PROJECT SUMMARY The 1.2 million people in the United States affected by hematologic malignancy (HM) each year are at high risk of infection-related complications and mortality. As a result, HM patients are exposed to prolonged antibiotic therapy, and are at increased risk of harm from multidrug resistant organisms and antibiotic- associated adverse events. Optimizing selection of antibiotics in this population is a critical antibiotic stewardship (AS) goal. A major barrier to achieving this goal is inaccurate antibiotic allergy labels. Although self-reported beta-lactam (BL) allergy is found in up to 20% of all inpatients, 90% of patients with a reported penicillin (PCN) allergy are able to tolerate PCN. Inaccurate allergy labels may result in patients receiving sub-optimal antibiotic therapy with less effective, overly broad, and/or more toxic agents. In HM patients, BLs are preferred for many infectious complications. BL allergy is common in HM patients (>25%) and those with BL allergy have significantly greater hospital LOS, 30-day mortality, and antibiotic exposure. Studies of antibiotic allergy delabeling interventions combining history, skin testing and oral challenge in general hospitalized patients have shown that up to 85-95% of patients with reported BL allergy can be safely delabeled. Patients who are successfully delabeled have increased appropriate antibiotic use and improved clinical outcomes. Despite their increased risk of antibiotic-associated harm, cancer patients with BL allergy have not been prioritized in research on delabeling interventions. Although recent studies (including our own) provide promising early evidence for the feasibility of BL delabeling in cancer populations, the impact of a BL allergy delabeling intervention on clinical outcomes in the HM population is unstudied. Our long-term goal is to optimize antibiotic use and improve clinical outcomes in high-risk immunocompromised patients. The overall objective in this application is to test the impact of a pharmacist-led BL allergy delabeling intervention (Allergy Delabeling in Antibiotic Stewardship – “RENEW”) on clinical outcomes and antibiotic use in hospitalized patients with HM while concurrently assessing social and behavioral factors that shape implementation. The Specific Aims of this study are: Aim 1: Assess the Impact of the RENEW Intervention: To assess the impact of a BL allergy delabeling intervention on antibiotic use and clinical outcomes in HM patients using a cohort study design. Aim 2: Identify Barriers and Facilitators to Implementation of the RENEW Intervention: To identify barriers and facilitators to the implementation of the RENEW intervention via a concurrent mixed-methods process evaluation that will elicit the perceptions of patients and clinicians toward the intervention. This study will generate robust evidence to support broad dissemination of our findings to the HM population, inform subsequent interventions targeting high-risk ...