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 beta-lactam 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 15 March 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 BL-HSR by single-day or extended-day DPT.

RESULTS: A total of 10,371 DPTs from 42 studies were included. Extended-day DPTs ranged from 2-7 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 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%; I2 =57.69%, p<0.001), and the risk ratio of positive reactions between extended-day and single-day DPT was 1.94 (95%CI: 1.62-2.33; I2 =36.26%, p<0.001). The risk difference increased per 1% increase in prevalence of BL-HSR by 0.6% (95%CI: 0.4-0.7%; p<0.001). Twenty-three severe reactions occurred during DPT, with only 2 severe reactions (0.02%) occurred during extended-day DPT. Additional 28 extended-day DPTs were needed to identify one mild reaction.

CONCLUSION: The increased prevalence of confirmed BL-HSR observed during extended-day DPT could be attributed to the first-day DPT. As a results, our findings do not conclusively support the use of extended-day DPT over single-day DPT. Further studies, incorporating a wash out period, are required to comprehensively compare these two approaches.