Evaluation of Vancomycin Therapeutic Drug Monitoring Strategies: Pharmacokinetic, Pharmacogenetic, and Clinical Perspectives in a Prospective, Real-World Cohort Study

Abstract Purpose Vancomycin therapeutic drug monitoring is essential for optimizing efficacy and reducing the risk of vancomycin-associated acute kidney injury (VA-AKI). Although recent guidelines recommend the ratio of area under the curve over 24 h to minimum inhibitory concentration (AUC 24 /MIC)–based monitoring over trough concentration-based monitoring, differences between AUC 24 /MIC estimation methods (e.g., pharmacokinetic equations and Bayesian approaches) may influence therapeutic classification in clinical practice. In addition, pharmacogenetic factors contributing to interindividual variability in vancomycin exposure remain incompletely characterized. Methods This prospective, single-center cohort study included adult patients who received intravenous vancomycin for at least 72 h between June 2024 and April 2025. Vancomycin trough and peak plasma concentrations were measured using an enzyme-linked immunosorbent assay. AUC 24 /MIC values were calculated using pharmacokinetic equation and Bayesian method. Agreement in therapeutic classification between trough concentration–based and AUC 24 /MIC-based monitoring was assessed. Associations between the rs2789047 genetic variant and relevant parameters were also evaluated. Results Thirty-six patients were included, of whom 38.9% developed VA-AKI. Despite strong correlations between trough concentration and AUC 24 /MIC values ( r = 0.84–0.87), substantial discordance in therapeutic classification was observed, with agreement rates of 63.9% for pharmacokinetic equation-based and 66.7% for Bayesian-based compared with trough concentration-based monitoring. In contrast, pharmacokinetic equation-based and Bayesian-based methods demonstrated strong concordance (86.1%). Higher trough concentrations and AUC 24 /MIC values were significantly associated with VA-AKI ( p < 0.001). Carriers of rs2789047 A-allele exhibited higher trough concentrations and reduced elimination rates. Conclusion Trough concentration-based monitoring frequently misclassified vancomycin exposure compared with AUC 24 /MIC–based approaches. Pharmacogenetic variability may further influence vancomycin exposure.