Does cefepime provide coverage against Enterococcus species in urine?

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Last updated: December 22, 2025View editorial policy

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Cefepime Does NOT Cover Enterococcus in Urine

No, cefepime has no clinically useful activity against Enterococcus species and should never be used as monotherapy when enterococcal urinary tract infection is suspected or confirmed. 1, 2

Microbiological Basis for Lack of Coverage

  • Cephalosporins, including cefepime, have minimal or no in vitro activity against enterococci, making them fundamentally inappropriate for treating Enterococcus faecalis infections 1
  • The FDA drug label explicitly states that "most isolates of enterococci, e.g., Enterococcus faecalis, are resistant to cefepime" 2
  • The American Heart Association specifically recommends against using cephalosporins for enterococcal infections due to their complete lack of intrinsic activity 1

Appropriate Treatment Options for Enterococcal UTI

When enterococcal coverage is needed for urinary tract infections, the following agents should be used:

First-Line Agents for Uncomplicated UTI

  • Nitrofurantoin is FDA-approved specifically for E. faecalis urinary tract infections, with resistance rates below 6% 1
  • Fosfomycin is FDA-approved for uncomplicated E. faecalis UTIs at a 3g oral single dose 1

Systemic Therapy Options

  • Ampicillin or amoxicillin remains the drug of choice for enterococcal infections, with clinical and microbiological eradication rates of 88.1% and 86% respectively 1
  • Vancomycin can be used for ampicillin-resistant strains, particularly in healthcare-associated infections 1

When to Add Enterococcal Coverage to Cefepime Regimens

If cefepime is being used for gram-negative coverage in a patient at risk for enterococcal infection, ampicillin, piperacillin-tazobactam, or vancomycin must be added 1:

High-Risk Scenarios Requiring Enterococcal Coverage

  • Healthcare-associated intra-abdominal infections 1
  • Postoperative infections 1
  • Patients previously treated with cephalosporins 1
  • Immunocompromised patients 1
  • Patients with valvular heart disease or prosthetic intravascular materials 1

Critical Clinical Pitfall

Using cefepime monotherapy for suspected or confirmed enterococcal infections represents treatment failure from the outset 1. The Surgical Infection Society emphasizes that empiric anti-enterococcal coverage is mandatory for healthcare-associated infections when specific risk factors are present 1.

Evidence from Combination Therapy Studies

While one in vitro study demonstrated that ampicillin-cefepime combinations showed activity against E. faecalis similar to ampicillin-ceftriaxone 3, this does not indicate that cefepime itself has enterococcal activity—the ampicillin component provides all the anti-enterococcal effect 3.

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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