Penicillin Allergy Delabeling: Bridging the Evidence-Practice Gap in Antimicrobial Stewardship

Penicillin allergy labels are common and clinically consequential. Approximately 10% of patients report a penicillin allergy, yet most are not truly allergic and can safely receive beta-lactams. In the inpatient setting, these labels drive use of broader-spectrum agents, contributing to increased healthcare-associated infections, antimicrobial resistance, longer hospital stays, and higher costs. Recent evidence supports delabeling as a key antimicrobial stewardship strategy. The PEN-FAST clinical decision rule enables identification of low-risk patients suitable for streamlined evaluation. The PALACE randomized trial demonstrated that, among low-risk adults, direct oral penicillin challenge is noninferior to traditional skin testing and associated with very low rates of adverse reactions. This narrative review summarizes current evidence on epidemiology, mechanisms, risk stratification, and delabeling strategies, and provides practical recommendations for integrating penicillin allergy delabeling into routine clinical practice.