Does cefepime cover gram‑positive aerobic cocci that appear in pairs (Enterococcus) or chains (streptococci)?

Cefepime Coverage of Gram-Positive Aerobic Cocci in Pairs and Chains

Cefepime provides excellent coverage against streptococci (chains) but has NO clinically useful activity against enterococci (pairs), requiring the addition of ampicillin or vancomycin when enterococcal coverage is needed. 1, 2, 3

Coverage Against Streptococci (Chains)

Cefepime is highly active against streptococcal species and is recommended by the Infectious Diseases Society of America for streptococcal infections. 2

• Cefepime demonstrates excellent in vitro activity against Streptococcus pneumoniae (including penicillin-resistant strains), Streptococcus pyogenes (Group A strep), and viridans group streptococci. 2, 3
• The FDA label explicitly lists these streptococcal species as covered organisms for which cefepime has been shown to be active both in vitro and in clinical infections. 3
• Cefepime's potency against streptococci is superior to third-generation cephalosporins like ceftazidime, though slightly less than ceftriaxone. 2
• Clinical studies confirm cefepime effectively treats streptococcal infections in neutropenic patients and other high-risk populations. 2

Complete Lack of Coverage Against Enterococci (Pairs)

Cefepime has minimal to no activity against enterococci and should NEVER be used as monotherapy when enterococcal infection is suspected or confirmed. 1, 3

• The FDA label explicitly states that "most isolates of enterococci, e.g., Enterococcus faecalis, are resistant to cefepime." 3
• The American Heart Association recommends against using any cephalosporin, including cefepime, for enterococcal infections due to their lack of intrinsic activity. 1
• Multiple research studies confirm cefepime has poor to no activity against enterococci, with only 44.4% of isolates inhibited even at high concentrations of 8 mg/L. 4

When to Add Anti-Enterococcal Coverage to Cefepime

You must add ampicillin, piperacillin-tazobactam, or vancomycin to cefepime-based regimens in the following high-risk scenarios: 1

• Healthcare-associated or postoperative intra-abdominal infections 1
• Patients previously treated with cephalosporins or other broad-spectrum antibiotics 1
• Immunocompromised patients 1
• Patients with valvular heart disease or prosthetic intravascular materials 1
• Biliary-enteric anastomosis 1

Recommended Anti-Enterococcal Agents

• Ampicillin 2 g IV every 4-6 hours is the drug of choice for E. faecalis infections, with clinical eradication rates of 88.1%. 5, 1
• Vancomycin should be used for ampicillin-resistant strains, particularly in healthcare-associated infections. 5, 1
• Piperacillin-tazobactam provides both gram-negative and enterococcal coverage and may be preferred over cefepime when enterococcal risk is present. 5, 1

Critical Clinical Pitfall

The most common error is using cefepime monotherapy for polymicrobial infections without recognizing enterococcal risk factors. 1 For intra-abdominal infections, cefepime must be combined with metronidazole for anaerobic coverage AND ampicillin when enterococcal risk factors are present. 5, 1