Ventilator-associated pneumonia - Guideline for the Management of

Publication: 01/01/2009  
Last review: 19/09/2017  
Next review: 02/02/2020  
Clinical Guideline
CURRENT 
ID: 1544 
Approved By: Improving Antimicrobial Prescribing Group 
Copyright© Leeds Teaching Hospitals NHS Trust 2017  

 

This Clinical Guideline is intended for use by healthcare professionals within Leeds unless otherwise stated.
For healthcare professionals in other trusts, please ensure that you consult relevant local and national guidance.

Guideline for management of ventilator-associated pneumonia

  • Treatment Algorithm
  • Summary
    Ventilator-associated pneumonia

    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 38oC or hypothermia <36oC
    • 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

    Back to top

    Background

    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.

    Back to top

    Clinical Diagnosis

    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 38oC
    • 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)]

    Back to top

    Investigation

    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]

    Back to top

    Treatment
    Non-Antimicrobial Treatment

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

    Back to top

    Empirical Antimicrobial Treatment

    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 electronic Medicines Compendium information on Co-amoxiclav 1.2g 8-hourly iv, add Clarithromycin electronic Medicines Compendium information on Clarithromycin 500mg 12-hourly iv if strong clinical suspicion of Legionella infection (Anon, 2005; Masterton et al., 2008). [Evidence level C].

    Substitute Cefuroxime electronic Medicines Compendium information on Cefuroxime 1.5g 8-hourly iv for Co-amoxiclav electronic Medicines Compendium information on Co-amoxiclavin 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 electronic Medicines Compendium information on Levofloxacin 500mg 12-hourly iv in a patient with severe penicillin allergy or >65years old (Anon, 2005) [Evidence level C] [N.B. Clarithromycin electronic Medicines Compendium information on Clarithromycin will not be required in this situation.]

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

    Substitute Levofloxacin electronic Medicines Compendium information on 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 electronic Medicines Compendium information on Piperacillin/tazobactam 4.5g 8-hourly iv, add Clarithromycin electronic Medicines Compendium information on Clarithromycin 500mg 12-hourly iv if strong clinical suspicion of Legionella infection. [Evidence level D].
    Recent Piperacillin/tazobactam electronic Medicines Compendium information on Piperacillin/tazobactam or non severe penicillin allergy substitute with Meropenem electronic Medicines Compendium information on Meropenem 1g 8-hourly iv. [Evidence level D].

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

    Substitute Levofloxacin electronic Medicines Compendium information on 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 electronic Medicines Compendium information on Piperacillin/tazobactam 4.5g 8-hourly iv, add Clarithromycin electronic Medicines Compendium information on Clarithromycin 500mg 12-hourly iv if strong clinical suspicion of Legionella infection. [Evidence level D].

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

    2. Patients who have severe sepsis or septic shock
    Meropenem electronic Medicines Compendium information on Meropenem1g 8-hourly iv, add Clarithromycin electronic Medicines Compendium information on Clarithromycin 500mg 12-hourly iv if strong clinical suspicion of Legionella infection. [Evidence level D].

    Substitute Linezolid electronic Medicines Compendium information on 

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

    MRSA
    If a patient has risk factors for MRSA [see box] consider adding Linezolid electronic Medicines Compendium information on 

Linezolid# to any empirical regimen that does not already include Linezolid electronic Medicines Compendium information on 

Linezolid #. Evidence level D

    #Linezolid electronic Medicines Compendium information on 

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

    Risk factors for MRSA

    1. Known MRSA positive patient [any specimen site] [Evidence level C]
    2. Recent [within past 2 weeks] quinolone [e.g. Ciprofloxacin electronic Medicines Compendium information on CiprofloxacinLevofloxacin electronic Medicines Compendium information on Levofloxacin or moxifloxacin] [Evidence level D].
    3. BAL direct microscopy result: neutrophils present, Gram positive cocci ++/+++ alone in patient ≥ 4 days in hospital or transferred from another health care facility [Evidence level D].

    Back to top

    Directed Antimicrobial Treatment (when microbiology results are known)

    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 electronic Medicines Compendium information on 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.

     

    No known penicillin allergy

    Non-severe penicillin allergy

    severe penicillin allergy

    Staphylococcus aureus meticillin susceptible

    Flucloxacillin electronic Medicines Compendium information on Flucloxacillin * 1-2g 6-hourly iv

    Cefuroxime electronic Medicines Compendium information on Cefuroxime * 1.5g 8-hourly iv
    >65 years use allergy regimen

    Linezolid electronic Medicines Compendium information on Linezolid #600mg 12-hourly iv/po

    Staphylococcus aureus meticillin resistant

    Linezolid electronic Medicines Compendium information on Linezolid #600mg 12-hourly iv/po

    Linezolid electronic Medicines Compendium information on Linezolid #600mg 12-hourly iv/po

    Linezolid electronic Medicines Compendium information on Linezolid #600mg 12-hourly iv/po

    Enterobacteriaceae [“coliforms”]

         

    Amoxicillin electronic Medicines Compendium susceptible

    Amoxicillin electronic Medicines Compendium* 1g 6-h iv

    Cefuroxime electronic Medicines Compendium information on Cefuroxime* 1.5g 8-h iv
    >65 years use allergy regimen

    Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin* 400mg 12-h iv or Aztreonam electronic Medicines Compendium* 1g 8-h iv

    Amoxicillin electronic Medicines Compendium resistant cephalosporin susceptible

    Cefuroxime electronic Medicines Compendium information on Cefuroxime* 1.5g 8-h iv
    >65 years use allergy regimen

