Pneumonia, Ventilator-Associated

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.

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
• Do NOT use Doripenem (see Comment)
• Duration of therapy: See Comments

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.

Antimicrobial Stewardship

• De-escalate therapy to treat specific pathogen(s) based on results of culture and susceptibility tests.
  • Can discontinue MRSA coverage if no MRSA isolated from respiratory cultures, if obtained, or if nasal swab or throat cultures show no growth of MRSA, or if  NAAT negative for MRSA (Antimicrob Agents Chemother 57:1163, 2013).
  • 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
• Doripenem Drug Warning: in prospective randomized trial of doripenem vs. imipenem, mortality rate was higher (23 vs 17%) and cure rate lower in the doripenem patients.
• 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 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.
• 2017 European Guidelines: (Eur Respir J 2017; 50: 1700582)