Decoding Beta-Lactam Cross-Reactivity - Longitudinal Patch Testing From 2000 to 2022.

Abstract

Introduction: Patients with non-immediate hypersensitivity to beta-lactam antibiotics (βL) often avoid all βL, with limitations for future therapy.

Objectives: Assess cross-reactivity between βL in non-immediate cutaneous adverse drug reactions (ni-CADRs).

Methods: Retrospective analysis (2000-2022) of patients with suspected ni-CADR with βL as a possible culprit who underwent patch testing (PT) with an extended antibiotic series (10% pet., Chemotechnique Diagnostics or prepared in-house) according to European Society of Contact Dermatitis (ESCD) recommendations. Fisher exact test was used with a significance of 0.05 corrected for multiple testing; positive associations were quantified with odds ratio (OR) with 95% confidence interval (CI).

Results: Four hundred and fourteen patients (270 female/144 male; age 52 ± 19 years) were included, mostly with maculopapular exanthema (367; 89%), drug reaction with eosinophilia and systemic symptoms (DRESS) (22; 5%) and acute generalised exanthematous pustulosis (AGEP) (12; 3%). Eighty-six patients (21%) had positive results to at least one drug. Fifty-eight patients (14%) had 110 positive results to βL, mostly amoxicillin (33). Co-reactivity within penicillins was almost universal, including piperacillin with other penicillins (p = 0.007; OR 25; CI 3-56). There was co-reactivity to aminopenicillins and aminocephalosporins (p = 0.006; OR 33; CI 4-74) and within the cephalosporin subclass, including between aminocephalosporins and non-aminocephalosporins. Within carbapenems, 1 patient reacted to meropenem and ertapenem, with no extension to imipenem, as confirmed with a provocation test. Two patients reacted both to ceftriaxone and meropenem (p = 0.013; OR: 68; CI:15-612).

Conclusion: PT is useful to confirm a probable culprit in ni-CADR to βL. Co-reactivity, interpreted mostly as cross-reactivity, occurred within cephalosporin and, particularly, with penicillin subclasses, including between piperacillin-tazobactam and remaining penicillins, which has seldom been described. There was no association between penicillins and cephalosporins as a whole, except between aminopenicillins and aminocephalosporins, attributable to a similar lateral chain amino group. We found an unexpected association between meropenem and ceftriaxone, probably a concomitant sensitization.