Relationship between nephrotoxicity and area under the concentration–time curve of vancomycin in critically ill patients: a multicenter retrospective study

Abstract

ABSTRACT We aimed to assess the frequency of acute kidney injury (AKI) in different areas under the concentration–time curve (AUC) values of vancomycin (VAN) using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. This multicenter retrospective observational study was conducted in eight hospitals. We retrospectively analyzed the data of patients who had received VAN in an intensive care unit (ICU) between January 2020 and December 2022. The primary outcome was the incidence of AKI. Patients were classified into three groups according to the AUC24–48h at the initial therapeutic drug monitoring (TDM) as follows: <500, 500–600, and ≥600 µg·h/mL. The AUC24–48h values were calculated using the Bayesian estimation software Practical AUC-guided TDM. Among 146 patients [median age (interquartile range), 67 (56–78) years; 39% women], the AUC24–48h <500 µg·h/mL had an AKI rate of 6.5% (7/107), the AUC24–48h 500–600 µg·h/mL had an AKI rate of 28.0% (7/25), and the AUC24–48h ≥600 µg·h/mL had an AKI rate of 42.9% (6/14). In multivariate Cox proportional hazard analysis, the AUC24–48h 500–600 µg·h/mL [hazard ratio 5.4, 95% confidence interval (CI) 1.64–17.63] and the AUC24–48h ≥600 μg·h/mL (hazard ratio 7.0, 95% CI 2.31–21.18) significantly correlated with a higher incidence of AKI compared with the AUC24-48h <500 μg·h/mL. In conclusion, we identified an association between AUC on day 2 and the risk of AKI in ICU patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI.IMPORTANCEVancomycin (VAN) is a glycopeptide antibiotic and one of the most commonly used antibiotics for severe infections caused by methicillin-resistant Staphylococcus aureus. However, higher VAN concentrations have been associated with an increased risk of acute kidney injury (AKI). Herein, we aimed to assess the frequency of AKI in different areas under the concentration–time curve (AUC) values of VAN using a two-point blood collection method, allowing for accurate AUC assessment in critically ill patients. We identified an association between AUC on day 2 and the risk of AKI in intensive care unit patients, suggesting that not only AUCs above 600 µg·h/mL but also those between 500 and 600 µg·h/mL pose a risk for AKI. Therefore, individualized dosing is feasible, with pharmacists being able to optimize VAN doses to attain appropriate targets.

Keywords

• vancomycin
• therapeutic drug monitoring
• nephrotoxicity
• area under the concentration–time curve