventilated patients [>48h] with:
New or progressive infiltrates on chest x-ray consistent with pneumonia AND ≥2 of:

• Purulent respiratory secretions
• Increasing oxygen requirement
• Fever ≥38^oC
• White cell count >12 or <4 x 10⁹L

Evidence level D [this is a synthesis of level C evidence (Anon, 2005; Masterton et al., 2008)]

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Chest X-ray.
Diagnosis requires a chest x-ray. [Evidence level C]

Respiratory tract sampling for microbiology
Endotracheal aspirates or sputum samples are not recommended for the diagnosis of VAP (Masterton et al., 2008) [Evidence level A]

Bronchoalveolar lavage [BAL] samples, whether “blind” or derived via bronchoscopy are equally useful in the microbiological diagnosis of VAP. Either method can be used in suspected cases of VAP (Masterton et al., 2008) [Evidence level A].

Quantitative cultures of BAL samples do not improve the diagnosis of VAP. (Masterton et al., 2008). [Evidence level A]

BAL samples will have direct microscopy and be cultured semi-quantitatively: a heavy [+++] “pure” culture of a recognized pathogenic bacterial species should be considered as likely to be significant in the appropriate clinical setting. Other result should be interpreted with caution. [Evidence level D]

Blood cultures
“All patients with suspected VAP should have Blood cultures collected, recognizing that a positive result can indicate the presence of either pneumonia or extrapulmonary infection” [Evidence level B] (Anon, 2005)

Other microbiology samples
Legionella urinary antigen testing should be undertaken when there is a clinical suspicion of Legionnaires disease. [Evidence level D]

Full blood count
A full blood count is indicated because a raised peripheral white blood cell count may support a diagnosis of VAP. [Evidence level C]

Clinical chemistry
Blood sampling for urea and electrolytes is recommended to monitor renal function. [Evidence level C]

Recommendations regarding CRP measurement do not appear in current guidelines (Anon, 2005; Masterton et al., 2008) but local opinion is that a normal CRP would be very unlikely in a case of VAP. CRP should be measurement at baseline and to monitor response to therapy is recommended. [Evidence level D]

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As directed by consultant in intensive care and ventilator care bundles.

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Antimicrobial therapy should not be delayed while waiting for results of BAL samples. (Masterton et al., 2008) [Evidence level C]

The results of prior BAL and other microbiology samples should be taken into consideration when choosing empirical therapy [e.g. MRSA colonization]. [Evidence level D]

The empirical antimicrobial therapy of VAP is determined by the duration of time in hospital (Anon, 2005; Masterton et al., 2008). [Evidence level C]

A. Early onset VAP [≤4 days in hospital] AND not currently on antimicrobials AND <24 hours antimicrobial therapy in the last week.

1. Patients who do NOT have severe sepsis or septic shock
Co-amoxiclav  1.2g 8-hourly iv, add Clarithromycin 500mg 12-hourly iv if strong clinical suspicion of Legionella infection (Anon, 2005; Masterton et al., 2008). [Evidence level C].

Substitute Cefuroxime 1.5g 8-hourly iv for Co-amoxiclav in a patient with a penicillin allergy which is non-severe and/or if cephalosporins have been tolerated previously and if <65 years old. [Evidence level C].

Substitute Levofloxacin 500mg 12-hourly iv in a patient with severe penicillin allergy or >65years old (Anon, 2005) [Evidence level C] [N.B. Clarithromycin will not be required in this situation.]

2. Patients who have severe sepsis or septic shock
Meropenem  1g 8-hourly iv, add Clarithromycin 500mg 12-hourly iv if strong clinical suspicion of Legionella infection. [Evidence level D].

Substitute Levofloxacin 500mg 12-hourly iv in a patient with severe penicillin allergy [Evidence level D].

B. Early onset VAP [≤4 days in hospital] and on antimicrobials or >24 hours antimicrobial therapy in the last week.

1. Patients who do not have severe sepsis or septic shock
Piperacillin/tazobactam  4.5g 6-hourly iv, add Clarithromycin 500mg 12-hourly iv if strong clinical suspicion of Legionella infection. [Evidence level D].
Recent Piperacillin/tazobactam or non severe penicillin allergy substitute with Meropenem 1g 8-hourly iv. [Evidence level D].

2. Patients who have severe sepsis or septic shock
Meropenem  1g 8-hourly iv, add Clarithromycin 500mg 12-hourly iv if strong clinical suspicion of Legionella infection. [Evidence level D].

Substitute Levofloxacin 500mg 12-hourly iv in a patient with severe penicillin allergy [Evidence level D].

C. Late onset VAP [≥5 days in hospital]

1. Patients who do not have severe sepsis or septic shock
Piperacillin/tazobactam  4.5g 8-hourly iv, add Clarithromycin 500mg 12-hourly iv if strong clinical suspicion of Legionella infection. [Evidence level D].

[N.B. Recent Piperacillin/tazobactam or non severe penicillin allergy substitute with Meropenem 1g 8-hourly iv. [Evidence level D].]

2. Patients who have severe sepsis or septic shock
Meropenem 1g 8-hourly iv, add Clarithromycin 500mg 12-hourly iv if strong clinical suspicion of Legionella infection. [Evidence level D].

Substitute Linezolid ^# 600mg 12-hourly PO/IV plus Ciprofloxacin 400mg 12-hourly iv in a patient with severe penicillin allergy, if recent Ciprofloxacin discuss with microbiology. [Evidence level D].

MRSA
If a patient has risk factors for MRSA [see box] consider adding Linezolid ^# to any empirical regimen that does not already include Linezolid ^#. Evidence level D

^#Linezolid has a number of drug interactions/contraindications. Please see full guidance to check suitability for the patient.

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Empirical antimicrobial therapy should be reviewed daily with microbiology results and converted to directed therapy wherever possible [Evidence level C].

If no pathogen[s] have been isolated consider if antimicrobial[s] are still indicated. [Evidence level C]

If  Linezolid ^# is being used due to identified MRSA risk consider stopping if S. aureus is not isolated and/or another significant pathogen been isolated. [Evidence level C].

Table 1. Directed antimicrobial regimens for VAP.

*review doses with renal function.

#Linezolid has a number of drug interactions/contraindications. Please see full guidance to check suitability for the patient.

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With the exception of infection caused by Pseudomonas aeruginosa, VAP can be treated with 7 days of appropriate antimicrobials, provided there has been a good clinical response (Anon, 2005; Masterton et al., 2008). [Evidence level A]

VAP caused by Pseudomonas aeruginosa can be treated with 10-14 days of appropriate antimicrobial monotherapy, provided there has been a good clinical response. [Evidence level D]

If aminoglycosides are used to supplement beta-lactam antibiotics for treatment of Pseudomonas aeruginosa VAP then short course aminoglycoside therapy [≤5 days] should be considered.

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There are no data to guide the switch to oral antimicrobial therapy for VAP, but agents with good oral bioavailability such as Ciprofloxacin or Linezolid ^# can be considered in patients who are adequately absorbing from the gastrointestinal tract. Other cases should be assessed on the basis of clinical response and the availability of appropriate agents.

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