Cefepime for Gram-Negative Rod Infections
Cefepime is an effective treatment for susceptible gram-negative rod infections, particularly indicated for complicated intra-abdominal infections (in combination with metronidazole), pneumonia, urinary tract infections, and as empiric therapy for febrile neutropenia. 1
Spectrum of Activity and Indications
- Cefepime is a fourth-generation cephalosporin with activity against many gram-negative bacteria including Escherichia coli, Klebsiella pneumoniae, Enterobacter species, and Pseudomonas aeruginosa 1
- FDA-approved indications for cefepime include pneumonia, empiric therapy for febrile neutropenia, uncomplicated and complicated urinary tract infections, and complicated intra-abdominal infections (used in combination with metronidazole) 1
- For intra-abdominal infections, cefepime (2g every 8-12 hours) must be used in combination with metronidazole for adequate anaerobic coverage 1
Dosing Recommendations
- For moderate to severe infections: 1-2g IV every 8-12 hours 1
- For complicated intra-abdominal infections: 2g IV every 8-12 hours (with metronidazole) for 7-10 days 1
- For empiric therapy in febrile neutropenia: 2g IV every 8 hours 1
- Dose adjustment is required for patients with renal impairment (CrCL ≤60 mL/min) 1
Effectiveness Against Specific Gram-Negative Pathogens
Enterobacteriaceae
- For Enterobacteriaceae infections, cefepime has shown efficacy comparable to ceftriaxone and ertapenem in treating community-acquired pneumonia 2
- For Klebsiella pneumoniae infections, ertapenem has shown equivalent efficacy to cefepime in treating pneumonia with Enterobacteriaceae infection 2
ESBL-Producing Organisms
- For ESBL-producing Enterobacteriaceae, carbapenems (imipenem or meropenem) are recommended as first-line therapy for severe infections and bacteremia 2
- Cefepime may be considered for definitive therapy of invasive infections caused by ESBL-producing E. coli and Klebsiella species only when the MIC is ≤2 mg/L, with higher doses considered for MICs in the 4-8 mg/L range 3
- Clinical outcomes with cefepime for ESBL infections are concerning when MICs are ≥8 μg/mL, with mortality rates of 56.3% reported in one study 4
Carbapenem-Resistant Organisms
- For carbapenem-resistant Enterobacteriaceae (CRE), newer agents like meropenem-vaborbactam or ceftazidime-avibactam are preferred over cefepime for severe infections 2
- For carbapenem-resistant Pseudomonas aeruginosa (CRPA), ceftolozane-tazobactam is suggested if active in vitro 2
Combination Therapy Considerations
- For complicated intra-abdominal infections, cefepime must be combined with metronidazole for anaerobic coverage 1, 2
- For Pseudomonas aeruginosa infections, two antipseudomonal antibiotics may be empirically used initially due to the risk of resistance to a single agent 2
- New combination products like cefepime-zidebactam and cefepime-enmetazobactam show promise against multidrug-resistant gram-negative bacteria, including some carbapenemase producers 5, 6
Antimicrobial Stewardship Considerations
- To preserve carbapenems, cefepime may be used as a carbapenem-sparing option for susceptible organisms 2
- The use of cephalosporins should be limited in settings with high incidence of ESBL-producing Enterobacteriaceae due to selection pressure resulting in emergence of resistance 2
- Obtaining microbiological cultures before initiating therapy is recommended to guide targeted treatment and allow for de-escalation when appropriate 2
Important Caveats and Pitfalls
- Cefepime breakpoints have been questioned, with clinical failures observed at MICs previously considered susceptible (8 μg/mL) 4
- For severe infections with ESBL-producing organisms, carbapenems remain the treatment of choice due to more reliable clinical outcomes 2
- Cefepime has poor activity against methicillin-resistant Staphylococcus aureus, enterococci, Burkholderia cepacia, and Stenotrophomonas maltophilia 7
- Neurotoxicity may occur with cefepime, especially in patients with renal impairment receiving unadjusted doses 1
By following these evidence-based recommendations and considering the specific pathogen, resistance patterns, and severity of infection, clinicians can optimize the use of cefepime for gram-negative rod infections while practicing good antimicrobial stewardship.