Clavulanic acid sensitization seems more involved in cutaneous than systemic reactions in amoxicillinclavulanate drug reactions

Abstract

Background. Beta-lactams (BLs) allergy is considered a major health issue, as BLs are the most frequently involved in drug allergic reactions. Amoxicillin (AX) is the main sensitizer among all BLs. AX is commercialized alone or combined with clavulanic acid (CLA) in order to increase the antibiotic spectrum. The growing prescriptions of AX-CLA formulations contributed to increase the role of CLA as an allergy inducer. At present, little is known about the clinical characteristics of hypersensitivity reactions to clavulanate. The aim of this study was to assess the difference in the prevalence of cutaneous vs systemic reactions in patients with a documented history of allergic reactions to amoxicillin- clavulanate and tested positive for clavulanate or penicillin/amoxicillin. Methods. Between January 2017 and March 2023, out of 88 outpatients with suspected BLs allergy we selected 59 patients with a reaction to AX-CLA. Hypersensitivity reactions were classified according to onset time as immediate or delayed and according to clinical presentation as mucocutaneous or systemic reactions (anaphylaxis). All patients underwent recommended test protocols for diagnosing BLs hypersensitivity to identify the culprit drug. Sensitization was assessed through serologic and skin tests. Results. Patients whit immediate and delayed mucocutaneous reactions to AX-CLA are more sensitized to CLA 12/41 (29%) than AX or BLs determinants 9/41 (22%); on the opposite patients with immediate systemic reactions are more sensitized to AX or BLs determinants 13/18 (72%) than CLA 2/18 (11%), p less than 0.00. There was no difference in immediate vs delayed reaction regarding CLA or AX and BLs determinants sensitization. Conclusions. Our study suggests that patients who presented only muco-cutaneous reactions were more often sensitized to CLA rather than AX.

Keywords: Amoxicillin; clavulanic acid; delayed reaction; drug allergy; systemic reaction.