Interventions to optimize duration of antibiotic therapy and encourage oral transition for uncomplicated gram-negative blood stream infections across a health system

Background: Shorter antibiotic courses and transition to oral therapy for uncomplicated gram-negative bloodstream infections (GN-BSI) are evidence-supported yet remain challenging to implement. Here we report our experience with a GN-BSI antimicrobial stewardship (AS) quality improvement initiative in a large health system. Methods: We implemented two sequential AS interventions in adult patients hospitalized with uncomplicated GN-BSI: (1) mandatory AS review of patients discharging on intravenous (IV) antibiotics (“OPAT review”) and (2) a clinical guideline informing oral antibiotic transition and duration, in our 22-hospital system. We evaluated the initiative from January 2018 to September 2024. Pre- and postimplementation rates of (1) IV antibiotics at discharge and (2) total length of antibiotic therapy were calculated across the following periods: preintervention, after OPAT review, and after guideline implementation. Secondary outcomes included duration <10 days, oral antibiotic prescribing, and guideline-recommended dosing. Results: 3,231 patients (preintervention: 666, postOPAT review: 1,357, postguideline: 1,208) were included. We observed decreases in IV antibiotics at discharge (22.7% preintervention, 10.7% postOPAT review, and 9.2% postguideline, p < 0.001) and median length of treatment (13.5 days preintervention to 10.7 days postguideline, p < 0.001). We also observed improvement in durations <10 days (19.1% vs 45%, p < 0.001), oral antibiotic prescriptions, and appropriate dosing (2.8% vs 33.5%, p < 0.001), but no difference in rates of BSI recurrence, mortality, or C. difficile infection. Conclusion: After implementing GN-BSI-focused AS initiatives in our large health system, we observed a shift toward more frequent oral rather than IV antibiotics at discharge, and shorter overall antibiotic durations, without obvious changes in adverse outcomes.