Cephalosporin allergy: R1 side-chain and penicillin cross-reactivity patterns in an Australian cohort

Cross-reactivity between cephalosporins, and penicillins, is mainly explained by R1 side-chain similarity. However, data on cross-reactivity patterns in cephalosporin-allergic patients, with and without preexisting penicillin allergy labels, are lacking.

We sought to determine whether R1 side-chain groups account for cross-reactivity between cephalosporins, and penicillins with similar R groups, in a cohort of patients with cephalosporin allergy labels, with and without a penicillin allergy history.

A retrospective audit (February 2016 to November 2021) of adult outpatients with cephalosporin allergy labels, who underwent skin prick / intradermal testing and/or oral provocation challenges, was performed at 2 Australian tertiary hospitals.

We identified 212 patients with a single cephalosporin allergy label; 97 had coexisting penicillin allergy labels. Fifty-eight (27.4%) patients were confirmed as allergic to the index cephalosporin (47 to cefazolin). The cephalosporin skin testing and oral provocation challenge results were adequately explained by R1 side-chain patterns. Most (87.5%) of the cephalosporin-allergic patients with penicillin allergy labels tolerated a penicillin challenge and were delabelled. However, positive penicillin skin test results were found in 5 (10.2%) cefazolin-allergic patients without preexisting penicillin allergy labels.

R1 side-chain groups explained most test outcomes in this study. However, some positive penicillin skin testing results were identified without a history of penicillin allergy. Future research investigating the safety of supervised graded penicillin challenges in cephalosporin-allergic patients is needed.