中国药物警戒 ›› 2025, Vol. 22 ›› Issue (8): 889-895.
DOI: 10.19803/j.1672-8629.20240822

• 基础与临床研究 • 上一篇    下一篇

脓毒症伴急性肾损伤重症患者利奈唑胺剂量分析

孙雅1, 王旭2, 孙志1, 周玉冰1*   

  1. 1郑州大学第一附属医院药学部,河南省精准临床药学应用与转化工程研究中心,河南 郑州 450052;
    2郑州大学第一附属医院病案管理科,河南 郑州 450052
  • 收稿日期:2024-10-23 出版日期:2025-08-15 发布日期:2025-08-13
  • 通讯作者: *周玉冰,男,博士,副主任药师,副教授·硕导,肿瘤药理学与临床药学。E-mail: zhouyubing1982@163.com
  • 作者简介:孙雅,女,硕士,副主任药师,临床药学。
  • 基金资助:
    国家自然科学基金资助项目（82374018）

Dose Analysis of Linezolid in Severe Patients with Sepsis Complicated with Acute Kidney Injury

SUN Ya1, WANG Xu2, SUN Zhi1, ZHOU Yubing1*   

  1. 1Department of Pharmacy, Henan Province Engineering Research Center of Application & Translation of Precision Clinical Pharmacy, the First Affiliated Hospital of Zhengzhou University, Zhengzhou Henan 450052, China;
    2Department of Medical Records Management, the First Affiliated Hospital of Zhengzhou University, Zhengzhou Henan 450052, China
  • Received:2024-10-23 Online:2025-08-15 Published:2025-08-13

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摘要： 目的 分析利奈唑胺在脓毒症伴急性肾损伤重症患者中的剂量,优化脓毒症伴急性肾损伤重症患者群体中的利奈唑胺治疗方案,为其临床用药提供参考。方法 选取2022年5月1日至2023年8月31日本院重症监护室（ICU）病房使用利奈唑胺治疗的23例脓毒症伴急性肾损伤患者,回顾性分析患者静脉给药后的血药浓度检测结果,计算利奈唑胺的药动学参数。运用蒙特卡洛模拟,获得现给药方案[600 mg,每12h给药1次（q12h）]治疗不同革兰阳性（G+）球菌[金黄色葡萄球菌、肺炎链球菌、表皮葡萄球菌、耐甲氧西林金黄色葡萄球菌（MRSA）、粪肠球菌、屎肠球菌]感染时的达标概率（PTA）、累积反应分数（CFR）,评估给药方案（600 mg,q12h）在细菌清除方面的疗效。结果 对于脓毒症伴急性肾损伤患者,利奈唑胺采用600 mg,q12h给药方案,当最低抑菌浓度（MIC）≤2 mg·L-1时,其对金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌、屎肠球菌、肺炎链球菌可达到满意的抗菌效果（PTA=100%）,CFR分别为95.42%、92.03%、93.15%、91.45%、98.81%。但对MRSA的抗菌效果不理想（PTA<90%）,CFR为49.45%。利奈唑胺的稳态最小血药浓度（ ）水平与协变量用药后7 d血小板计数呈负相关。结论 对于利奈唑胺静脉治疗脓毒症伴急性肾损伤患者金黄色葡萄球菌、表皮葡萄球菌、粪肠球菌、屎肠球菌和肺炎链球菌感染时,当MIC≤2 mg·L-1时,600 mg,q12h给药方案能获得良好的抗菌效果,对此类患者可适量减少给药剂量或延长给药间隔时间。此外,利奈唑胺对MRSA的抗菌效果不理想时,此时可相应增加给药剂量。利奈唑胺600 mg,q12h给药7 d后血小板减少症的发生风险较高,在保证抗菌效果的同时可根据血药浓度检测结果适当调整给药剂量。

关键词: 利奈唑胺, 脓毒症, 蒙特卡洛模拟, 静脉给药, 革兰阳性球菌

Abstract: Objective To analyze the dosage of linezolid in severe patients with sepsis and acute kidney injury, optimize treatment plans, and to provide a reference for clinical medications. Methods Twenty-three patients with sepsis complicated with acute kidney injury who were treated with linezolid in the intensive care unit (ICU) of a hospital between May 1, 2022 and August 31, 2023 were selected. The test results of serum drug concentrations of these patients after intravenous administration were retrospectively analyzed while the pharmacokinetic parameters of linezolid were calculated. Monte Carlo simulation was used to calculate the probability target attainment (PTA) and cumulative fraction of response (CFR) of the current administration regimen (600 mg, q12h) against different gram-positive (G+) bacteria [Staphylococcus aureus, Streptococcus pneumoniae, Staphylococcus epidermidis, methicillin-resistant Staphylococcus aureus (MRSA), Enterococcus faecalis, Enterococcus faecium]. The efficacy of the administration regimen was evaluated in terms of bacterial clearance. Results Among patients with sepsis complicated with acute kidney injury, the administration regimen was linzolid (600 mg, q12h). At the minimum inhibitory concentration (MIC) of 2 mg·L-1 or less, this regimen could deliver satisfactory antibacterial effect (PTA=100%) against Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium and Streptococcus pneumoniae. The CFR was 95.42%, 92.03%, 93.15%, 91.45% and 98.81%, respectively. However, the antibacterial effect against MRSA was undesirable in that the PTA was less than 90%) and the CFR was no more than 49.45%. The steady-state minimum plasma concentration ( ) of linezolid was negatively correlated with platelet counts at 7 d after covariate medication. Conclusion During the intravenous treatment of Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Enterococcus faecium and Streptococcus pneumoniae in patients with sepsis and acute kidney injury, the regimen of 600 mg, q12h can produce good antibacterial effect when the MIC is less than 2 mg·L-1. The dose can be appropriately reduced or the interval extended for such patients. However, the antibacterial effect of linezolid against MRSA is not so good, so the dose can be increased accordingly. The risk of thrombocytopenia increases after 7 days of medication with linezolid 600 mg, q12h. The dosage can be adjusted according to the serum drug concentration to ensure the antibacterial effect.

Key words: Linezolid, Sepsis, Monte Carlo Simulation, Intravenous Administration, Gram-Positive Cocci

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