Direct drug provocation testing for the diagnosis of low‐risk pediatric beta‐lactam allergy: A risk‐stratified retrospective study

Background Beta‐lactam antibiotics remain the most commonly reported cause of drug allergy in children. Skin testing often shows limited sensitivity and logistical challenges, particularly for non‐immediate reactions, leading to the adoption of risk‐stratified diagnostic algorithms. This retrospective study evaluated the safety and diagnostic performance of a risk‐stratified approach in children with suspected beta‐lactam hypersensitivity, focusing on low‐risk non‐immediate phenotypes. Methods Medical records of 180 children (aged 3–18 years) evaluated for suspected beta‐lactam allergy were reviewed. Patients were stratified based on reaction timing and clinical phenotype. Moderate‐to‐high‐risk cases (history of anaphylaxis or immediate reactions) underwent skin testing followed by drug provocation test (DPT) if skin tests were negative. Low‐risk cases (mild maculopapular exanthema [MPE] or benign delayed‐onset urticaria occurring >6 h after dosing and lasting >24 h) underwent direct oral DPT without prior skin testing. Results Beta‐lactam hypersensitivity was confirmed in 15.6% (28/180) of patients, with higher confirmation rates in immediate reactions (21.1%) compared to non‐immediate reactions (3.5%). Among 57 low‐risk non‐immediate patients who underwent direct DPT, only 2 (3.5%) experienced mild, self‐resolving cutaneous reactions; no systemic or severe reactions were observed. No positive reactions occurred in patients with delayed‐onset urticaria (>6 h post‐dose). Conclusion Risk stratification based on detailed clinical history provides a safe and effective strategy for evaluating suspected beta‐lactam hypersensitivity in children. Direct oral DPT without preceding skin testing is safe and efficient for low‐risk non‐immediate phenotypes, including mild MPE and benign delayed‐onset urticaria, and should be more widely implemented to facilitate timely delabeling.