Introduction of a Penicillin Allergy De-Labelling Program with Direct Oral Challenge is Associated with Increased Downstream Utilization of Beta-Lactam Antimicrobials: A Multicenter Parallel Cohort Study with Crossover Evaluation

ABSTRACT Background Penicillin allergy labels are common and are often inaccurate. These labels can lead to unnecessary use of second-line non-beta-lactam antibiotics, and worse clinical outcomes. Objectives We measured the impact of the introducing of a standardized proactive penicillin allergy de-labelling program with oral amoxicillin challenge on subsequent antibiotic use. Methods We performed a retrospective comparison of parallel cohorts from two separate tertiary care hospital campuses across two penicillin de-labelling intervention periods. Outcomes included data including penicillin allergy label and antibiotic use, were collected for the index admission and the subsequent 6-month period. Descriptive statistics as well as multivariate regression analyses were performed. Results A total of 368 patients with penicillin allergy label were included across two campuses and study periods. 24 (13.8%) patients in the intervention group sustained penicillin allergy label at 30 days from admission vs. 3 (1.5%) in the non-intervention group (p < 0.001). In the 6-months following admission, beta-lactams were prescribed more frequently in the intervention groups vs. the non-intervention groups for all patients (28 [16.1%] vs 15 [7.7%], p= 0.04) and for only those patients who received antibiotics (28/46 [60.9%] vs. 15/40 [37.5%], p=0.097). In a multivariate analysis, the intervention was found to be associated with an increased odds of beta-lactam prescribing in all patients (OR 2.49, 95% CU 1.29-5.02) and in those prescribed at least one antibiotic (OR 2.44, 95% CI 1.00-6.15). There were no differences in overall antibiotic prescribing by intervention and non-intervention group during admission (113 [64.9%] vs. 112 [57.7%]) or within 6-months (46 [26.4%] vs. 40 [20.6%]). No drug related adverse events were reported. Conclusions Proactive penicillin allergy de-labelling for inpatients was associated with a reduced number of penicillin allergy labels and increased utilization of beta-lactam vs. other antibiotics in the subsequent 6-months. Capsule Summary A proactive systematic approach to antibiotic allergy de-labelling for inpatients with penicillin allergy label results in an increased number of patients de-labelled at hospital discharge and increased beta-lactam use in the subsequent 6 months.