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.