Is cefepime (Cefepime) effective against gram-positive cocci, including methicillin-resistant Staphylococcus aureus (MRSA) and Streptococcus pneumoniae?

Does Cefepime Cover Gram-Positive Cocci?

Yes, cefepime provides good coverage against many gram-positive cocci, including methicillin-susceptible Staphylococcus aureus (MSSA) and Streptococcus pneumoniae (including penicillin-resistant strains), but it does NOT cover methicillin-resistant Staphylococcus aureus (MRSA) or enterococci. 1, 2

Spectrum of Activity Against Gram-Positive Cocci

Organisms Covered by Cefepime

• Methicillin-susceptible Staphylococcus aureus (MSSA): Cefepime demonstrates good activity against MSSA, with in vitro activity comparable to cefotaxime and ceftriaxone 1, 3, 2
• Coagulase-negative staphylococci (methicillin-susceptible only): Cefepime is active against methicillin-susceptible strains of S. epidermidis and S. saprophyticus 1, 4
• Streptococcus pneumoniae: Cefepime maintains excellent activity against penicillin-susceptible, penicillin-intermediate, and penicillin-resistant strains of S. pneumoniae 5, 1, 3, 2
• Streptococcus pyogenes (Group A Streptococcus): Cefepime is highly active against this pathogen 1, 4, 2
• Viridans group streptococci: These organisms are susceptible to cefepime 1, 4
• Streptococcus agalactiae (Group B Streptococcus): Cefepime demonstrates activity against this organism 1

Organisms NOT Covered by Cefepime

• Methicillin-resistant Staphylococcus aureus (MRSA): Cefepime has poor activity against MRSA and should never be used as monotherapy for documented or suspected MRSA infections 1, 4, 6
• Methicillin-resistant coagulase-negative staphylococci: These organisms are resistant to cefepime 1, 4
• Enterococci (Enterococcus faecalis and other species): Cefepime is inactive against enterococci 1, 6

Clinical Context: When Cefepime's Gram-Positive Coverage Is Appropriate

Community-Acquired Pneumonia (CAP)

• For hospitalized patients with CAP, cefepime is NOT a first-line agent—guidelines recommend ceftriaxone, cefotaxime, or ampicillin-sulbactam as preferred β-lactams 5, 7
• Cefepime should be reserved for patients with specific risk factors for Pseudomonas aeruginosa, such as structural lung disease, recent hospitalization with IV antibiotics, or prior P. aeruginosa isolation 7, 8
• When used for CAP with pseudomonal risk factors, cefepime must be combined with either a macrolide (azithromycin) or respiratory fluoroquinolone to cover atypical pathogens 7, 8

Febrile Neutropenia

• Cefepime is an acceptable first-line monotherapy agent for high-risk febrile neutropenic patients, providing coverage for both gram-negative organisms (including P. aeruginosa) and gram-positive cocci like MSSA and streptococci 5
• However, vancomycin should be added empirically if the patient has specific risk factors for MRSA or gram-positive resistant organisms 5

Hospital-Acquired/Ventilator-Associated Pneumonia

• Cefepime is appropriate as an antipseudomonal β-lactam in combination regimens for hospital-acquired pneumonia (HAP) or ventilator-associated pneumonia (VAP) 8
• For suspected MRSA (based on positive MRSA PCR, prior MRSA infection, or high local prevalence), vancomycin or linezolid must be added to cefepime 8

Critical Pitfalls to Avoid

• Never use cefepime as monotherapy for documented or suspected MRSA infections—it has no clinically useful activity against methicillin-resistant staphylococci 1, 4
• Do not use cefepime for enterococcal infections—these organisms are uniformly resistant 1, 6
• For MSSA bacteremia, de-escalate from cefepime to cefazolin, nafcillin, or oxacillin once susceptibility is confirmed—cefepime represents suboptimal definitive therapy for MSSA compared to narrower-spectrum agents 9
• Cefepime is inferior to ceftriaxone/cefotaxime for routine CAP—reserve cefepime for patients with documented pseudomonal risk factors 5, 7
• Always add MRSA coverage (vancomycin or linezolid) when risk factors are present, such as prior MRSA colonization, recent hospitalization with IV antibiotics, post-influenza pneumonia, or cavitary infiltrates 8

Comparative Activity: Cefepime vs. Other Cephalosporins for Gram-Positive Cocci

• Cefepime vs. ceftriaxone/cefotaxime: Comparable activity against S. pneumoniae (including penicillin-resistant strains) and MSSA, but ceftriaxone/cefotaxime are preferred for CAP due to more extensive clinical data 5, 3
• Cefepime vs. ceftazidime: Cefepime has superior gram-positive activity compared to ceftazidime, which has poor activity against streptococci and should not be used for pneumonia 5, 3
• Cefepime vs. cefazolin: Cefazolin is the preferred agent for MSSA bacteremia due to superior pharmacodynamic profile; cefepime should be de-escalated to cefazolin once MSSA is confirmed 9