Can metronidazole (MET) intravenous (IV) be co-administered with cefepime (CEF) intravenous (IV)?

Metronidazole IV and Cefepime IV Can Be Co-administered

Yes, metronidazole IV and cefepime IV can be safely co-administered. This combination is specifically FDA-approved for complicated intra-abdominal infections and is supported by clinical guidelines.

Evidence Supporting Co-administration

The FDA label for cefepime explicitly states that cefepime is indicated for "complicated intra-abdominal infections (used in combination with metronidazole)" 1. This combination has been clinically tested and shown effective against various pathogens including Escherichia coli, viridans group streptococci, Pseudomonas aeruginosa, Klebsiella pneumoniae, Enterobacter species, and Bacteroides fragilis 1.

Multiple clinical guidelines support this combination:

• The Infectious Diseases Society of America (IDSA) guidelines for skin and soft tissue infections recommend ceftriaxone plus metronidazole for surgery of intestinal or genitourinary tract 2.
• The Surgical Infection Society and IDSA guidelines for intra-abdominal infections specifically list cefepime in combination with metronidazole as an appropriate regimen for health care-associated infections 2.
• The ESMO guidelines for neutropenic enterocolitis recommend cefepime along with metronidazole as reasonable initial therapy 2.

Clinical Efficacy

A randomized, double-blind clinical trial demonstrated that the combination of cefepime (2g IV every 12 hours) plus metronidazole (500mg IV every 6 hours) was not only effective but actually showed higher cure rates (88%) compared to imipenem-cilastatin (76%) in treating complicated intra-abdominal infections 3. This study provides strong evidence for the efficacy of this combination.

Stability and Compatibility

Research specifically examining the physical compatibility of cefepime and metronidazole as a single admixture found that:

• When mixed together, cefepime and metronidazole maintain stability:
  • At 4°C (refrigerated), the combination remains stable for up to 336 hours (14 days)
  • At 23°C (room temperature), stability is maintained for 48-72 hours depending on concentration 4

This stability data supports that these medications can be co-administered either sequentially or as a single admixture.

Administration Recommendations

When administering these medications:

1. Sequential administration: Administer each drug separately through the same IV line with appropriate flushing between medications
2. Y-site administration: Both drugs can be administered simultaneously through a Y-site connector
3. Admixture: For certain situations, they can be prepared as a single admixture, though this is less common in practice

Dosing Considerations

For complicated intra-abdominal infections, the typical dosing is:

• Cefepime: 2g IV every 12 hours (or every 8 hours for severe infections)
• Metronidazole: 500mg IV every 6-8 hours

Important Precautions

• While the drugs are compatible, avoid preparing admixtures that will be stored at temperatures above 25°C for extended periods
• Do not mix either drug with incompatible medications such as erythromycin, propofol, midazolam, or phenytoin 5
• Monitor for adverse effects of either medication, including potential neurotoxicity with cefepime (especially in patients with renal impairment)

This combination provides excellent coverage against both aerobic gram-negative bacteria (from cefepime) and anaerobic bacteria (from metronidazole), making it an effective choice for mixed infections.