BackgroundBeta-lactam antibiotic allergy labels are highly prevalent but rarely indicate an allergic intolerance. These patient-reported allergies lead to broad-spectrum antibiotic use, conferred resistance, increased expense, and adverse effects. ObjectiveTo implement and assess the impact of a history-based clinical guideline that directs antibiotic management and beta-lactam allergy relabeling for patients reporting beta-lactam allergies. MethodsPatients with beta-lactam allergy labels were identified by our trained multidisciplinary team in diverse clinical settings. This quality improvement project was conducted to evaluate the safety and impact of the guideline on antibiotic use by comparing prescribing practices before and after guideline implementation. ResultsA total of 79 patients with beta-lactam allergies were identified (penicillins-90%, cephalosporins-10%). After guideline implementation, outcomes of allergy relabeling included the following: (1) complete removal, indicating an unlikely true allergy (27%); (2) updated to detail successfully tolerated beta-lactam courses (48%); or (3) no change made to current label (25%). Beta-lactam antibiotic courses before and after guideline implementation compared with total antibiotic courses: allergy removed (44% vs 70%; P < .001), allergy updated (32% vs 68%; P < .001), and no change (27% vs 41%; P = .08). Compared with before guideline implementation, beta-lactam antibiotics were 3 times more likely to be prescribed after allergy assessment (odds ratio, 3.22; 95% confidence interval, 2.4-4.3; P < .05). ConclusionThe implementation of the beta-lactam allergy clinical guideline resulted in most patients’ allergy labels being removed or advantageously updated. These allergy label changes correlated with a substantial increase in the percentage of beta-lactam antibiotics prescribed. After guideline implementation, beta-lactam antibiotics had a 3-fold increased odds of being prescribed independent of allergy label outcome.