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

Witchaya Srisuwatchari; Phichayut Phinyo; Anca Mirela Chiriac; Surasak Saokaew; Prapasri Kulalert

doi:10.1016/j.jaip.2022.11.035

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

J Allergy Clin Immunol Pract. 2023 Feb;11(2):506-518. doi: 10.1016/j.jaip.2022.11.035. Epub 2022 Dec 14.

Authors

Witchaya Srisuwatchari¹, Phichayut Phinyo², Anca Mirela Chiriac³, Surasak Saokaew⁴, Prapasri Kulalert⁵

Affiliations

¹ Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
² Center for Clinical Epidemiology and Clinical Statistics, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Department of Family Medicine, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand; Musculoskeletal Science and Translational Research (MSTR), Chiang Mai University, Chiang Mai, Thailand.
³ Division of Allergy, Department of Pulmonology, Hôpital Arnaud de Villeneuve, University Hospital of Montpellier, Montpellier, France; IDESP, UMR UA11, University of Montpellier, INSERM, Montpellier, France.
⁴ UNIt of Excellence on Clinical Outcomes Research and IntegratioN (UNICORN), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand.
⁵ Department of Clinical Epidemiology, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand; Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Thammasat University, Pathum Thani, Thailand. Electronic address: prapasrikulalert@gmail.com.

PMID: 36528293
DOI: 10.1016/j.jaip.2022.11.035

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.

Keywords: Beta-lactam hypersensitivity reaction; Children; Direct drug provocation test; Drug hypersensitivity; Meta-analysis; Prevalence; Systematic review.

Publication types

Meta-Analysis
Systematic Review

MeSH terms

Amoxicillin-Potassium Clavulanate Combination
Anti-Bacterial Agents* / adverse effects
Child
Drug Hypersensitivity* / diagnosis
Drug Hypersensitivity* / epidemiology
Humans
Skin Tests / methods
beta-Lactams / adverse effects

Substances

Anti-Bacterial Agents
beta-Lactams
Amoxicillin-Potassium Clavulanate Combination