The Safety of the Direct Drug Provocation Test in Beta-Lactam Hypersensitivity in Children: A Systematic Review and Meta-Analysis

Abstract

Background: Direct drug provocation test (DPT) without prior skin testing (ST) has been investigated in children suspected of being at risk for beta-lactam (BL) hypersensitivity reaction (HSR). However, no systematic review and meta-analysis has investigated the efficacy and safety of direct DPT for BL-HSR in children. Objective: To investigate the prevalence of BL-HSR by direct DPT and the safety of direct DPT in children. Methods: We searched MEDLINE, EMBASE, Web of Science, and CINAHL from their inception to July 23, 2022, for studies that performed direct DPT in children with suspected BL-HSR, or for studies that performed DPT in all cases with ST results, but they ignored the ST results. The true prevalence was defined as the proportion of children who experienced an HSR during direct DPT. Safety was determined according to the proportion of children who developed a dangerous reaction following DPT. Results: Twenty-eight studies with 8,334 direct challenges were included. Fifteen studies included patients who presented with either immediate or nonimmediate HSR, and the majority of the index reactions were nonsevere. Amoxicillin/amoxicillin-clavulanic acid was the most commonly used during the DPT. The pooled prevalence of confirmed BL-HSR was 5.23% (95% CI 4.17–6.39; I2 = 72%). Immediate and nonimmediate HSR were reported in 0.8% (95% CI 0.43–1.25; I2 = 55.1%) and 3.69% (95% CI 2.66-4.87; I2 = 79.77%), respectively. Severe reactions were found in 3 cases with the frequency of 0.036% (95% CI 0.012–0.112; I2 = 0%). Conclusions: The prevalence of BL-HSR by direct DPT was 5.23%, and the frequency of severe reactions from direct DPT was very low (0.036%). Our findings support direct DPT as a safe and effective delabeling tool in children with suspected nonsevere BL-HSR.