Flowchart for predicting achieving the target area under the concentration-time curve of vancomycin in critically ill Japanese patients: A multicenter retrospective study

Abstract

Introduction: In therapeutic drug monitoring (TDM) of vancomycin (VCM), the area under the concentration-time curve (AUC) is related to the clinical efficacy and toxicity. Therefore, herein, we examined the factors associated with achieving the target AUC at follow-up and developed a decision flowchart for achieving the target AUC in critically ill patients.

Methods: This multicenter retrospective observational study was conducted at eight hospitals. We retrospectively analyzed data from patients who had received VCM in the intensive care unit from January 2020 to December 2022. Decision-tree (DT) analysis was performed using factors with p < 0.1 in univariate analysis as the independent variables. Case data were split up to two times, and four subgroups were included. The primary endpoint was achieving the target AUC at the follow-up TDM (AUC_follow-up) and target AUC_follow-up achievement was defined as an AUC of 400-600 μg‧h/mL. The initial AUC values were calculated with the 2-point concentrations (peak and trough) using the Bayesian estimation software Practical AUC-guided TDM (PAT).

Results: Among 70 patients (median age [interquartile range], 66 [56, 79] years; 50 % women), the AUC_follow-up was achieved in 70 % (49/70). Three factors were selected for the decision flow chart: predicted AUC_follow-up of 400-600 μg‧h/mL, dosing at 12-h intervals, and CCr of 130 mL/min/1.73 m² or higher; the accuracy was adequate (92 %, R² 0.52).

Conclusion: We successfully identified the factors associated with achieving the target AUC of VCM at follow-up TDM and developed a simple-to-use DT model. However, the validity of the findings needs to be evaluated.

Keywords: Area under the concentration-time curve; Decision-tree analysis; Therapeutic drug monitoring; Vancomycin.