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

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 <mu>g<middle dot>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 <mu>g<middle dot>h/mL had an AKI rate of 6.5% (7/107), the AUC24-48h 500-600 mu g<middle dot>h/mL had an AKI rate of 28.0% (7/25), and the AUC24-48h >= 600 mu g<middle dot>h/mL had an AKI rate of 42.9% (6/14). In multivariate Cox proportional hazard analysis, the AUC24-48h 500-600 mu g<middle dot>h/mL [hazard ratio 5.4, 95% confidence interval (CI) 1.64-17.63] and the AUC24-48h >= 600 mu g<middle dot>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 mu g<middle dot>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 mu g<middle dot>h/mL but also those between 500 and 600 mu g<middle dot>h/mL pose a risk for AKI.