From the Guidelines
Cefepime does not reliably cover MRSA (Methicillin-resistant Staphylococcus aureus). Cefepime is a fourth-generation cephalosporin with excellent activity against many gram-negative bacteria, including Pseudomonas aeruginosa, and some gram-positive organisms, but it lacks consistent activity against MRSA. MRSA is resistant to beta-lactam antibiotics, including most cephalosporins, due to its altered penicillin-binding protein (PBP2a) that has low affinity for beta-lactams.
Key Points to Consider
- For MRSA infections, appropriate antibiotic choices include vancomycin, daptomycin, linezolid, or trimethoprim-sulfamethoxazole for less severe infections 1.
- If MRSA is suspected or confirmed in a serious infection, it's essential to use one of these MRSA-active agents rather than cefepime, which would likely be ineffective and could lead to treatment failure.
- The most recent and highest quality study suggests that linezolid is significantly more effective than vancomycin in clinical and microbiological cure rates for MRSA infections 1.
Recommended Treatment
- Vancomycin (15-20 mg/kg IV every 8-12 hours)
- Daptomycin (4-6 mg/kg IV daily)
- Linezolid (600 mg IV/PO twice daily)
- Trimethoprim-sulfamethoxazole (1-2 double-strength tablets twice daily) for less severe infections. It's crucial to note that cefepime is not recommended for the treatment of MRSA infections due to its lack of consistent activity against this pathogen, and the potential for treatment failure and increased morbidity and mortality 1.
From the FDA Drug Label
NOTE: Most isolates of enterococci, e.g., Enterococcus faecalis, and methicillin-resistant staphylococci are resistant to cefepime. The FDA drug label states that cefepime is inactive against methicillin-resistant staphylococci (MRSA).
- Key points:
- Cefepime does not cover MRSA.
- MRSA is resistant to cefepime. 2
From the Research
Cefepime Coverage Against MRSA
- Cefepime has broad-spectrum activity against gram-negative and gram-positive organisms, including MRSA 3.
- Studies have shown that cefepime in combination with other antimicrobials, such as vancomycin, linezolid, or quinupristin-dalfopristin, has an improved or enhanced effect against MRSA 3.
- The minimum inhibitory concentrations (MICs) of cefepime for MRSA isolates were 4 μg/mL, indicating that cefepime may not be effective against MRSA when used alone 3.
- However, combination therapy with cefepime and other antimicrobials, such as aminoglycosides, has been shown to be effective against MRSA 3, 4, 5.
Clinical Evidence
- A retrospective cohort study found that concomitant empiric cefepime improved MRSA bloodstream infection clearance and reduced microbiologic failure when used in combination with vancomycin 4, 5.
- Another study found that cefepime in combination with vancomycin was associated with faster bloodstream infection clearance and reduced incidence of bloodstream infection durations ≥7 days 4, 5.
- However, cefepime is not typically considered a first-line treatment for MRSA infections, and other antibiotics such as vancomycin, linezolid, and daptomycin are often preferred 6, 7.
Safety and Efficacy
- The safety and efficacy of cefepime in combination with other antimicrobials for the treatment of MRSA infections have been evaluated in several studies 3, 4, 5.
- These studies have found that cefepime in combination with other antimicrobials is generally safe and effective for the treatment of MRSA infections, but more research is needed to fully understand its role in the treatment of these infections.