Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8560, Japan.
Hospital Pharmacy, Nagoya University Graduate School of Medicine, Nagoya, Aichi, 466-8560, Japan.
J Pharmacol Sci. 2022 Apr;148(4):358-363. doi: 10.1016/j.jphs.2022.02.005. Epub 2022 Feb 20.
Vancomycin is a glycopeptide antibiotic that is a primary treatment for methicillin-resistant Staphylococcus aureus infections. To enhance its clinical effectiveness and prevent nephrotoxicity, therapeutic drug monitoring (TDM) of trough concentrations is recommended. Initial vancomycin dosing regimens are determined based on patient characteristics such as age, body weight, and renal function, and dosing strategies to achieve therapeutic concentration windows at initial TDM have been extensively studied. Although numerous dosing nomograms for specific populations have been developed, no comprehensive strategy exists for individually tailoring initial dosing regimens; therefore, decision making regarding initial dosing largely depends on each clinician's experience and expertise. In this study, we applied a machine-learning (ML) approach to integrate clinician knowledge into a predictive model for initial vancomycin dosing. A dataset of vancomycin initial dose plans defined by pharmacists experienced in vancomycin TDM (i.e., experts) was used to build the ML model. Although small training sets were used, we established a predictive model with a target attainment rate comparable to those of experts, another ML model, and commonly used vancomycin dosing software. Our strategy will help develop an expert-like predictive model that aids in decision making for initial vancomycin dosing, particularly in settings where dose planning consultations are unavailable.
万古霉素是一种糖肽类抗生素,是治疗耐甲氧西林金黄色葡萄球菌感染的主要药物。为了提高其临床疗效并预防肾毒性,建议进行谷浓度治疗药物监测(TDM)。初始万古霉素给药方案根据患者的年龄、体重和肾功能等特征确定,并且已经广泛研究了初始 TDM 时达到治疗浓度范围的给药策略。尽管已经为特定人群制定了许多剂量图表,但没有针对个体化初始给药方案的综合策略;因此,初始给药的决策在很大程度上取决于每个临床医生的经验和专业知识。在这项研究中,我们应用机器学习(ML)方法将临床医生的知识整合到初始万古霉素给药的预测模型中。该 ML 模型使用了由在万古霉素 TDM 方面经验丰富的药剂师(即专家)定义的万古霉素初始剂量计划数据集进行构建。尽管使用了较小的训练集,但我们建立的预测模型的目标达成率与专家、另一个 ML 模型和常用的万古霉素给药软件相当。我们的策略将有助于开发出类似专家的预测模型,为初始万古霉素给药的决策提供帮助,特别是在无法进行剂量规划咨询的情况下。