Empiric treatment of ventilator-associated pneumonia (VAP) in adults with normal kidney function

ARDS: acute respiratory distress syndrome; HAP: hospital-acquired pneumonia; ICU: intensive care unit; IDSA/ATS: Infectious Diseases Society of America/American Thoracic Society; IV: intravenous; MDR: multidrug-resistant; MRSA: methicillin-resistant Staphylococcus aureus; VAP: ventilator-associated pneumonia.

* We generally prefer piperacillin-tazobactam or cefepime because they are more likely to have activity against gram-negative bacilli than levofloxacin. However, levofloxacin 750 mg IV daily may be preferred if there is a high suspicion for Legionella spp infection and local resistance rates of S. aureus, P. aeruginosa, and other gram-negative bacilli to fluoroquinolones are low. The IDSA/ATS guidelines also include imipenem and meropenem as options, but we generally reserve these agents for patients with a high likelihood of infection with extended-spectrum beta-lactamase (ESBL)-producing gram-negative bacilli.

¶ We favor prolonged infusions of broad-spectrum beta-lactams for empiric and targeted therapy of gram-negative bacilli in critically ill patients as well as in patients with infections caused by gram-negative bacilli that have elevated but susceptible minimum inhibitory concentrations to the chosen agent. Refer to the related UpToDate table and topic review on prolonged infusions of beta-lactams for dosing information. The dosing information provided above represents traditional intermittent dosing (eg, administered over 30 minutes).

Δ Vancomycin and anti-pseudomonal beta-lactams, particularly piperacillin-tazobactam, have been associated with acute kidney injury, although the risk is uncertain. Patients receiving vancomycin with piperacillin-tazobactam should be closely monitored for renal dysfunction or alternative antibiotic combinations should be used.

◊ If none of the mentioned beta-lactam beta-lactamase agents are available, combination therapy of a carbapenem (eg, meropenem, imipenem-cilastatin) WITH another anti-gram negative agent (eg, aminoglycosides, anti-pseudomonal fluoroquinolone, polymyxin/colistin, or aztreonam) is an appropriate alternative. The IDSA/ATS guidelines recommend either an antipseudomonal fluoroquinolone or an aminoglycoside for the second agent for gram-negative bacilli, but we generally prefer an aminoglycoside over a fluoroquinolone if there is no concern for Legionella, as aminoglycosides are more likely to have in vitro activity against gram-negative bacilli in those with risk factors for resistance. Monitoring drug concentrations and adjustment of doses and/or intervals are required. Refer to the UpToDate topic reviews and tables on dosing and precautions prior to initiating combination therapy. When any of these alternative agents are required, an infectious disease physician and/or pharmacist with expertise using these agents should be consulted.