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

Journal: The journal of allergy and clinical immunology. In practice 2023;11(2):506-518

PMID: 36528293

Full Text on Elsevier Science View on PubMed

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; I = 72%). Immediate and nonimmediate HSR were reported in 0.8% (95% CI 0.43-1.25; I = 55.1%) and 3.69% (95% CI 2.66-4.87; I = 79.77%), respectively. Severe reactions were found in 3 cases with the frequency of 0.036% (95% CI 0.012-0.112; I = 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.

Address: Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.; 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.; 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.; UNIt of Excellence on Clinical Outcomes Research and IntegratioN (UNICORN), School of Pharmaceutical Sciences, University of Phayao, Phayao, Thailand.; 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: [email protected].

DOI: 10.1016/j.jaip.2022.11.035

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MeSH Terms: Humans, Child, Anti-Bacterial Agents, beta-Lactams, Drug Hypersensitivity, Skin Tests, Amoxicillin-Potassium Clavulanate Combination