Cefepime Coverage of Gram-Negative Bacilli
Yes, cefepime provides excellent coverage against most Gram-negative bacilli, including Pseudomonas aeruginosa, and is recommended as first-line monotherapy for serious infections requiring broad-spectrum Gram-negative coverage. 1, 2
Spectrum of Activity Against Gram-Negative Organisms
Cefepime demonstrates robust activity against the following Gram-negative bacilli:
Enterobacteriaceae
- Excellent activity against Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Enterobacter species, Citrobacter species, and Serratia marcescens 2, 3
- Maintains activity against 99.1% of Enterobacter species, including strains with stably derepressed AmpC beta-lactamases that are resistant to third-generation cephalosporins 4
- Active against many extended-spectrum beta-lactamase (ESBL)-producing strains, though carbapenems remain preferred for confirmed ESBL infections 5, 6
Non-Fermentative Gram-Negative Bacilli
- Pseudomonas aeruginosa: Cefepime has activity comparable to ceftazidime, with 77-90% susceptibility rates in contemporary surveillance studies 1, 7, 4
- Coverage of P. aeruginosa is a critical component of empiric therapy for high-risk infections, which has historically driven antibiotic selection in febrile neutropenia and hospital-acquired pneumonia 1
Other Gram-Negative Organisms
- Active against Haemophilus influenzae, Moraxella catarrhalis, Morganella morganii, and Providencia species 2, 3
- Limited or no activity against Stenotrophomonas maltophilia, Burkholderia cepacia, and many Acinetobacter species 2, 8
Mechanism and Resistance Profile
- Cefepime is highly stable against chromosomally-encoded AmpC beta-lactamases and is a poor inducer of these enzymes, making it superior to third-generation cephalosporins for organisms like Enterobacter 2, 7
- It has low affinity for most beta-lactamases and exhibits rapid penetration into Gram-negative bacterial cells 2
- While it may be hydrolyzed by some extended-spectrum beta-lactamases, this occurs to a lesser extent than with third-generation cephalosporins 7, 6
Clinical Applications for Gram-Negative Coverage
Febrile Neutropenia
- Cefepime monotherapy is recommended as first-line empirical therapy for high-risk febrile neutropenic patients, specifically because of its excellent Gram-negative coverage including P. aeruginosa 1
- Gram-negative bacteremias carry 18% mortality compared to 5% for Gram-positive infections in this population, making adequate Gram-negative coverage essential 1
Hospital-Acquired and Ventilator-Associated Pneumonia
- For patients at high risk for multidrug-resistant pathogens but not in septic shock, cefepime is recommended as monotherapy if local susceptibility data show >90% activity against Gram-negative pathogens 1
- For septic shock, cefepime should be combined with an aminoglycoside or fluoroquinolone for dual Gram-negative coverage 1
Intra-Abdominal Infections
- Cefepime (third- or fourth-generation cephalosporin) must be combined with metronidazole for high-severity community-acquired intra-abdominal infections due to lack of anaerobic coverage 1
Important Caveats
- Ceftazidime is no longer reliable for empirical monotherapy due to decreasing potency against Gram-negative organisms, making cefepime a preferred alternative 1
- A controversial meta-analysis suggested increased 30-day mortality with cefepime in neutropenic patients, though subsequent FDA analysis did not confirm this finding 1
- For confirmed ESBL-producing organisms, particularly with higher MICs, carbapenems may be preferred over cefepime despite in vitro susceptibility 5
- Cross-resistance between cefepime and carbapenems or fluoroquinolones is incomplete, allowing these agents to retain activity when cefepime resistance emerges 6, 4