Is cefoperazone (a cephalosporin antibiotic) safe to administer in patients with a penicillin allergy?

From the Guidelines

Cefoperazone can be safely administered in patients with a penicillin allergy, as the risk of cross-reactivity is estimated to be around 2% or less, according to the most recent and highest quality study 1.

Key Considerations

• The risk of cross-reactivity between penicillins and cephalosporins is generally low, especially for third-generation cephalosporins like cefoperazone.
• Patients with a history of severe or immediate allergic reactions to penicillins may still be at higher risk for cross-reactivity and should be approached with caution.
• The use of cefoperazone in patients with penicillin allergy should be guided by the severity of the allergy and the specific clinical context.

Evidence-Based Recommendations

• For patients with a confirmed penicillin allergy, the reaction rate to cefoperazone is estimated to be around 0.8% or less, based on recent studies 1.
• Cefoperazone may be used with caution in patients with mild penicillin allergies, such as delayed rashes, after consultation with an allergist or under close medical supervision.
• Alternative non-beta-lactam antibiotics like fluoroquinolones, macrolides, or aminoglycosides should be considered as safer options for penicillin-allergic patients, depending on the infection being treated and local susceptibility patterns.

Important Notes

• The risk of cross-reactivity may be higher among drugs with similar side chains, but cefoperazone has a unique side chain that may reduce the risk of cross-reactivity.
• Skin testing may not be recommended for all patients with penicillin allergy, but may be advisable for specific patients with multiple drug allergies or a history of severe reactions.

From the Research

Cefoperazone Administration in Patients with Penicillin Allergy

• Cefoperazone is a third-generation cephalosporin antibiotic, and its safety in patients with penicillin allergy is a concern due to potential cross-reactivity.
• Studies have shown that the risk of cross-reactivity between penicillins 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 2.
• Third- or fourth-generation cephalosporins, such as cefoperazone, have a negligible risk of cross-allergy with penicillins, as they have dissimilar side chains than the offending penicillin 2, 3, 4.
• A systematic review and meta-analysis found that the risk of cross-reactivity to cephalosporins varied with the degree of similarity between R1 side chains, with a lower risk associated with third-generation cephalosporins like cefoperazone 5.
• Another study found that patients with documented IgE-mediated hypersensitivity to penicillins had a low risk of cross-reactivity with third-generation cephalosporins, and all patients with negative skin test results for these cephalosporins tolerated them well 6.

Key Findings

• The risk of cross-reactivity between penicillins and cephalosporins is lower than previously reported.
• Third- or fourth-generation cephalosporins, such as cefoperazone, have a negligible risk of cross-allergy with penicillins.
• The degree of similarity between R1 side chains is a key factor in determining the risk of cross-reactivity.
• Patients with documented IgE-mediated hypersensitivity to penicillins can tolerate third-generation cephalosporins like cefoperazone well, especially if they have negative skin test results.