Is cefepime (a fourth-generation cephalosporin antibiotic) contraindicated in patients with a history of anaphylaxis to penicillin?

From the Guidelines

Cefepime is not absolutely contraindicated in patients with a history of anaphylaxis to penicillin, but it should be used with caution due to a potential cross-reactivity risk of around 1% or less, as indicated by recent studies 1. When considering the use of cefepime in patients with a penicillin allergy history, it's crucial to weigh the benefits against the risks. The cross-reactivity between penicillin and cephalosporins, including fourth-generation agents like cefepime, is a concern but has been found to be relatively low, around 1% or less, especially in patients with confirmed penicillin allergy 1. Key factors influencing this decision include the severity of the original penicillin reaction, the time elapsed since the reaction, and the current clinical needs of the patient.

Considerations for Use

• Severity of Original Reaction: Patients with a history of anaphylaxis to penicillin are at a higher risk of severe reactions to cephalosporins. However, the risk with fourth-generation cephalosporins like cefepime is considered lower compared to earlier generations 1.
• Time Elapsed: The risk of cross-reactivity may decrease over time, but this factor should be considered in the context of the patient's overall allergy history and current clinical status.
• Clinical Needs: The decision to use cefepime should be based on whether it is the best antibiotic choice for the patient's specific infection, considering factors like susceptibility patterns and the potential for alternative treatments.

Approach to Administration

If cefepime is deemed necessary and no suitable alternatives are available, several steps can be taken:

• Consultation with an Allergist: For patients with a history of penicillin anaphylaxis, consulting an allergist for potential desensitization protocols or to assess the risk of cross-reactivity can be beneficial 1.
• Skin Testing: Although not universally recommended or available, skin testing may help assess individual risk, particularly in cases where the history of penicillin allergy is uncertain or when evaluating the risk of cross-reactivity to specific cephalosporins like cefepime 1.
• Controlled Administration: In situations where cefepime is critically needed, especially in emergency settings, administration should occur in a controlled environment with capabilities for resuscitation and close monitoring of the patient for signs of an allergic reaction.

Documentation and Decision-Making

The decision to use cefepime in a patient with a history of penicillin anaphylaxis should be carefully documented, including the rationale for its use, the assessment of the risk of cross-reactivity, and the measures taken to mitigate this risk. This approach ensures that the use of cefepime is justified and that the patient receives the best possible care while minimizing the risk of adverse reactions 1.

From the FDA Drug Label

CONTRAINDICATIONS • Prior immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibacterial drugs, penicillins, and other beta-lactam antibacterial drugs. (4) Cefepime Injection is contraindicated in patients who have shown immediate hypersensitivity reactions to cefepime or the cephalosporin class of antibacterials, penicillins or other beta-lactam antibacterial drugs. Before therapy with Cefepime Injection is instituted, careful inquiry should be made to determine whether the patient has had previous immediate hypersensitivity reactions to cefepime, cephalosporins, penicillins, or other beta-lactams

Cefepime is contraindicated in patients with a history of immediate hypersensitivity reactions to penicillins, as there is a risk of cross-hypersensitivity among beta-lactam antibacterial drugs, which may occur in up to 10% of patients with a history of penicillin allergy 2, 2, 2.

From the Research

Cefepime and Penicillin Allergy

• Cefepime is a fourth-generation cephalosporin antibiotic, and its use in patients with a history of anaphylaxis to penicillin is a concern due to the potential for cross-reactivity between penicillin and cephalosporins 3, 4, 5.
• However, studies have shown that the incidence of adverse reactions to cephalosporins in patients with a history of penicillin allergy is low, ranging from 1% to 10% 3, 5.
• A study published in 2005 found that none of the patients who received a fourth-generation cephalosporin, such as cefepime, reacted to the antibiotic 5.
• Another study published in 2021 noted that avoiding β-lactam antibiotics, including cephalosporins, due to a penicillin allergy can result in worse long-term global outcomes for patients, and that the risks of avoiding cephalosporins outweigh the benefits 4.
• The American College of Allergy, Asthma, and Immunology has stated that cephalosporins can be safely administered to patients with a history of penicillin allergy, except in cases where the patient has a history of a severe, life-threatening reaction to penicillin 6, 3.

Cross-Reactivity between Penicillin and Cephalosporins

• The cross-reactivity between penicillin and cephalosporins is estimated to be around 1-16% 5.
• However, this cross-reactivity is more likely to occur with first-generation cephalosporins, such as cefadroxil, which has an amino benzyl side chain 5, 7.
• Fourth-generation cephalosporins, such as cefepime, have a lower risk of cross-reactivity due to their different chemical structure 5.

Recommendations for Use

• Cefepime can be used in patients with a history of anaphylaxis to penicillin, but caution should be exercised and the patient should be closely monitored for any signs of an allergic reaction 3, 4, 5.
• Patients who have a history of a severe, life-threatening reaction to penicillin should avoid cephalosporins, including cefepime, unless absolutely necessary and under close medical supervision 6, 3.