    Cefuroxime electronic Medicines Compendium information on Cefuroxime* 1.5g 8-h iv
    >65 years use allergy regimen

    Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin* 400mg 12-h iv or Aztreonam electronic Medicines Compendium* 1g 8-h iv

    Amoxicillin electronic Medicines Compendium, cephalosporin resistant [inc ESBL]

    Piperacillin/tazobactam electronic Medicines Compendium information on Piperacillin/tazobactam* 4.5g 8-h iv*, Meropenem electronic Medicines Compendium information on Meropenem* 1g 8-h iv, ertapenem* 1g 24-h iv, Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin* 400mg 12-h iv depending on susceptibility

    Meropenem electronic Medicines Compendium information on Meropenem* 1g 8-h iv, ertapenem* 1g 24-h iv, Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin*400mg 12-h iv depending on susceptibility

    Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin*400mg 12-h iv or colistin* 1-2Mu 8-h iv or Tigecycline electronic Medicines Compendium 100mg loading then 50mg 12-h iv, depending on susceptibility

    Pseudomonas aeruginosa

    Piperacillin/tazobactam electronic Medicines Compendium information on Piperacillin/tazobactam* 4.5g 8-h iv*, Meropenem electronic Medicines Compendium information on Meropenem* 1g 8-h iv, Ceftazidime electronic Medicines Compendium information on Ceftazidime* 2g 8-h iv, Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin* 400mg 12-h iv depending on susceptibility

    Meropenem electronic Medicines Compendium information on Meropenem* 1g 8-h iv, Ceftazidime electronic Medicines Compendium information on Ceftazidime* 2g 8-h iv, Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin* 400mg 12-h iv depending on susceptibility

    Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin* 400mg 12-h iv or Gentamicin* 7mg/kg iv depending on susceptibility

    Acinetobacter spp.

    Case-by-case according to susceptibility

    Case-by-case according to susceptibility

    Case-by-case according to susceptibility

    Others

    Case-by-case according to susceptibility

    Case-by-case according to susceptibility

    Case-by-case according to susceptibility

    *review doses with renal function.

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

    Back to top

    Duration of Treatment

    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.

    Antibiotic [including “Penicillin”] Allergies:

    • The nature of all reported antimicrobial allergies, particularly to penicillins or other β lactams, should be clarified as far as practicable. It should also be determined if possible which antimicrobials [in particular of same or related classes] the patient has previously received without any reported adverse effects.
      • Features suggestive of genuine drug allergy
        • Severe, including
          1. Immediate Hypersensitivity [“Type I”] reactions: Anaphylaxis, difficulty breathing / bronchospasm, urticaria, hypotension, lip or other facial swelling / angioedema
          2. Idiopathic e.g. severe skin reactions, such as Stevens-Johnson syndrome, toxic epidermal necrolysis or widespread exfoliative dermatitis; seizures; loss of consciousness
        • Mild – Moderate:
          1. Other skin rashes: e.g. maculopapular [morbilliform].
          2. If patient / accompanying relatives unable to give a history of the specific features of the allergy & no other available record of nature of previous reaction[s]: treat as if mild-moderate [and monitor for any significant adverse effects post first dose of appropriate β-lactam in case of penicillin allergy].
      • Features suggestive of drug intolerance -
        Gastro-intestinal symptoms, e.g. nausea, vomiting, abdominal pain; and/or a feeling of faintness; during or following drug administration.

    Back to top

    Switch to oral agent(s)

    There are no data to guide the switch to oral antimicrobial therapy for VAP, but agents with good oral bioavailability such as Ciprofloxacin electronic Medicines Compendium information on Ciprofloxacin or Linezolid electronic Medicines Compendium information on 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.

    Back to top

    Treatment Algorithm

    Back to top

    Treatment Failure
    Please contact microbiology if the patient is not responding to the recommended antimicrobial regimens.

    Back to top

    Provenance

    Record: 1544
    Objective:
    • To provide evidence-based recommendations for appropriate investigation of ventilator-associated pneumonia.
    • To provide evidence-based recommendations for appropriate empirical or directed antimicrobial therapy of ventilator-associated pneumonia.
    • To recommend appropriate dose, route of administration and duration of antimicrobial agents.
    • To advise in the event of antimicrobial allergy.
    Clinical condition:

    Ventilator-associated pneumonia

    Target patient group: Adults
    Target professional group(s): Secondary Care Doctors
    Pharmacists
    Adapted from:

    Evidence base

    References
    Anon (2005). Guidelines for the management of adults with hospital-acquired, ventilator-associated, and healthcare-associated pneumonia. American journal of respiratory and critical care medicine 171, 388-416.

    Masterton, R. G., Galloway, A., French, G. & other authors (2008).Guidelines for the management of hospital-acquired pneumonia in the UK: Report of the Working Party on Hospital-Acquired Pneumonia of the British Society for Antimicrobial Chemotherapy, pp. 5-34.

    Evidence levels:
    A. Meta-analyses, randomised controlled trials/systematic reviews of RCTs
    B. Robust experimental or observational studies
    C. Expert consensus.
    D. Leeds consensus. [where no guidance exists or there is wide disagreement with a level C recommendation]

    Approved By

    Improving Antimicrobial Prescribing Group

    Document history

    LHP version 1.0

    Related information

    Not supplied

    Equity and Diversity

    The Leeds Teaching Hospitals NHS Trust is committed to ensuring that the way that we provide services and the way we recruit and treat staff reflects individual needs, promotes equality and does not discriminate unfairly against any particular individual or group.