1097. A Comparison of Area-Under Curve (AUC)-Guided vs Trough-Guided Monitoring of Vancomycin and Its Impact on Nephrotoxicity: A Systematic Review and Meta-analysis

Abstract

Background Trough levels have been used for Vancomycin (VAN) therapeutic drug monitoring (TDM) historically due to its practicality. A paradigm shift towards the use of area under curve (AUC)-guided dosing TDM has been made due to availability of advanced pharmacokinetics software, variability between trough levels and AUC values and the potential for reducing toxicity. This review aims to evaluate the impact of AUC-guided vs trough-guided vancomycin TDM on nephrotoxicity-related outcomes. Methods A systematic review was conducted using PubMed®, Embase®, Web of Science®, CINAHL®, Google scholar and Cochrane library® up till 1st January 2021 and was reported according to the PRISMA checklist. Studies which evaluated AUC-guided or trough-guided VAN TDM and vancomycin-associated nephrotoxicity were included. Random effects models were used to compare differences in nephrotoxicity between trough level or AUC based vancomycin TDM due to expected heterogeneity in study designs. PRISMA Flowchart PRISMA flow chart depicting the selection process of studies included in the meta-analysis Results Of 1191 records retrieved, 57 studies were included. Majority of studies included adult and elderly patients (n=47, 82.5%). The pooled prevalence of nephrotoxicity was lower using the AUC-guided TDM [6.2%, 95% confidence interval (CI): 2.9 – 9.5%] compared to trough-guided TDM [17.0%; 95% CI: 14.7 – 19.2%]. The risk of nephrotoxicity was lower with the AUC-guided approach as compared with the trough-guided approach [OR: 0.53, 95% CI: 0.32–0.89]. AUC thresholds correlated with risk of nephrotoxicity only for the first 96 hours of therapy. A frequency analysis of significant multivariable factors showed that concomitant use of nephrotoxins, VAN trough levels and duration of VAN therapy were most commonly associated with nephrotoxicity. Forest plot comparing the risk of nephrotoxicity of AUC-guided vs trough-guided Forest plot comparing the risk of nephrotoxicity of AUC-guided vs trough-guided Pooled nephrotoxicity rates from AUC-guided monitoring Pooled nephrotoxicity rates from AUC-guided monitoring Pooled nephrotoxicity rates from trough-guided monitoring Pooled nephrotoxicity rates from trough-guided monitoring Conclusion The AUC-guided approach appeared to have lower risk of nephrotoxicity which supports the updated American Society of Health-System Pharmacists recommendations. More studies should be performed to evaluate the optimal derivation of AUC and clinical utility of repeated measurements of vancomycin AUC and trough levels. Disclosures All Authors: No reported disclosures

A Quasi-Experimental Evaluation of Single Trough-Based Area Under the Curve Guided Dosing on the Incidence of Vancomycin Associated Nephrotoxicity in Veteran Patients

“…In addition, AUC thresholds correlated with nephrotoxicity risk only for the first 96 hours suggesting that factors beyond vancomycin use likely associated with longer LOS may impact the incidence of nephrotoxicity. 27 Our study observed similar trends. Tsutsuura et al performed a meta-analysis of 16 studies to explore the relationship between trough concentrations and AKI incidence and showed significant risk of AKI with trough concentrations >20 mg/mL.…”