Deconstructing Adverse Reactions to Amoxicillin- Clavulanic Acid: The Importance of Time of Onset

Amoxicillin-clavulanic acid (AX-CL) is the most consumed ß-lactam antibiotic worldwide. We aimed to establish the different phenotypes of ß-lactam allergy in patients reporting a reaction to AX-CL and to investigate the differences between immediate and nonimmediate onset.

We performed a cross-sectional retrospective study at Hospital Clínico San Carlos (HCSC), Madrid and Hospital Regional Universitario de Málaga (HRUM), Málaga, Spain. We included patients reporting reactions with AX-CL who underwent the allergy workup between 2017 and 2019. Data on the reported reaction and allergy work-up were collected. Reactions were classified as immediate and nonimmediate with a 1-hour cut-off.

The study population comprised 372 patients (HCSC 208, HRUM 164). There were 90 immediate reactions (24.2%), 252 nonimmediate reactions (67.7%), and 30 reactions with unknown latency (8.1%). Allergy to ß-lactams was ruled out in 266 patients (71.5%) and confirmed in 106 patients (28.5%). The final main diagnosis in the overall population was allergy to aminopenicillins (7.3%), to CL (7%), to penicillin (6.5%), and to ß-lactams (5.9%). Allergy was confirmed in 77.2% and 14.3% of immediate and nonimmediate reactions, respectively, with a relative risk of 5.06 (95%CI, 3.64-7.02) for an allergy diagnosis in those reporting immediate reactions. Only 2/54 patients with a late-positive intradermal test (IDT) result for CL were diagnosed with CL allergy.

Allergy was diagnosed in a minority of the study population. However, given that it was diagnosed 5 times more frequently in patients reporting immediate reactions, this classification proved useful for risk stratification. Late-positive IDT results for CL have no diagnostic value. Therefore, the late IDT reading for CL could be removed from the diagnostic work-up.