Is Trough Concentration of Vancomycin Predictive of the Area Under the Curve? A Clinical Study in Elderly Patients
Anis Bel Kamel, Laurent Bourguignon, M A Gómez Marcos, Michel Ducher, Sylvain Goutelle
Abstract
Anis Bel Kamel, Laurent Bourguignon, M A Gómez Marcos, Michel Ducher, Sylvain Goutelle
Abstract
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 AUC24 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 AUC24 and Cmin was significant but moderate (R = 0.51). When vancomycin Cmin was greater than 15 mg/L, the corresponding AUC24 was >400 mg·h/L in 95% of cases. However, AUC24 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 AUC24 > 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.
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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 AUC24 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 AUC24 and Cmin was significant but moderate (R = 0.51). When vancomycin Cmin was greater than 15 mg/L, the corresponding AUC24 was >400 mg·h/L in 95% of cases. However, AUC24 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 AUC24 > 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.
Key concepts: Cmin, Vancomycin, Medicine, Area under the curve, Therapeutic drug monitoring, Receiver operating characteristic, Logistic regression, Predictive value