Resensitization of β-Lactams After Negative Initial Standard Evaluation: A Systematic Review and Meta-Analysis
After a negative supervised allergy evaluation, repeat testing for beta-lactam allergy finds few new allergies and severe reactions are rare.
*Systematic review and meta-analysis of observational studies; Level 1a (OCEBM).
*Systematic review and meta-analysis of observational studies; Level 1a (OCEBM).
Citation
Srisuwatchari W, Kulalert P, Krikeerati T, et al. Resensitization of β-Lactams After Negative Initial Standard Evaluation: A Systematic Review and Meta-Analysis. Journal of Allergy and Clinical Immunology: In Practice. 2026;14:1373-1386. doi:10.1016/j.jaip.2026.02.012
Background
Most people labeled as allergic to beta-lactam antibiotics can later take these drugs safely after a supervised evaluation. Whether allergy can “return” after a negative evaluation is uncertain, leading to debate about retesting.
Patients
People with a documented history of beta-lactam allergy who had a negative initial standard evaluation confirming tolerance; studies without clear initial evaluation or retesting methods were excluded.
Intervention
Retesting after the negative evaluation, mainly with supervised drug provocation (either direct or after skin testing).
Control
No single control group; results were summarized overall and by retesting method.
Outcome
Resensitization (new positive retest or reaction on re-exposure) and severe reactions during retesting.
Follow-up Period
Time from negative evaluation to retesting ranged from 2 weeks to several years.
Results
| Analysis group | Resensitization rate (95% confidence interval) | Number needed to retest to detect 1 case | Severe reaction rate during retesting |
|---|---|---|---|
| All included studies (32 studies; 5766 retests) | 3.80% (2.35% to 5.50%) | — | 0.26% |
| Supervised drug provocation retesting (8 studies; 3414 retests) | 2.44% (0.99% to 4.43%) | 41 | 0.32% |
Evidence certainty for the main resensitization estimate was low.
Limitations
Included studies varied widely in who was retested, how retesting was done, and how “resensitization” was defined, making results less precise. Some retesting relied on skin or blood tests that can be falsely positive, possibly inflating rates.
Funding
No funding reported; authors reported no relevant conflicts.
Clinical Application
Do not routinely retest patients after a negative supervised beta-lactam evaluation; consider individualized retesting mainly for prior anaphylaxis or high-risk future exposures.
Discussion
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In this systematic review/meta-analysis of mostly observational studies, DPT-based retesting after a negative β-lactam evaluation found resensitization 2.44% (≈1 per 41 retests) with severe reactions 0.32% but high heterogeneity (I²≈86%); does this justify not retesting routinely, and for whom (eg, prior anaphylaxis) might applicability differ? The authors used a random-effects model to pool resensitization prevalence and reported substantial heterogeneity (eg, I²≈86% in the DPT subgroup). What is the best interpretation of that choice?