Clinical validation of the two-point method for predicting vancomycin AUC based on peak and trough plasma concentrations

Abstract

Background: Vancomycin area under the curve/minimum inhibitory concentration (AUC/MIC) has been proposed as a therapeutic drug monitoring (TDM) target to dose vancomycin. It is time-consuming to estimate AUCs using traditional methods. A two-point trough-peak method is more straightforward for calculating the vancomycin AUC. However, the technique and the AUC/MIC target have not been validated in Chinese patients.

Aim: To compare the clinical outcomes of vancomycin therapy in Chinese older adults (aged > 60 years) between the trough-only and the two-point peak-trough AUC TDM approaches.

Method: The patients were divided into study and control groups according to TDM approaches. A trough-based TDM was used in the control group (target trough level 15-20 mg/L). Stanford University has provided a method to predict vancomycin AUC using peak-valley concentration alone (two-point method). A two-point trough-peak TDM approach was employed in the study group (target AUC/MIC ≥ 400). The effect of vancomycin was evaluated in terms of clinical findings, laboratory values, and bacteriologic responses. The effects of treatment and kidney functions were compared between the two groups.

Results: A total of 389 patients met the study inclusion criteria, and 189 were excluded based on the exclusion criteria. Of the 200 patients, 80 received the two-point TDM approach (the study group), and 120 were monitored using the trough-based approach (the control group). The average age was 69.8 ± 7.1 years. Staphylococcus aureus (34%) was the most common Gram-positive bacteria. No vancomycin-related nephrotoxicity was observed in either group. The percentages of patients with an excellent response to vancomycin therapy were significantly higher in the study group than in the control group, 90% (72/80) versus 73.3% (88/120), P = 0.0039.

Conclusion: The two-point peak-trough method is practical for obtaining vancomycin AUC. The AUC/MIC ≥ 400 target demonstrates treatment effectiveness and safety in older Chinese patients.

Keywords: Area under the curve; Chinese; Chinese older patients; Methicillin-resistant Staphylococcus aureus; Minimum inhibitory concentration; Pharmacokinetics; Therapeutic drug monitoring; Vancomycin.