Resensitization of β-Lactams After Negative Initial Standard Evaluation: A Systematic Review and Meta-Analysis

β-Lactam (BL) allergy workup varies across studies because of methodological heterogeneity, which affects the estimated risk of BL resensitization after a negative allergy test. Consequently, controversy remains regarding recommendations for retesting.

This systematic review and meta-analysis aimed to quantify the prevalence, severity, and determinants of BL resensitization to support safe and individualized retesting strategies.

PubMed, Embase, Scopus, and CINAHL were searched from inception to August 4, 2024, in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Eligible studies enrolled patients with documented BL allergy who achieved a negative initial standard evaluation confirming tolerance and subsequently underwent retesting. Random-effects models generated pooled prevalence with 95% confidence intervals (CIs); subgroup analyses examined retest modality, reaction chronology, geography, and age. The strength of evidence was graded with Grading of Recommended Assessment, Development, and Evaluation (GRADE).

Thirty-two studies comprising 5766 retests met eligibility criteria. The overall pooled resensitization rate was 3.80% (95% CI, 2.35-5.50; I² = 82.96%). Limiting to studies using the sequential or direct drug provocation test (DPT) across 3414 retesting evaluations, the resensitization rate was 2.44% (95% CI, 0.99-4.43; I² = 86.08%), equivalent to 1 case detected per 41 retests. Severe reactions during retesting with these methods occurred at a rate of 0.32% (95% CI, 0.18-0.58; I² = 0.0%). The overall strength of evidence for resensitization prevalence was graded as low.

In DPT-based studies, the pooled resensitization risk was low (approximately 1%-4%) with substantial heterogeneity. Serious reactions during retesting were very rare. These findings do not support routine retesting after a negative evaluation, as the observed risk is in the range of de novo BL reactions in the general population.