The Influence of a Therapeutic Drug Monitoring Service on Vancomycin-Associated Nephrotoxicity

Abstract

Vancomycin's widespread use as the mainstay antibiotic against methicillin-resistant Staphylococcus aureus infections is complicated by its narrow therapeutic index. Therapeutic drug monitoring using area under the concentration-time curve (AUC)-guided dosing is recommended to optimize therapy and prevent vancomycin-associated nephrotoxicity (VAN). In 2018, a consultative therapeutic drug monitoring Advisory Service (the Service) was piloted at an Australian hospital to enable AUC-guided vancomycin dosing. This study sought to compare the incidence of VAN pre- and post-Service implementation. A 4-year retrospective observational study of intravenous vancomycin therapy (greater than 48 hours) in adults (aged 18 years or older), spanning 3 years before and 1-year after implementation of the Service was undertaken. Nephrotoxicity was defined as an increase in serum creatinine concentrations of 26.5 μmol/L or greater or 50% or more from baseline, on 2 or more consecutive days. Univariate analysis was performed to compare patients before and after implementation, and with and without VAN. Independent factors associated with VAN were identified using a multivariate model. In total, 971 courses of vancomycin therapy, administered to 781 patients, were included: 764 courses (603 patients) before implementation and 207 courses (163 patients) after implementation. The incidence of VAN decreased by 5% after Service implementation (15% before implementation vs 10% after implementation; P = .075). Independent factors associated with VAN were sepsis, heart failure, solid-organ transplant, concomitant piperacillin-tazobactam, and average vancomycin AUC during therapy. In conclusion, there was a nonsignificant trend toward a reduced incidence of VAN after the Service. Larger prospective studies are needed to confirm the efficacy of the Service.

Keywords: acute kidney injury; antibiotic stewardship; nephrotoxicity; patient safety; therapeutic drug monitoring; vancomycin.