BACKGROUND: Vancomycin guidelines recommend area-under-the-curve (AUC) therapeutic monitoring for patients with severe methicillin-resistant Staphylococcus aureus (MRSA) infections. No recommendations exist for patients with non-severe staphylococcal infections or those with other Gram-positive infections. AUC-based vancomycin dosing can be resource-intensive and may not be necessary for all patients. METHODS: New institutional guidelines for vancomycin dosing were implemented across an eight-hospital health system in 2023. The new guidelines recommended either AUC or trough-based dosing depending on the severity of the infection and the likelihood of MRSA. Adult patient encounters with at least one vancomycin administration were compared retrospectively 6 months pre-implementation and 6 months post-implementation. Cumulative vancomycin dose, administrations, and serum levels were assessed. The rate of acute kidney injury (AKI) was compared in a subgroup of patient encounters with four or more administrations. Pharmacist time saved using a blended approach compared to a uniform AUC dosing guideline was estimated based on the number of patients receiving trough-based dosing in the post-implementation group. RESULTS: A total of 8155 patient encounters were included in the analysis (3916 pre-implementation, 4239 post-implementation). The primary outcome of median cumulative vancomycin dose (mg) was 500 mg lower in the post-implementation group (3000 mg pre-implementation vs 2500 mg post-implementation, Odds ratio [OR] 0.94 95% confidence interval [CI] 0.90-0.97, p <
0.002). Patients in the post-implementation group were significantly less likely to have vancomycin serum levels drawn (OR 0.86
95% CI 0.78, 0.96, p = 0.005). A subgroup of patient encounters receiving four or more vancomycin administrations included 2483 patient encounters (1251 pre-implementation, 1232 post-implementation). AKI occurred in 120 (9.6%) cases pre-implementation and 89 (7.2%) cases post-implementation. The risk of AKI was significantly lower post-implementation (OR 0.73
95% CI 0.55, 0.98, p = 0.038). Estimated pharmacist time saved was between 2229 to 5201 min, equating to an estimated 6,851.24 to 9,319.56 saved over 6 months, with blended vancomycin dosing. CONCLUSION: In this large multi-hospital cohort, the implementation of a blended dosing method using a majority of AUC-based dosing reduced cumulative vancomycin doses, serum levels, and AKI. Including trough recommendations for patients with less severe infections and non-MRSA, Gram-positive pathogens may have saved significant pharmacist time and associated costs compared to a uniform AUC dosing policy. This study further highlights the sizeable amount of unnecessary vancomycin use with a corresponding low incidence of severe MRSA infections.