在群体药代动力学模型切换后，万古霉素的靶点实现得到改善：一项大规模的精确给药准实验研究

摘要(中文译文)

本研究的目的是在19个医院系统的90 295例患者中，评估更换用于万古霉素模型引导精准给药（MIPD）的人群药代动力学模型对目标达成率、急性肾损伤发生率、给药剂量及采样负担的影响。我们采用中断时间序列模型，评估了更改默认万古霉素MIPD模型的站点在主要终点方面的变化，包括万古霉素浓度-时间曲线下面积（AUC）目标达成率、达标时间以及万古霉素相关AKI发生率。次要终点包括万古霉素给药剂量（第1天及整个疗程）和采样频率。未更换模型的医院系统作为对照。在BMI < 40 kg/m²的患者中，从Goti模型转换为Thomson模型显著改善了第1天（+2.1%，< 0.001）、第2天（+3.1%，< 0.001）以及整个治疗疗程（+2.7%，< 0.001）的AUC目标达成率。每疗程万古霉素采样次数（+0.06次/疗程，< 0.05）和达标时间（+0.26小时，< 0.05）出现小幅增加。AUC的改善未伴随AKI发生率的统计学显著增加（KDIGO 1期：+0.314%，> 0.05/3；2期：+0.347%，> 0.05/3；3期：+0.034%，> 0.05/3）。在BMI ≥ 40 kg/m²或对照队列中未观察到显著差异。这项大型准实验研究表明，从一对经过充分验证且预测性高的模型更换为另一对模型，可改善万古霉素目标达成率，同时维持较低的不良事件发生率。

Abstract

The aim of this study was to evaluate the impact of switching population pharmacokinetic models used for model-informed precision dosing (MIPD) of vancomycin on target attainment, acute kidney injury rates, dosing, and sampling burden in 90 295 patients across nineteen hospital systems. We assessed sites that changed their default vancomycin MIPD model on primary endpoints, including vancomycin area under the concentration-time curve (AUC) target attainment, time to target attainment, and vancomycin-associated AKI rates using an interrupted time series model. Secondary endpoints included vancomycin dosing (day 1 and total course) and sampling frequency. Hospital systems that did not change models served as controls. In BMI < 40 kg/m² patients, the Goti-to-Thomson model transition significantly improved AUC target attainment on day 1 (+2.1%, < 0.001), day 2 (+3.1%, < 0.001), and across the whole treatment course (+2.7%, < 0.001). Small increases occurred in vancomycin sampling per course (+0.06 samples/course, < 0.05) and time to target attainment (+0.26 hours, < 0.05). AUC improvements occurred without statistically significant increases in AKI incidence (KDIGO Stage 1: +0.314%, > 0.05/3; Stage 2: +0.347%, > 0.05/3, Stage 3: +0.034%, > 0.05/3). No significant differences were observed in the BMI ≥ 40 kg/m or control cohorts. This large quasi-experimental study shows that switching from one pair of well-validated and highly predictive models to another improves vancomycin target attainment while maintaining low adverse event rates.

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