Is there a cross-reactivity between Cefepime (Cefepime) and Penicillin allergy?

From the Guidelines

Cefepime can generally be used safely in most patients with penicillin allergies, but caution is warranted depending on the severity of the previous allergic reaction. For patients with mild penicillin allergies (such as rash), cefepime is typically safe to administer. However, for patients with severe penicillin allergies involving anaphylaxis, angioedema, or other life-threatening reactions, there is approximately a 0.8% risk of cross-reactivity with cephalosporins like cefepime, as reported in a recent study 1. In these cases, careful risk assessment should be performed, and consideration given to either skin testing before administration, using alternative antibiotics, or administering cefepime under close monitoring in a controlled setting. The cross-reactivity occurs because both penicillins and cephalosporins share a beta-lactam ring structure, though cefepime (a fourth-generation cephalosporin) has side chains that differ significantly from penicillins, reducing the likelihood of cross-reactivity compared to earlier generation cephalosporins, as noted in a study published in the Journal of Allergy and Clinical Immunology 1. When cefepime is needed for serious infections in penicillin-allergic patients, the benefits may outweigh the risks, especially when alternative antibiotics might be less effective against the targeted pathogens. Some key points to consider include:

• The reaction rate among patients with a confirmed penicillin allergy was recently determined to be just 0.8% (95% CI: 0.13%-4.1%) among 131 patients who are confirmed to be penicillin-allergic, as reported in a study 1.
• A meta-analysis of 77 studies found that a cefazolin allergy was identified in 3.0% of patients with confirmed penicillin allergy (95% CrI: 0.01%-17.0%) 1.
• The risk of cross-reactivity to any carbapenem is low, at 0.87% (95% CI: 0.32%-2.32%), as demonstrated in a systematic review and meta-analysis covering 11 observational studies including 1127 patients 1. It is essential to weigh the potential benefits and risks of cefepime administration in penicillin-allergic patients and consider alternative treatment options, as recommended in a guideline for the approach to suspected antibiotic allergy 1.

From the FDA Drug Label

Exercise caution if this product is to be given to penicillin-sensitive patients because cross-hypersensitivity among beta-lactam antibiotics has been clearly documented and may occur in up to 10% of patients with a history of penicillin allergy.

• Cross-reactivity between Cefepime and Penicillin allergy is possible, with a reported occurrence of up to 10% in patients with a history of penicillin allergy.
• Patients with a history of penicillin allergy should be treated with caution when administering Cefepime 2, 2.

From the Research

Cross-Reactivity Between Cefepime and Penicillin Allergy

• The cross-reactivity between penicillin and cephalosporins, including Cefepime, is a topic of interest in the medical field 3, 4, 5.
• Studies have shown that the overall cross-reactivity rate between penicillins and cephalosporins is approximately 1% when using first-generation cephalosporins or cephalosporins with similar R1 side chains 3.
• However, the cross-reactivity rate can be higher for certain cephalosporins, such as cefadroxil, with a reported prevalence of cross-reactivity as high as 27% 3.
• The use of third- or fourth-generation cephalosporins, such as Cefepime, or cephalosporins with dissimilar side chains than the offending penicillin, carries a negligible risk of cross-allergy 3, 5.
• A study published in 2020 analyzed cross-reactivity with cefadroxil and cefuroxime in patients with confirmed immediate hypersensitivity reactions to amoxicillin, and found that cross-reactivity with cefadroxil was 35%, while cross-reactivity with cefuroxime was only 1.8% 6.

Factors Influencing Cross-Reactivity

• The R1 side chain is a critical factor in determining cross-reactivity between penicillins and cephalosporins 3, 5, 6.
• The involvement of the R2 side chain in IgE-mediated hypersensitivity reactions is still a topic of debate 5.
• Skin testing and drug provocation tests can be used to evaluate cross-reactivity, but may not always be predictive of an allergic reaction 4, 6.

Clinical Implications

• The risk of cross-reactivity between penicillin and cephalosporins, including Cefepime, should be carefully evaluated in patients with a history of penicillin allergy 3, 4, 5.
• The use of cephalosporins in patients with a history of penicillin allergy should be guided by the results of skin testing and drug provocation tests, as well as the specific cephalosporin being considered 4, 5.
• Clinicians should be aware of the potential for cross-reactivity between penicillins and cephalosporins, and take steps to minimize the risk of an allergic reaction in patients with a history of penicillin allergy 3, 4, 5.