IDSA/ATS: Infectious Diseases Society of America/American Thoracic Society; HAP: hospital-acquired pneumonia; VAP: ventilator-associated pneumonia; ICU: intensive care unit; MDR: multidrug-resistant; IV: intravenous; ARDS: acute respiratory distress syndrome; MRSA: methicillin-resistant Staphylococcus aureus.
* Among these agents, we generally prefer piperacillin-tazobactam or cefepime because they are more likely to have activity against gram-negative bacilli than levofloxacin. 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 Among these agents, we generally prefer piperacillin-tazobactam, cefepime, or ceftazidime because they are more likely to have activity against gram-negative bacilli than the fluoroquinolones or aztreonam. 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 ESBL-producing gram-negative bacilli.
◊ The combination of vancomycin and piperacillin-tazobactam has been associated with acute kidney injury. In patients who require an anti-MRSA agent and an antipseudomonal beta-lactam, options include using a beta-lactam other than piperacillin-tazobactam (eg, cefepime or ceftazidime) or, if piperacillin-tazobactam is favored, using linezolid instead of vancomycin.
§ Telavancin (10 mg/kg IV every 24 hours) is an alternative agent when neither linezolid nor vancomycin can be used, but there are several boxed warnings that must be considered before choosing it. Boxed warnings include information about risk of acute kidney injury, increased mortality in patients with pre-existing acute kidney failure, and concerns about safety in fetuses when used during pregnancy. Refer to the UpToDate topic review on treatment of HAP and VAP for additional details.
¥ The vancomycin loading dose is based on actual body weight; the dose is rounded to the nearest 250 mg increment and not exceeding 3000 mg. Within this range, we use a higher dose for critically ill patients.
‡ Refer to the UpToDate topic on vancomycin dosing for sample nomogram.
† Refer to the UpToDate topic on vancomycin dosing for discussion of AUC-guided and trough-guided vancomycin dosing.
** Ceftazidime-avibactam, ceftolozane-tazobactam, and imipenem-cilistatin-relebactam are potential single-agent alternatives for patients at risk for infection with MDR gram-negative pathogens.
¶¶ 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 not concern for Legionella, as aminoglycosides are more likely to have in vitro activity against gram-negative bacilli in those with risk factors for resistance. In contrast, the guidelines state that aminoglycosides should be avoided if alternative agents with adequate gram-negative activity are available.
ΔΔ The IDSA/ATS guidelines include the polymyxins (polymyxin B and colistin) as options for the second agent for gram-negative bacilli. Polymyxins are used rarely given their significant nephrotoxicity and should be avoided if alternative agents with adequate activity against gram-negative bacilli are available. When they are required, an infectious disease physician and/or pharmacist with expertise using these agents should be consulted.
◊◊ Monitoring drug concentrations and adjustment of doses and/or intervals are required. Refer to the UpToDate topic reviews and tables on dosing of aminoglycosides for details about the approach to initial dosing (including the appropriate body weight to use in dosing calculations, kidney function assessment, and monitoring).
§§ We typically discontinue the aminoglycoside after one or two days, especially in patients who have improved clinically and in whom the pathogen (if identified) is susceptible to the beta-lactam.
¥¥ In the absence of other options, it is acceptable to use aztreonam as a second agent for gram-negative bacilli with another beta-lactam because it has different targets within the bacterial cell wall.
‡‡ We use aztreonam infrequently since rates of resistance among gram-negative bacilli are typically higher than to the other beta-lactams options.