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Updated: May 8, 2025
The Use of a β-lactamase-based Conductimetric Biosensor Assay to Detect Biomolecular Interactions
Published on: February 1, 2018
Decoding Beta-Lactam Cross-Reactivity - Longitudinal Patch Testing From 2000 to 2022
João Nuno Barbosa Soares1,2, André Aparício Martins1, Ana Carolina Figueiredo1
1Dermatology, University Hospital, Coimbra Local Health Unit, Coimbra, Portugal.
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.
