D1.383 - Tolerance to alternative β-lactams in patients with severe delayed skin reactions: experience in a university hospital

Severe cutaneous adverse reactions (SCAR) are delayed T-cell–mediated drug hypersensitivity reactions associated with significant morbidity. Antibiotics are among the most frequently implicated drugs, particularly β-lactams. Current recommendations advise strict avoidance of the culprit drug and structurally related compounds, which may substantially limit treatment options in patients with severe infections or relevant comorbidities. Evidence regarding tolerance to alternative β-lactams in SCAR remains limited. This study aimed to evaluate tolerance to alternative β-lactam antibiotics in patients with SCARs to β-lactams in clinically justified situations.

We conducted a retrospective study of patients with β-lactam–induced SCAR evaluated at the University Hospital of Salamanca (Spain) between 2001 and 2025. Included phenotypes were drug reaction with eosinophilia and systemic symptoms (DRESS) and acute generalized exanthematous pustulosis (AGEP). Diagnosis was established using accepted clinical criteria. All patients underwent an allergy work-up including delayed-reading patch tests and/or intradermal skin tests (STs) with the suspected culprit β-lactam and selected alternative β-lactams. Only alternatives with negative STs were considered, and controlled exposure was performed under strict medical supervision in selected cases.

Thirteen patients were included (9 DRESS and 4 AGEP), seven of whom were women. Amoxicillin was the most frequently implicated antibiotic (7/13). Four patients (33%) showed sensitization to more than one drug. In DRESS cases, STs performed with an β-lactam panel enabled identification of the culprit drug and selection of structurally related alternatives with negative STs. In AGEP-cases, only one patient showed positive STs, and alternative β-lactams with different side chains were selected. All patients tolerated an alternative β-lactam antibiotic, most commonly cephalosporins, which were successfully used in 9 of 13 patients (75%). No recurrence of SCAR or other severe delayed reactions was observed during follow-up.

Although the selection of alternative β-lactams in SCAR is challenging and drug provocation tests are generally contraindicated, some patients may tolerate structurally related β-lactams. In carefully selected cases and under strict supervision, a structured allergy work-up may allow identification of safe β-lactam alternatives, particularly in patients with limited therapeutic options.