Cefepime Antimicrobial Coverage
Cefepime is a fourth-generation cephalosporin with broad-spectrum activity covering most gram-negative organisms including Pseudomonas aeruginosa, Enterobacteriaceae (E. coli, Klebsiella, Enterobacter, Proteus), and gram-positive organisms including Streptococcus pneumoniae and methicillin-susceptible Staphylococcus aureus, but it lacks anaerobic coverage and is ineffective against MRSA, Enterococcus, and Campylobacter. 1
Gram-Negative Coverage
Cefepime provides excellent coverage against:
- Pseudomonas aeruginosa - comparable activity to ceftazidime, making it suitable for nosocomial pneumonia and febrile neutropenia 1, 2
- Enterobacteriaceae family including:
Key advantage: Cefepime maintains activity against many Enterobacteriaceae that are resistant to third-generation cephalosporins due to its stability against chromosomally-mediated beta-lactamases and low affinity for AmpC beta-lactamases 2, 3. This makes it particularly valuable for derepressed mutants of Enterobacter species that resist ceftriaxone and ceftazidime 2.
Gram-Positive Coverage
Cefepime covers:
- Streptococcus pneumoniae (including penicillin-sensitive, -intermediate, and -resistant strains) - activity similar to cefotaxime and ceftriaxone 2
- Streptococcus pyogenes 1
- Viridans group streptococci 1
- Methicillin-susceptible Staphylococcus aureus (MSSA) only 1, 3
The American College of Clinical Pharmacy notes that cefepime has broader gram-positive activity than third-generation cephalosporins like ceftazidime, which has poor activity against gram-positive cocci 4.
Critical Coverage Gaps
Cefepime does NOT cover:
- Anaerobes (including Bacteroides fragilis) - requires combination with metronidazole for intra-abdominal infections 1, 5
- Methicillin-resistant Staphylococcus aureus (MRSA) 1, 5
- Enterococcus species (including E. faecalis) 3, 5
- Campylobacter species - the American College of Emergency Physicians advises against cefepime for Campylobacter infections, as this represents inappropriate antimicrobial selection that will likely result in treatment failure 6
- Clostridium difficile 5
Resistance Considerations
Important limitations regarding ESBL-producing organisms:
- While cefepime has some stability against extended-spectrum beta-lactamases (ESBLs), the unchanged susceptible breakpoint (≤8 μg/mL) fails to identify many ESBL-producing E. coli, K. pneumoniae, and K. oxytoca 7
- Clinical efficacy of cefepime for treating infections caused by ESBL-producing organisms with lower MICs remains unclear 7
- Cefepime may be hydrolyzed by some ESBLs, though to a lesser extent than third-generation cephalosporins 2
The combination cefepime-sulbactam extends coverage to include many ESBL-producing organisms, though it remains ineffective against KPC-producing carbapenemase organisms 4.
FDA-Approved Indications Reflecting Coverage
The FDA label specifies cefepime for 1:
- Pneumonia (moderate to severe) - covering S. pneumoniae, P. aeruginosa, K. pneumoniae, Enterobacter species
- Febrile neutropenia - as monotherapy covering P. aeruginosa and serious gram-negative pathogens
- Urinary tract infections - covering E. coli, K. pneumoniae, P. mirabilis
- Skin and skin structure infections - covering MSSA and S. pyogenes only
- Complicated intra-abdominal infections - requires combination with metronidazole for anaerobic coverage
Common Pitfalls to Avoid
- Never use cefepime alone for intra-abdominal infections - always add metronidazole for anaerobic coverage 1
- Do not use for suspected MRSA infections - cefepime only covers methicillin-susceptible strains 1
- Avoid for gastrointestinal pathogens like Campylobacter - use macrolides or fluoroquinolones instead 6
- Exercise caution with known ESBL producers - consider carbapenems as preferred agents despite in vitro susceptibility 7