Cefepime's Adequacy for Treating Infections
Cefepime is an adequate first-line antibiotic for treating various infections, particularly as monotherapy for high-risk febrile neutropenia, moderate to severe pneumonia, and complicated intra-abdominal infections (when combined with metronidazole), but it should be used with caution for ESBL-producing organisms where carbapenems are preferred. 1, 2
Spectrum of Activity and FDA Indications
Cefepime is a fourth-generation cephalosporin with broad-spectrum activity against both gram-positive and gram-negative bacteria. According to the FDA label, cefepime is indicated for:
- Pneumonia (moderate to severe)
- Empiric therapy for febrile neutropenic patients
- Uncomplicated and complicated urinary tract infections
- Uncomplicated skin and skin structure infections
- Complicated intra-abdominal infections (in combination with metronidazole) 2
Its antimicrobial activity includes coverage against:
- Gram-negative bacteria: Enterobacter species, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa
- Gram-positive bacteria: Methicillin-susceptible Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes, and viridans group streptococci 2
Specific Clinical Applications
Febrile Neutropenia
Cefepime is highly recommended as monotherapy for high-risk patients with febrile neutropenia. The Infectious Diseases Society of America (IDSA) guidelines specifically state that "monotherapy with an anti-pseudomonal β-lactam agent, such as cefepime, a carbapenem, or piperacillin-tazobactam are each as effective as multidrug combinations and are recommended as first-line therapy" 1. This recommendation is based on multiple clinical trials showing equivalent efficacy to other regimens with fewer adverse events.
Pneumonia
For moderate to severe pneumonia, cefepime at 1-2g IV every 8-12 hours for 10 days is an appropriate treatment option. For Pseudomonas aeruginosa pneumonia specifically, a higher dose of 2g IV every 8 hours is recommended 3, 2.
Intra-abdominal Infections
For complicated intra-abdominal infections, cefepime 2g IV every 8-12 hours in combination with metronidazole for 7-10 days is recommended 2. In diabetic foot infections, cefepime can be part of a combination therapy for severe infections involving MRSA, Enterobacteriaceae, Pseudomonas, and obligate anaerobes 1.
Limitations and Considerations
ESBL-Producing Organisms
Caution is warranted when using cefepime for ESBL-producing Enterobacteriaceae. The European Society of Clinical Microbiology and Infectious Diseases (ESCMID) guidelines note inconsistent results with cefepime for these infections, with some studies showing higher mortality with cefepime, particularly when MICs are in the susceptible dose-dependent range 1.
Resistance Concerns
In settings with high incidence of ESBL-producing Enterobacteriaceae, extended use of cephalosporins including cefepime should be discouraged and limited to pathogen-directed therapy due to selective pressure resulting in emergence of resistance 1.
Dosing Considerations
Dosing should be adjusted based on:
- Renal function: Dose reduction is necessary when creatinine clearance is ≤60 mL/min 2
- Infection severity: Higher doses (2g every 8 hours) are recommended for severe infections and Pseudomonas infections 2
- Patient age: Elderly patients may require dose adjustments based on renal function 2
Safety Profile
Cefepime has a safety profile similar to other parenteral cephalosporins. Common adverse reactions (≥1%) include:
- Local reactions
- Positive Coombs' test
- Decreased phosphorous
- Increased ALT and AST
- Increased PT and PTT
- Rash 2
At higher doses (2g every 8 hours), additional adverse reactions include diarrhea, nausea, vomiting, pruritus, fever, and headache 2.
Conclusion
Cefepime remains a reliable first-line agent for empirical antibiotic coverage for various infections, particularly for febrile neutropenia. While concerns were raised about increased mortality with cefepime use in a meta-analysis by Yahav et al., subsequent FDA analysis found no statistically significant increase in 30-day mortality associated with cefepime use 1. Therefore, cefepime continues to be considered an adequate and effective antibiotic option for treating serious bacterial infections when used appropriately based on local resistance patterns and patient-specific factors.