Does Cefepime (Cefepime) contain penicillin?

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From the Guidelines

No, Cefepime does not contain penicillin. Cefepime is a fourth-generation cephalosporin antibiotic, which belongs to a different class of beta-lactam antibiotics than penicillins. While both cephalosporins and penicillins share the beta-lactam ring structure in their chemical makeup, they are distinct medications with different antimicrobial properties and side effect profiles.

However, it's essential to consider the potential for cross-reactivity in patients with severe penicillin allergies. According to the most recent study 1, the cross-reactivity estimate between penicillins and cephalosporins is likely lower than previously thought, with a rate of around 2% based on 417 patients across 12 clinical studies conducted after 1980.

Some key points to consider:

  • Cefepime has a distinct molecular structure compared to penicillins, which reduces the likelihood of cross-reactivity 1.
  • Patients with a history of severe allergic reactions to penicillin should inform their healthcare provider before taking Cefepime, as they may have a higher risk of cross-reactivity 1.
  • The true incidence of cross-reactivity between penicillins and cephalosporins is likely to be lower than previously estimated, but it's still crucial to assess the risk and potentially choose an alternative antibiotic if necessary 1.

In terms of management, patients with a history of penicillin allergy should undergo a thorough assessment before taking Cefepime, including a review of their allergy history and consideration of alternative antibiotics if necessary 1. This approach can help minimize the risk of adverse reactions and ensure the best possible outcome for patients.

From the FDA Drug Label

CONTRAINDICATIONS Cefepime for injection is contraindicated in patients who have shown immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibiotics, penicillins or other beta-lactam antibiotics. The FDA drug label does not answer the question.

From the Research

Cefepime and Penicillin Cross-Reactivity

  • Cefepime is a fourth-generation cephalosporin antibiotic, and its cross-reactivity with penicillin is a topic of interest due to the potential for allergic reactions 2, 3, 4, 5, 6.
  • Studies have shown that the cross-reactivity between penicillin and cephalosporins is lower than previously reported, with an overall cross-reactivity rate of approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 4.
  • The R1 side chain is responsible for the cross-reactivity between penicillins and cephalosporins, and later-generation cephalosporins, such as cefepime, have distinct side chains that do not cross-react with penicillin 3, 4.
  • The use of third- or fourth-generation cephalosporins, such as cefepime, in penicillin-allergic patients carries a negligible risk of cross-allergy 4, 5.

Cefepime Structure and Allergy Risk

  • Cefepime has a distinct R1 side chain that is different from penicillin, which reduces the risk of cross-reactivity 3, 4.
  • The risk of an allergic reaction to cefepime in penicillin-allergic patients is low, and the benefits of using cefepime may outweigh the risks in certain clinical situations 5, 6.
  • Clinicians should consider the individual patient's allergy history and the specific cephalosporin being used when making treatment decisions 2, 5, 6.

Clinical Implications

  • The warning against using cephalosporins in patients with a penicillin allergy has been largely debunked, and clinicians should not avoid using cefepime or other cephalosporins solely based on a penicillin allergy history 6.
  • Evaluation of penicillin allergy before deciding not to use penicillin or other β-lactam antibiotics is an important tool for antimicrobial stewardship 5.
  • Clinicians should be aware of the low risk of cross-reactivity between penicillin and cefepime and use this information to make informed treatment decisions 2, 3, 4, 5, 6.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Cross-reactivity in β-Lactam Allergy.

The journal of allergy and clinical immunology. In practice, 2018

Research

Why Was There Ever a Warning Not to Use Cephalosporins in the Setting of a Penicillin "Allergy"?

The journal of allergy and clinical immunology. In practice, 2021

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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