The safety of initial single therapeutic dose challenge with a 5-day prolonged drug provocation test in children with a history of low-risk non-immediate reactions to beta-lactam antibiotics.

Background: Although the gold standard for diagnosing beta-lactam antibiotic (BLA) allergy is the drug provocation test (DPT), there is no standardized protocol for children. Objective: We aimed to evaluate the clinical features and DPT results of children with a history of low-risk non-immediate reactions (NIR) to BLA who underwent initial direct single therapeutic dose challenge with a 5-day prolonged DPT. Methods: We retrospectively evaluated children ages 0-18 years with a history of low-risk NIRs to BLAs. On the first day of provocation, a single-dose DPT protocol without any skin test was administered at the clinic. The therapeutic dose was adjusted to not exceed the maximum single-unit dose (MSUD) for age and weight. The DPT protocol was administered with 100% of MSUD. To identify children with delayed reactions, the parents or caregivers were told to continue giving the medication at home for 5 days. Results: One hundred and nine children were included in this study. The median (interquartile range) age of the children was 62.5 months (26.5-94 months). Of the suspected drugs, the main culprit drug was amoxicillin-clavulanic acid for 89 children (81.7%). The most common clinical manifestation was maculopapular exanthema, which occurred in 85 children (78%), and 8 (7.3%) had a positive DPT result. Three children (2.8%) developed a reaction after the first DPT dose. The remaining children continued to use the suspected BLA at home. Five children (4.7%) developed a reaction while using the drug at home. All the children with positive DPT results developed mild cutaneous signs and presented with a reaction to amoxicillin-clavulanic acid. None had a systemic or severe cutaneous reaction. Conclusion: Initial direct single therapeutic dose challenge with a 5-day prolonged DPT is a useful and safe way to assess low-risk NIRs to BLAs in children.