Abstract
OBJECTIVE: Penicillin allergies are reported in 10-15% of the US population, but the actual rate is less than 1%. Inappropriate penicillin allergies are associated with adverse patient outcomes, poor antimicrobial stewardship, and increased healthcare costs. Direct oral provocation testing (DOPT) is a safe and cost-effective way to remove false penicillin allergy labels (PAL). However, widespread implementation is currently limited due to inadequate safety data and protocol variations. This systematic review evaluates the safety of single-dose, nongraded DOPT by the nonallergist. DESIGN: Systematic review. MEDLINE, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were searched from inception to May 2025. SETTING: Inpatient (Intensive care unit (ICU) and general medical ward) and outpatient. PARTICIPANTS: Adults with self-reported penicillin allergies deemed low risk by a validated scoring system. INTERVENTIONS: DOPT by nonallergists with single-dose oral amoxicillin 250 mg with a 60-minute observation period. RESULTS: 3 352 studies were identified, 15 were included in the analysis. Of the 1786 patients who completed DOPT, 66 (3.7%) experienced any reaction: 27 (1.5%) immediate rashes, 24 (1.3%) delayed rashes, and 15 (.8%) other reactions. No cases of anaphylaxis, angioedema, or epinephrine use were reported. CONCLUSION: The use of single-dose DOPT in patients deemed low risk, using a validated risk scoring tool, is safe, with low rates of mild reactions and no serious adverse events. A nonallergist can significantly improve penicillin delabeling rates and patient outcomes using this approach.