Pneumonia, Ventilator-Associated
Empiric therapy: ventilator-associated pneumonia (VAP)
Clinical Setting
- Empiric therapy for ventilator-associated pneumonia.
- Pneumonia develops ≥ 48 hours of mechanical ventilation.
- Diagnostic criteria for VAP:
- Clinical suspicion and presence of new or progressive pulmonary infiltrates on chest radiograph PLUS two of the following:
- Fever
- Peripheral leukocytosis
- Purulent tracheal secretions
- Proposed surveillance diagnostic criteria: Clin Infect Dis 57:1742, 2013.
- Culture, gram strain of tracheal aspirate or lavage fluid should be performed in all cases of suspected VAP.
- Differential diagnosis includes:
- Nonbacterial pathogens
- Fever due to ischemia, malignancy, drug-induced pneumonia
- Infiltrates due to congestive heart failure
- For full list: Scand J Infect Dis 46:868, 2014.
- 2016 IDSA Guidelines: Clin Infect Dis 63:e61, 2016 (full article); executive summary: Clin Infect Dis 63:575, 2016.
- For prophylaxis, see comments
Etiologies
- Early-onset (<5 days in the hospital, no other risk factors for multi-drug resistant (MDR) organisms)
- Strep. pneumoniae
- H. influenzae
- Enteric gram-negative bacilli
- Late-onset (≥ 5 days in the hospital, risk factors of MDR organisms present)
- Staph. aureus (often methicillin-resistant (MRSA))
- Gram-negative enterics (often multidrug resistant)
- E. coli
- Klebsiella pneumoniae
- Enterobacter sp.
- Serratia marcescens
- Pseudomonas aeruginosa
- Acinetobacter baumannii
- In literature review, ESKAPE pathogens etiologic in 80% of patients: Curr Opin Pulm Med 20:252, 2014.
Primary Regimens
- Low risk of MRSA (ICU prevalence <10-20%), no risk factors for MDR pathogens,
- Cefepime 2 gm IV q8h
- Piperacillin-tazobactam 4.5 gm IV q6h (not recommended if ESBL-producing organism is suspected)
- Meropenem 1 gm IV q8h
- Levofloxacin 750 mg IV/po q24h (not recommended if ESBL-producing organism is suspected)
- More severe disease, i.e., sepsis, hypotension, rapid progression of infiltrates on chest radiograph indicating high risk of mortality; MDR risk factor, MRSA prevalence >10-20%
- Vancomycin 15-20 mg/kg IV q8-12h + (Cefepime 2 gm IV q8h or Piperacillin-tazobactam 4.5 gm q6h or Meropenem 1 gm q8h)
- If Legionella suspected, add Levofloxacin 750 mg po/IV q24h or Azithromycin 500 mg IV q24h to the regimen.
- To increase likelihood that at least one drug will be active, if Pseudomonas or MDR Gram-negative suspected, add:
- Ciprofloxacin 400 mg IV q8h or Levofloxacin 750 mg IV q24h or Tobramycin 5-7 mg/kg IV q24h or Amikacin 15-20 mg/kg IV q24h
- Duration of therapy: See Antimicrobial Stewardship
Alternative Regimen
- Linezolid 600 mg IV q12h can be substituted for Vancomycin
- Substitute Ceftazidime-avibactam 2.5 gm IV infused over 2 hours q 8h for Cefepime, Piperacillin-tazobactam or Meropenem if carbapenem-resistant enterobacteriaceae is suspected
- Aztreonam 2 gm IV q8h instead of cefepime, piperacilli-tazobactam, or meropenem for patients with severe IgE-mediated hypersensitivity to beta-lactams. However, unlike these other agents, aztreonam is not active against S. aureus or S.pneumoniae and hence should add vancomycin pending culture results.
- Ceftolozane-tazobactam 3 g IV q8h covers pseudomonas and ESBL-producing Enterobacteriaceae (Lancet Infect Dis 2019 Dec;19(12):1299-1311).
Antimicrobial Stewardship
- If S. aureus nares screen is negative for MRSA no need to empirically cover for MRSA, and if coverage initiated, de-escalation is safe with a negative predictive value of 96.1% (Clin Infect Dis 2019 Oct 1. pii: ciz974. doi: 10.1093/cid/ciz974).
- Duration of therapy is not well defined.
- For relatively susceptible pathogens treat for 8 days.
- For Staph. aureus, MRSA in particular, or more resistant organisms (e.g., Pseudomonas, Acinetobacter, Stenotrophomonas) treat for longer, e.g., 14 days.
- Alternatively, can trend serum procalcitonin levels
- Retrospective cohort study found that 1-3 days of therapy was as effective as > 3 days for patients with suspected VAP and minimal and stable ventilator settings defined as daily minimum PEEP of ≤5 cm H2O and daily minimum FiO2 <40% for at least 3 days from the first day of antibiotics (Clin Infect Dis 64:870, 2017).
Comments
- If MDR pathogens are suspected, initial coverage should be broad and then streamlined based on culture and susceptibility results.
- Risk factors for MDR organisms:
- Antimicrobial therapy in preceding 90 days.
- Current hospitalization of 5 days or more.
- Septic shock at time of VAP
- Acute renal replacement therapy prior to onset of VAP
- Antibiotic resistance prevalent in the community or specific hospital unit
- Empiric regimen of choice may vary based on local prevalence and susceptibility of pathogens, known prior colonization with MDR organisms, prior treatment history, severity of illness.
- Prevention/prophylaxis of VAP (Am J Infect Control 42:34, 2014):
- Elevate head of bed by 30º or more.
- Remove NG endotracheal tubes as soon as possible.
- Continuous subglottic suctioning (Crit Care Med 43:22, 2015; Crit Care Med 43:227, 2015).
- Chlorhexidine oral care.
- Silver-coated endotracheal tubes may reduce incidence of VAP: JAMA 300:805, 2008; JAMA 300:842, 2008.
- Prevention of VAP in patients with post cardiac arrest and targeted hypothermia management (N Engl J Med. 2019; 381:1831-1842).
- Multicenter, double-blind, randomized , placebo-controlled trial in adults (where available)
- VAP in first 7 days: Placebo: 34%; Amoxicillin-clavulanatae 19 %, p 0.03
- Multicenter, double-blind, randomized , placebo-controlled trial in adults (where available)
- 2017 European Guidelines: (Eur Respir J 2017; 50: 1700582)