Vancomycin-Induced Nephrotoxicity and Therapeutic Drug Monitoring: Current Insights and Clinical Management Strategies

Abstract

   ABSTRACT

Background: Vancomycin remains a cornerstone antimicrobial for the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections; however, vancomycin-associated acute kidney injury (VA-AKI) remains an important treatment-related complication, particularly among critically ill patients, individuals with obesity or pre-existing renal impairment, and those receiving concomitant nephrotoxic medications.

Objective: This narrative review synthesizes contemporary evidence on the epidemiology, pathophysiology, risk factors, diagnostic biomarkers, therapeutic drug monitoring (TDM), and clinical management of VA-AKI, with particular emphasis on developments in vancomycin exposure monitoring and individualized dosing.

Methods: A structured literature search of PubMed, Embase, and the Cochrane Library was conducted for relevant studies published predominantly between 2020 and 2026. Seminal earlier studies and major clinical guidelines were also considered where necessary to describe established pharmacokinetic, pharmacodynamic, and toxicodynamic concepts.

Key Findings: Current evidence supports a transition from trough-based monitoring toward area-under-the-concentration-time-curve (AUC)-guided dosing for serious MRSA infections. The 2020 ASHP/IDSA/PIDS/SIDP consensus guideline recommends targeting a 24-hour AUC to minimum inhibitory concentration ratio (AUC24/MIC) of 400–600 when an MIC of 1 mg/L is assumed. AUC-guided monitoring has generally been associated with lower nephrotoxicity than traditional trough-targeted strategies while maintaining therapeutic efficacy. Concomitant administration of vancomycin and piperacillin-tazobactam has also been associated with a higher incidence of AKI than combinations involving vancomycin with cefepime or meropenem, although the contribution of true structural kidney injury versus changes in creatinine handling remains an area of investigation. Emerging biomarkers, including urinary kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL), together with alternative renal function markers such as cystatin C, may permit earlier identification of kidney dysfunction than serum creatinine alone. Bayesian model-informed precision dosing provides an additional strategy for individualized AUC estimation using limited concentration sampling.

Conclusion: Contemporary strategies for reducing VA-AKI emphasize AUC-guided TDM, individualized assessment of nephrotoxicity risk, minimization of avoidable concomitant nephrotoxins, appropriate renal function monitoring, and timely dose adjustment or antimicrobial modification when kidney injury develops. Bayesian precision-dosing approaches and emerging kidney injury biomarkers may further improve individualized vancomycin management, although additional prospective validation is required in several patient populations.