Is a Prolonged Drug Provocation Test Better Than a Single-Day Drug Provocation Test? A Systematic Review and Meta-Analysis

BACKGROUND: There is currently no standardized duration of drug provocation test (DPT) for confirming/delabeling betalactam hypersensitivity reaction (BL-HSR). OBJECTIVES: This meta -analysis and systematic review aimed to investigate the added diagnostic value of extended -day over single -day DPT for confirming/delabeling BL-HSR in adults and children. METHODS: The MEDLINE, EMBASE, Web of Science, and CINAHL online databases were searched from inception to March 15, 2023, for studies that performed extended -day DPT to confirm/delabel BL-HSR. Risk difference and risk ratio were used to compare the proportions of patients with confirmed BLHSR by single -day or extended -day DPT. RESULTS: A total of 10,371 DPTs from 42 studies were included. Extended -day DPTs ranged from 2 to 7 days, or as long as index reactions were reported (maximum 10 days). The overall prevalence of confirmed BL-HSR was 6.96% (3.31% during the first-day DPT, and 3.65% during extended -day DPT). Approximately half of the positive reactions during extended -day DPT occurred during the second/third day. The increased detected pool prevalence of confirmed BL-HSR yielded by extended -day DPT was 0.03 (95% CI, 0.02%-0.04%; I-2 = 57.69%; P < .001), and the risk ratio of positive reactions between extended -day and single -day DPT was 1.94 (95% CI, 1.62-2.33; I-2 = 36.26%; P < .001). The risk difference increased per 1% increase in prevalence of BL-HSR by 0.6% (95% CI, 0.4%-0.7%; P < .001). Twenty-three severe reactions occurred during DPT, and only 2 severe reactions (0.02%) occurred during extended -day DPT. An additional 28 extended -day DPTs were needed to identify 1 mild reaction. CONCLUSIONS: The increased prevalence of confirmed BLHSR observed during extended -day DPT could be attributed to the first-day DPT. As a result, our findings do not conclusively support the use of extended -day DPT over single -day DPT. Further studies, incorporating a washout period, are required to comprehensively compare these 2 approaches. (c) 2023 American Academy of Allergy, Asthma & Immunology (J Allergy Clin Immunol Pract 2024;12:431-48)