Discrepancies in Beta-Lactam Antibiotics Cross-Reactivity: Implications for Clinical Practice

Background: In patients with a beta-lactam antibiotic (BA) allergy label, avoidance of the whole group of BAs leads to displacement of first-line therapies potentially influencing patient outcomes and antimicrobial resistance. Studies previously published on BA cross-reactivity use different sets of BA and seem to contain conflicting recommendations on safe BA alternatives in case of (suspected) BA allergy. Methods: The objectives were (i) to identify discrepancies between studies regarding cross-allergy in BA and (ii) to identify research gaps. The tables and errata of 4 studies (Romano et al., Trubiano et al., Zagursky et al., SWAB-guideline by Wijnakker et al.) were evaluated and compared head-to-head. Results: A total of 51 antibiotics were covered by the four authors, theoretically leading to 2550 potential recommendations regarding alternatives in case of specific allergies. Internal discrepancies existed in 2 tables. Since none of the tables included all 51 BAs, in 356 situations data were lacking regarding specific alternatives. In 1104 situations, only one author gave advice about a specific alternative. Harmony and disharmony between authors could be evaluated in 1090 cases. The advice regarding alternative BAs was 696 times in harmony (482 safe, 214 unsafe), while discrepancies were found in 394 cases. This led to a different advice (safe vs. unsafe) in 272 cases or 69%. Conclusion: Disharmony between authors was identified in 36% of the cases. In 69%, this led to a clinically relevant, different advice. This indicates the need for synchronisation of cross-reactivity tables and answering remaining research gaps.