Ventilator-associated Pneumonia

Background

• Ventilator-associated pneumonia (VAP) refers to pneumonia occurring > 48 hours after endotracheal intubation in mechanically ventilated patients.
• About 10%-20% of patients requiring mechanical ventilation develop VAP. The duration of intubation is the most reproducible risk factor for VAP.
• Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), and gram-negative rods are among the most common pathogens.
• Risk factors for multidrug-resistant organisms (MDRO) include:
  • IV antimicrobial therapy within previous 90 days
  • septic shock at time of VAP
  • acute respiratory distress syndrome (ARDS) preceding VAP
  • acute renal replacement preceding VAP
  • current hospitalization > 5 days
• VAP-attributable mortality is estimated at 13% but rates vary greatly among subgroups and appear to correlate with the length of an intensive care unit (ICU) stay.

Evaluation

• Suspect ventilator-associated pneumonia (VAP) in any intubated and ventilated patient (or ≤ 48 hours post extubation) with combination of:
  • a new or progressive and persistent radiographic abnormality (particularly with air bronchograms)
  • ≥ 1 of compatible findings including:
    • hypoxia necessitating increase in positive end-expiratory pressure (PEEP) by 3 cm H₂O or the fraction of inspired oxygen (FiO₂) by 20%
    • fever
    • leukocytosis
    • a purulent sputum or adequate sputum sample (minimal squamous cells, usually < 10 squamous cells) with Gram stain with evidence of white blood cells (polymorphonuclear leukocytes [PMNs]) and/or a respiratory pathogen on a quantitative culture
• Obtain a complete blood count (CBC) with differential, arterial oxygenation saturation, complete metabolic panel, lower respiratory tract samples for Gram stain and culture, and blood cultures in patients with suspected VAP.
• Consider additional imaging such as chest computed tomography (CT) if the patient does not respond to initial empiric therapy.

Management

• Start antibiotic therapy as soon as possible; delays in the receipt of appropriate therapy are associated with increased mortality.
• Select an empiric antibiotic regimen based on local epidemiology, the severity of illness, and patient risk factors for multidrug-resistant organisms.
• Empiric regimens should be designed to target Staphylococcus aureus, Pseudomonas aeruginosa, and other gram-negative bacteria, such as (Strong recommendation).
  • piperacillin-tazobactam 4.5 g IV every 6 hours
  • cefepime 2 g IV every 8 hours
  • levofloxacin 750 mg IV every 24 hours
  • a carbapenem such as imipenem 500 mg IV every 6 hours or meropenem 1 g IV every 8 hours
• For patients with risk of MRSA, include 1 of (Weak recommendation):
  • vancomycin 15 mg/kg IV every 8-12 hours (target trough level 15-20 mg/mL) and consider loading dose of 25-30 mg/kg IV once in patients with severe illness
  • linezolid 600 mg IV every 12 hours
• For patients with ≥ 1 risk factor for multidrug-resistant (MDR) pathogens, consider 2 antipseudomonal antibiotics from different classes (Weak recommendation), including
  • a beta-lactam, such as
    • piperacillin-tazobactam 4.5 g IV every 6 hours
    • ceftazidime 2 g IV every 8 hours
    • meropenem 1 g IV every 8 hours
  • aztreonam 2 g IV every 8 hours
  • a quinolone, such as ciprofloxacin 400 mg IV every 8 hours
  • an aminoglycoside, such as amikacin 15-20 mg/kg IV every 24 hours or tobramycin 5-7 mg/kg IV every 24 hours
• Definitive therapy should be tailored to the infecting pathogen, if one can be identified (Weak recommendation).
• The duration of therapy is 7 days for most patients. Consider using procalcitonin levels to help define the treatment course (benefit unknown when standard antimicrobial course < 7 days) (Weak recommendation).