Area-Under-Curve–Guided Versus Trough-Guided Monitoring of Vancomycin and Its Impact on Nephrotoxicity: A Systematic Review and Meta-Analysis

Abstract

Background: Conventionally, vancomycin trough levels have been used for therapeutic drug monitoring (TDM). Owing to the increasing evidence of trough levels being poor surrogates of area under the curve (AUC) and the advent of advanced pharmacokinetics software, a paradigm shift has been made toward AUC-guided dosing. This study aims to evaluate the impact of AUC-guided versus trough-guided TDM on vancomycin-associated nephrotoxicity.Methods: A systematic review was conducted using PubMed, Embase, Web of Science, Cumulative Index to Nursing and Allied Health Literature, Google scholar, and Cochrane library databases; articles published from January 01, 2009, to January 01, 2021, were retrieved and reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Studies that evaluated trough-guided or AUC-guided vancomycin TDM and vancomycin-associated nephrotoxicity were included. Randomeffects models were used to compare the differences in nephrotoxicity.Results: Of the 1191 retrieved studies, 57 were included. Most studies included adults and older adults (n = 47, 82.45%). The pooled prevalence of nephrotoxicity was lower in AUC-guided TDM [6.2%; 95% confidence interval (CI): 2.9%-9.5%] than in trough-guided TDM (17.0%; 95% CI: 14.7%-19.2%). Compared with the trough-guided approach, the AUC-guided approach had a lower risk of nephrotoxicity (odds ratio: 0.53; 95% CI: 0.32-0.89). The risk of nephrotoxicity was unaffected by the AUC derivation method. AUC thresholds correlated with nephrotoxicity only within the first 96 hours of therapy. Conclusions:The AUC-guided approach had a lower risk of nephrotoxicity, supporting the updated American Society of Health-System Pharmacists guidelines. Further studies are needed to evaluate the optimal AUC-derivation methods and clinical utility of repeated measurements of the AUC and trough levels of vancomycin.

Prolonged versus intermittent vancomycin infusion in critically ill patients with sepsis: A systematic review and meta-analysis

“…The latest Infectious Diseases Society of America guidelines [4] recommend an AUC/MIC of 400-600 for vancomycin. Trough-guided therapy may signi cantly exceed the target AUC, and an AUC-guided approach has a lower risk of nephrotoxicity [33].…”

Risk Factor Analysis of Vancomycin-Induced Nephrotoxicity in Paediatric Patients Aged 0–1 Year Using Japanese Medical Database

“…15,17) Of the 57 studies (including 8 paediatric studies) included in a recent meta-analysis, 34 (including 3 paediatric studies) used the IDSA 2009 guidelines as their criterion for determining nephrotoxicity. 18) As per Criterion 2, all patients' Scr values were checked throughout VCM administration according to the Kidney Disease Improving Global Outcomes (KDIGO) criteria, 19) and cases with an increase of more than 0.3 mg/dL within 48 h or more than 1.5-fold within 7 d were judged to have VIN. The KDIGO criteria are presented in IDSA's 2020 guidelines as a method for defining VIN.…”

Therapeutic drug monitoring of glycopeptide antimicrobials: An overview of liquid chromatography-tandem mass spectrometry methods

“…Vancomycin falls under the category of time-dependent antimicrobials. An AUC-based TDM approach has recently been recommended as opposed to solely monitoring C trough levels to ensure the achievement of a PK/PD target of AUC 0-24h /MIC > 400–600 and reduce acute kidney injury rates [6] , [38] , [39] , [40] , [41] , [42] , [43] , [44] , [45] .…”