Abstract
BackgroundThe standard dose of vancomycin (VCM, 2 g/day) sometimes fails to achieve therapeutic concentration in patients with normal renal function. In this study, we aimed to identify factors to predict patients who require high-dose vancomycin (> 2 g/day) to achieve a therapeutic concentration and to develop a decision flowchart to select these patients prior to VCM administration.MethodsPatients who had an estimated creatinine clearance using the Cockcroft–Gault equation (eCCr) of ≥50 mL/min and received intravenous VCM were divided into 2 cohorts: an estimation set (n = 146, from April to September 2016) and a validation set (n = 126, from October 2016 to March 2017). In each set, patients requiring ≤2 g/day of VCM to maintain the therapeutic trough concentration (10–20 μg/mL) were defined as standard-dose patients, while those who needed > 2 g/day were defined as high-dose patients. Univariate and multivariate logistic regression analysis was performed to identify the predictive factors for high-dose patients and decision tree analysis was performed to develop decision flowchart to identify high-dose patients.ResultsAmong the covariates analyzed, age and eCCr were identified as independent predictors for high-dose patients. Further, the decision tree analysis revealed that eCCr (cut off value = 81.3 mL/min) is the top predictive factor and is followed by age (cut off value = 58 years). Based on these findings, a decision flowchart was constructed, in which patients with eCCr ≥81.3 mL/min and age < 58 years were designated as high-dose patients and other patients were designated as standard-dose patients. Subsequently, we applied this decision flowchart to the validation set and obtained good predictive performance (positive and negative predictive values are 77.6 and 84.4%, respectively).ConclusionThese results suggest that the decision flowchart constructed in this study provides an important contribution for avoiding underdosing of VCM in patients with eCCr of ≥50 mL/min.
Highlights
The standard dose of vancomycin (VCM, 2 g/day) sometimes fails to achieve therapeutic concentration in patients with normal renal function
Because numerous number of reports have shown that the ratio of the area under the drug concentration–time curve over 24 h (AUC24, μg∙h/mL) to the minimum inhibitory concentration of pathogens (MIC, μg/mL), hereafter referred to as AUC24/MIC, is the best pharmacokinetic/pharmacodynamic (PK/PD) index to predict the clinical efficacy of VCM [2, 3], the latest Infectious Diseases Society of America (IDSA) guidelines [4] strongly recommends AUC-guided dosing to achieve an AUC24/MIC of 400–600 in place of conventional trough concentration (Ctrough)-guided dosing
The exclusion criteria were defined as follows: (A) patients under 18 years of age, (B) first Ctrough was measured within 2 days from the start of VCM administration [18, 22, 23], (C) VCM dosage was changed before the first Ctrough measurement, and (D) renal function that fluctuated during VCM treatment
Summary
The standard dose of vancomycin (VCM, 2 g/day) sometimes fails to achieve therapeutic concentration in patients with normal renal function. Because numerous number of reports have shown that the ratio of the area under the drug concentration–time curve over 24 h (AUC24, μg∙h/mL) to the minimum inhibitory concentration of pathogens (MIC, μg/mL), hereafter referred to as AUC24/MIC, is the best pharmacokinetic/pharmacodynamic (PK/PD) index to predict the clinical efficacy of VCM [2, 3], the latest Infectious Diseases Society of America (IDSA) guidelines [4] strongly recommends AUC-guided dosing to achieve an AUC24/MIC of 400–600 in place of conventional trough concentration (Ctrough)-guided dosing It is sometimes time and cost consuming process to calculate AUC24 because it requires multiple blood sampling and pharmacokinetic analysis using dedicated software. Considering these reports, to achieve Ctrough of 10–20 μg/mL would maintain certain clinical significance in the era of AUCguided dosing
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