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

Area of Science:

• Allergy and Immunology
• Pharmacology
• Clinical Medicine

Background:

• Beta-lactam (BL) allergy diagnosis and retesting strategies lack standardization.
• Methodological heterogeneity complicates risk assessment for BL resensitization post-negative testing.
• This leads to ongoing debate regarding recommendations for retesting BL-allergic patients.

Purpose of the Study:

• To systematically review and meta-analyze the prevalence and severity of BL resensitization.
• To identify determinants of BL resensitization.
• To inform safe and individualized retesting strategies for beta-lactam allergy.

Main Methods:

• Searched PubMed, EMBASE, Scopus, and CINAHL up to August 2024.
• Included studies of patients with documented BL allergy and negative initial standard evaluation (NISE).
• Employed random-effects models for pooled prevalence and subgroup analyses; assessed evidence strength using GRADE.

Main Results:

• Analyzed 32 studies with 5,766 retests; overall pooled resensitization rate was 3.80%.
• Studies using sequential or direct drug provocation tests (DPT) showed a 2.44% resensitization rate (1 per 41 retests).
• Severe reactions during DPT retesting occurred in 0.32%; strength of evidence for prevalence was low.

Conclusions:

• The pooled resensitization risk following a negative beta-lactam allergy evaluation, particularly with DPT, is low (1-4%).
• Serious adverse events during retesting are infrequent.
• Findings suggest routine retesting is not warranted, as the risk is comparable to de novo reactions in the general population.