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万古霉素持续输注的剂量和暴露:一项回顾性研究。

Dosing and Exposure of Vancomycin With Continuous Infusion: A Retrospective Study.

机构信息

Department of Pharmacy, Radboudumc, Nijmegen, The Netherlands.

出版信息

Clin Pharmacol Ther. 2024 Sep;116(3):665-669. doi: 10.1002/cpt.3221. Epub 2024 Feb 26.

DOI:10.1002/cpt.3221
PMID:38409960
Abstract

Vancomycin continuous infusion (CI) has suggested benefits over intermittent infusion: reduced nephrotoxicity, higher target attainment, and simpler therapeutic drug monitoring (TDM). Empiric dosing regimens range from 30-60 mg/kg/day and it is unclear which regimen results in optimal exposure. This study evaluates whether a dosing regimen of 45 mg/kg/day after a 20 mg/kg loading dose for patients with estimated glomerular filtration rate (eGFR) ≥ 50 mL/min results in adequate exposure. We retrospectively analyzed plasma concentrations from patients treated with vancomycin CI as routine clinical care between February and October 2021. Patients under 18 years old, with renal replacement therapy, reduced creatinine clearance (Chronic Kidney Disease Epidemiology Collaboration < 50 mL min/1.73 m) or outpatient antibiotic therapy were excluded. Dose, renal function, and blood draw procedures were assessed for each measured vancomycin sample. Initially, 121 samples were included. Subsequently, 7 samples, 6 of which with concentrations ≥ 40 mg/L, were verified to be incorrectly drawn and excluded. With doses of 40-50 mg/kg/day concentrations ranged from 18.4-61.0 mg/L. Only 25% were within the target window of 17-25 mg/L and 15% were ≥ 40 mg/L. Supratherapeutic concentrations were observed in 89% of samples from patients dosed 40-60 mg/kg/day with eGFR 50-80 mL/min. Concluding, an empiric dosing regimen of 45 mg/kg results in too high vancomycin exposure and thus we recommend lower doses and differentiation according to renal function. Additionally, when measuring concentrations over 40 mg/L incorrect sampling must be excluded before dose adjustment and the large variability in exposure between patients, warrants the need for swift TDM.

摘要

万古霉素持续输注(CI)相较于间歇性输注具有优势:降低肾毒性、更高的靶目标实现率和更简单的治疗药物监测(TDM)。经验性给药方案的范围为 30-60mg/kg/天,目前尚不清楚哪种方案能获得最佳的暴露量。本研究评估了对于肾小球滤过率(eGFR)≥50mL/min 的患者,在给予 20mg/kg 负荷剂量后,采用 45mg/kg/天的剂量方案是否能获得足够的暴露量。我们回顾性分析了 2021 年 2 月至 10 月期间作为常规临床护理接受万古霉素 CI 治疗的患者的血浆浓度。排除年龄小于 18 岁、接受肾脏替代治疗、肌酐清除率降低(慢性肾脏病流行病学合作研究<50mL/min/1.73m)或门诊抗生素治疗的患者。评估了每个测量的万古霉素样本的剂量、肾功能和采血程序。最初纳入了 121 个样本。随后,有 7 个样本(其中 6 个浓度≥40mg/L)被证实为错误采血,被排除在外。剂量为 40-50mg/kg/天时,浓度范围为 18.4-61.0mg/L。仅有 25%的样本浓度处于 17-25mg/L 的目标窗内,15%的样本浓度≥40mg/L。在 eGFR 为 50-80mL/min 的患者中,89%的患者接受 40-60mg/kg/天的剂量时,观察到超治疗浓度。结论,经验性的 45mg/kg 剂量方案会导致万古霉素暴露量过高,因此我们建议根据肾功能降低剂量并进行区分。此外,当测量浓度超过 40mg/L 时,在调整剂量之前必须排除错误采样,并且患者之间的暴露量存在很大的差异,这需要快速进行 TDM。

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