Frequency of severe reactions following penicillin drug provocation tests: a Bayesian meta-analysis

Abstract

Background: Patients with a penicillin allergy label tend to have worse clinical outcomes and increased healthcare use. Drug provocation tests (DPT) are the gold-standard in the diagnostic workup of penicillin allergy, but safety concerns may hinder their performance. Objective: To assess the frequency of severe reactions following a DPT in patients with reported allergy to penicillins or other β-lactams. Methods: We performed a systematic review, searching MEDLINE, Scopus and Web of Science. We included primary studies assessing participants with a penicillin allergy label who underwent a DPT. We performed a Bayesian meta-analysis to estimate the pooled frequency of severe reactions to penicillin DPTs. Sources of heterogeneity were explored by subgroup and meta-regression analyses. Results: We included 112 primary studies which included a total of 26,595 participants. The pooled frequency of severe reactions was estimated at 0.06% (95% Credible Interval [95%CrI]=0.01-0.13%; I2=57.9%). No fatal reactions were identified. Compared to studies where the index reaction was immediate, we observed a lower frequency of severe reactions for studies assessing non-immediate index reactions (OR=0.05; 95%CrI=0-0.31). Studies performing single-dose DPTs had also lower frequency of severe reactions compared to those performing graded or prolonged DPTs (OR=0.08; 95%CrI=0-0.47). Performance of direct DPTs in low-risk patients or testing with the suspected culprit drug were not found to be associated with clinically relevant increased risk of severe reactions. Conclusion: In patients with a penicillin allergy label, severe reactions resulting from DPTs are rare. The safety of DPTs supports their performance in the diagnostic assessment of penicillin allergy.