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首页> 外文期刊>Antimicrobial agents and chemotherapy. >Reappraisal of Linezolid Dosing in Renal Impairment To Improve Safety
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Reappraisal of Linezolid Dosing in Renal Impairment To Improve Safety

机译：重新评估肾脏损伤中的线唑胺给药，提高安全性

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Linezolid is administered as a fixed dose to all patients despite evidence of increased exposure and myelosuppression in renal impairment. The objectives of these studies were to assess the risk of thrombocytopenia with standard-dose linezolid in renal impairment and to identify an alternate dosing strategy. In study 1, data from adult patients receiving linezolid for >= 10 days were retrospectively reviewed to determine the frequency of thrombocytopenia in patients with and without renal impairment. Time-to-event analyses were performed using Cox proportional-hazards models. In study 2, population pharmacokinetic modeling was employed to build covariate-structured models using an independent data set of linezolid concentrations obtained during routine therapeutic drug monitoring (TDM). Monte Carlo simulations were performed to identify linezolid dosing regimens that maximized attainment of therapeutic trough concentrations (2 to 8 mg/liter) across various renal-function groups. Toxicity analysis (study 1) included 341 patients, 133 (39.0%) with renal impairment. Thrombocytopenia occurred more frequently among patients with renal impairment (42.9% versus 16.8%; P < 0.001), and renal impairment was independently associated with this toxicity in multivariable analysis (adjusted hazard ratio [aHR], 2.37; 95% confidence interval [Cl], 1.52 to 3.68). Pharmacokinetic analyses (study 2) included 1,309 linezolid concentrations from 603 adult patients. Age, body surface area, and estimated glomerular filtration rate (eGFR) were identified as covariates of linezolid clearance. Linezolid dose reductions improved the probability of achieving optimal exposures in simulated patients with eGFR values of <60 ml/min. Thrombocytopenia occurs more frequently in patients with renal impairment receiving standard linezolid doses. Linezolid dose reduction and trough-based TDM are predicted to mitigate this treatment-limiting toxicity.
机译：尽管有证据表明肾脏损伤增加了患者，但对于所有患者施用LINEZOLID作为固定剂量给予固定剂量。这些研究的目标是评估血小板减少血小阴症的风险，肾脏损伤中具有标准剂量线唑，并鉴定替代给药策略。在研究1中，回顾性地审查了接受LINZOLID的成年患者的数据，以确定患有肾损伤患者血小板减少症的血小板减少症的频率。使用Cox比例危险模型进行时间 - 事件分析。在研究2中，使用人口药代动力学建模，使用在常规治疗药物监测（TDM）期间获得的独立数据集进行了独立数据集的共毒浓度。进行蒙特卡罗模拟以确定线唑醛给药方案，可在各种肾功能群中最大化治疗槽浓度（2至8毫克/升）。毒性分析（研究1）包括341名患者，133名（39.0％），肾脏损伤。肾脏损伤患者血小板减少症更频繁地发生（对比16.8％; P <0.001），肾损伤与多变量分析中的这种毒性有独立相关（调整后危险比[AHR]，2.37; 95％置信区间[CL] ，1.52至3.68）。药代动力学分析（研究2）包括来自603例成年患者的1,309次线唑胺浓度。年龄，体表面积和估计的肾小球过滤速率（EGFR）被鉴定为LINIZOLID间隙的协变量。 LINEzolid剂量减少改善了在模拟患者中实现了<60mL / min的模拟患者的最佳暴露的可能性。血小板减少症在接受标准LINZOLID剂量的肾损伤患者中更频繁地发生。预测线毒剂量减少和基于槽的TDM以减轻这种限制的毒性。

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