Cefepime Coverage of Streptococcus Species
Cefepime provides reliable coverage for most Streptococcus species, including Streptococcus pneumoniae (even penicillin-resistant strains), Streptococcus pyogenes, and viridans group streptococci, making it an appropriate choice for streptococcal infections in adults without β-lactam allergy. 1, 2
Spectrum of Activity Against Streptococci
Cefepime demonstrates excellent activity against the clinically important Streptococcus species:
Streptococcus pneumoniae: Cefepime is FDA-approved for pneumonia caused by S. pneumoniae, including cases with concurrent bacteremia, and maintains activity regardless of penicillin susceptibility status 1. The drug shows in vitro activity against penicillin-sensitive, penicillin-intermediate, and penicillin-resistant S. pneumoniae similar to cefotaxime and ceftriaxone 3.
Streptococcus pyogenes (Group A Streptococcus): Cefepime is FDA-approved for uncomplicated skin and skin structure infections caused by S. pyogenes 1. In vitro studies demonstrate that cefepime's activity against streptococci is superior to other tested cephalosporins 4.
Viridans group streptococci: Cefepime is FDA-approved for complicated intra-abdominal infections caused by viridans group streptococci when used in combination with metronidazole 1. The drug shows excellent activity against methicillin-sensitive coagulase-negative staphylococci, S. pyogenes, viridans streptococci, and S. pneumoniae 2.
Clinical Context and Guideline Support
The IDSA guidelines for febrile neutropenia specifically note that ceftazidime has poor activity against many gram-positive pathogens such as streptococci, which is why cefepime is preferred 5. This distinction highlights cefepime's superior streptococcal coverage compared to some other third-generation cephalosporins.
For specific streptococcal infections:
Pneumococcal pneumonia: The IDSA guidelines from 2000 show that third-generation cephalosporins like cefotaxime provide >90% coverage of S. pneumoniae across all penicillin susceptibility categories 5. While cefepime is not specifically listed in these older pneumonia guidelines, its fourth-generation status and FDA approval for pneumococcal pneumonia indicate comparable or superior activity 1.
Endocarditis: The American Heart Association guidelines recommend third-generation cephalosporins (cefotaxime or ceftriaxone) for pneumococcal endocarditis, including penicillin-resistant strains 5. While cefepime is not specifically mentioned for endocarditis, its similar spectrum suggests potential utility in consultation with infectious disease specialists.
Important Caveats
Enterococcal species are resistant to cefepime, as they are to all cephalosporins 2, 4. This is a critical limitation when considering empiric therapy for infections where enterococci are possible pathogens (such as intra-abdominal infections, where metronidazole must be added for anaerobic coverage but vancomycin may be needed for enterococcal coverage) 1.
Methicillin-resistant staphylococci are not reliably covered by cefepime 2, 4. While some methicillin-resistant strains may show susceptibility, this should not be relied upon for empiric therapy 6.
Practical Application
For empiric therapy where streptococcal coverage is needed:
Cefepime 2g IV every 8-12 hours provides reliable streptococcal coverage while also covering gram-negative organisms including Pseudomonas aeruginosa 1, 3.
In febrile neutropenia, where both gram-positive (including streptococci) and gram-negative coverage is essential, cefepime monotherapy is recommended as first-line therapy 5.
For community-acquired pneumonia where S. pneumoniae is suspected, cefepime 1-2g IV every 12 hours is appropriate 1, 3.
The key advantage of cefepime over third-generation cephalosporins is its dual strength: excellent streptococcal coverage comparable to cefotaxime/ceftriaxone, combined with enhanced gram-negative activity (including Pseudomonas) comparable to ceftazidime, without ceftazidime's weakness against streptococci 5, 3, 4.