Is Trough Concentration of Vancomycin Predictive of the Area Under the Curve? A Clinical Study in Elderly Patients

Background: Current guidelines suggest that vancomycin trough concentrations (Cmin) between 15 and 20 mg/L should be achieved to optimize vancomycin exposure and effect. The objective of this study was to analyze the correlation between vancomycin Cmin and the area under the concentration-time curve (AUC) and assess the ability to predict an AUC target of 400 mg.h/L based on Cmin. Methods: A retrospective analysis of vancomycin therapeutic drug monitoring data collected in 95 elderly patients treated with intermittent intravenous vancomycin was performed. For each patient, individual pharmacokinetic parameters of vancomycin and AUC(24) were estimated from concentration measurements using a Bayesian approach. The relationship between vancomycin Cmin and AUC was studied using global and local correlation analysis as well as logistic regression with Receiver Operating Characteristic curve analysis. Results: The overall correlation between AUC(24) and Cmin was significant but moderate (R-2 = 0.51). When vancomycin Cmin was greater than 15 mg/L, the corresponding AUC(24) was >400 mg.h/L in 95% of cases. However, AUC(24) values > 400 mg.h/L were obtained with Cmin < 15 mg/L in more than 30% of the cases. The logistic regression analysis identified a Cmin value of 10.8 mg/L as the optimal predictor of AUC(24) > 400 mg$ h/L. Conclusions: The results of this study indicate that the recommended target range of 15-20 mg/L for vancomycin Cmin seems acceptable for controlling vancomycin exposure, although a value of approximately 11 mg/L appears to be optimal and may be safer.