Safe Penicillin Allergy Delabeling in Primary Care: A Systematic Review and Meta-Analysis

Background Ten % of the population is labeled as allergic to penicillin(s), when in fact 90% of these labels are inappropriate. Recent studies have shown that inpatient de-labelling by a direct drug challenge (dDC) is safe in low-risk patients. However, there is a need for outpatient and non-allergist de-labelling. Objective To assess the safety of de-labelling low-risk adults by means of dDC in primary care. Methods We searched MEDLINE, EMBASE and the Conchrane Library databases, from inception to March 15, 2022 (updated June 5, 2023) for studies performing dDC in adults in primary care or other outpatient settings. Two researchers independently screened studies for eligibility. The data extraction and critical appraisal was performed by one reviewer and we pooled the results in a meta-analysis. Results Out of 2,138 results, 12 studies (1070 participants) were eligible for inclusion. Three studies evaluated de-labelling in primary care and 9 studies in an outpatient hospital setting. There were no critical adverse events during dDC. No reaction occurred in 97.13% of the 1070 patients, who previously labeled as penicillin-allergic, and were safely de-labelled. Ten patients (<1%) developed an immediate reaction: three had self-limiting reactions, and seven needed antihistaminics, steroids, epinephrine and/or salbutamol. Conclusion No serious allergic reactions are observed during direct amoxicillin challenge in adults in an outpatient setting. However, with the exception of one recent report, these studies are of low to moderate quality. Non-specialist de-labelling is promising but further research is required on correct risk stratification and safety assessment in large cohort studies evaluating dDC in primary care.