Yamaguchi Ryo, Kani Hiroko, Yamamoto Takehito, Tanaka Takehiro, Suzuki Hiroshi
Department of Pharmacy, The University of Tokyo Hospital, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-8655, Japan.
The Education Center for Clinical Pharmacy, Graduate School of Pharmaceutical Sciences, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan.
J Pharm Health Care Sci. 2022 Jan 4;8(1):3. doi: 10.1186/s40780-021-00231-w.
The 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.
Patients 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.
Among 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).
These 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.
对于肾功能正常的患者,万古霉素(VCM)的标准剂量(2克/天)有时无法达到治疗浓度。在本研究中,我们旨在确定预测需要高剂量万古霉素(>2克/天)以达到治疗浓度的患者的因素,并制定一个决策流程图,以便在给予VCM之前选择这些患者。
使用Cockcroft-Gault方程估算肌酐清除率(eCCr)≥50毫升/分钟且接受静脉注射VCM的患者被分为两个队列:一个估算集(n = 146,2016年4月至9月)和一个验证集(n = 126,2016年10月至2017年3月)。在每个集合中,将需要≤2克/天的VCM以维持治疗谷浓度(10 - 20微克/毫升)的患者定义为标准剂量患者,而需要>2克/天的患者定义为高剂量患者。进行单因素和多因素逻辑回归分析以确定高剂量患者的预测因素,并进行决策树分析以制定识别高剂量患者的决策流程图。
在分析的协变量中,年龄和eCCr被确定为高剂量患者的独立预测因素。此外,决策树分析显示eCCr(截断值 = 81.3毫升/分钟)是首要预测因素,其次是年龄(截断值 = 58岁)。基于这些发现,构建了一个决策流程图,其中eCCr≥81.3毫升/分钟且年龄<58岁的患者被指定为高剂量患者,其他患者被指定为标准剂量患者。随后,我们将此决策流程图应用于验证集,获得了良好的预测性能(阳性和阴性预测值分别为77.6%和84.4%)。
这些结果表明,本研究构建的决策流程图为避免eCCr≥50毫升/分钟的患者VCM剂量不足做出了重要贡献。