Drug monitoring of antiinfectives in critically ill patients receiving extracorporeal life support - a prospective observational pilot study

接受体外生命支持的危重患者抗感染药物的药物监测——一项前瞻性观察性试点研究

• 批准号: 400675671
• 负责人: Dr. Elisabeth Adam
• 金额: --
• 依托单位: Klinik für Anästhesiologie, Intensivmedizin und Schmerztherapie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2019
• 资助国家: 德国
• 起止时间: 2018-12-31 至 2021-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/400675671?language=en
• 关键词: Drug; monitoring; antiinfectives; critically; ill

About 70% of critically ill patients require antiinfective therapy. Optimal antibiotic dosing is key to improve patient survival, reduce toxic effects and minimise the emergence of bacterial resistance. However, there is a growing body of evidence demonstrating the existence of significant changes in pharmacokinetics (PK) in intensive care patients, particularly those with extracorporeal therapy (extracorporeal membrane oxygenation (ECMO), continuous renal replacement therapy (CRRT)). Existing antiinfective dosing regimens assume a "normal" PK; currently there are no evidence-based antiinfective dosing guidelines for critically ill patients available. The current recommendations of the Paul-Ehrlich Society and the Surviving Sepsis Campaign therefore recommend explicitly appliance of a therapeutic drug monitoring (TDM) for intensive care patients to individually adjust dosing and to avoid potential over- or underdosing.To characterize the effects of extracorporal therapy for critically ill patients, we designed a prospective pilot observational study using a drug monitoring. Six antiinfectives (meropenem, teicoplanin, linezolid, piperacillin / tazobactam, levofloxacin and aciclovir) will be investigated as index substances for the various antiinfective groups. A total of 100 patients, divided into 5 groups of 20 patients, will be examined in this study: 1. venovenous (vv)-ECMO, 2. venoarterial (va)-ECMO, 3. vv-ECMO + CRRT, 4. va-ECMO + CRRT, 5. control group. Sampling for determination of trough and peak levels of the study substances will take place during the different dosing intervals. Patients will be included at the beginning of ECMO therapy within 24-48h after start of an antiinfective therapy with at least one of the index-substances; observation period will be a total of 5 days. The collected data will be analyzed to identify covariates associated with changes in PK for the 6 different antiinfectives in critically ill patients receiving extracorporeal therapy. Using the comprehensive data set collected, the pharmacokinetic profile of the 6 antiinfectives as well as other influencing factors will be constructed to assess the need for dose adjustment of antiinfective agents in these patients. This prospective observational trial addresses the current knowledge deficiency with the aim to derive relevant effects of extracorporeal therapy and clinical patient characteristics for the treatment with meropenem, teicoplanin, linezolid, piperacillin/tazobactam, levofloxacin and acyclovir. With these relevant results, adapted dosing of antiinfectives can probably be improved in critically ill patients with extracorporeal therapy in future.

约70%的重症患者需要抗感染治疗。最佳抗生素剂量是提高患者生存率、减少毒性作用和最大限度减少细菌耐药性出现的关键。然而，越来越多的证据表明重症监护患者的药代动力学（PK）存在显著变化，特别是接受体外治疗（体外膜肺氧合（ECMO）、连续性肾脏替代治疗（CRRT））的患者。现有的抗感染给药方案假定PK“正常”;目前尚无针对危重患者的循证抗感染给药指南。目前的建议，保罗-埃利希协会和生存败血症运动，因此建议明确的治疗药物监测（TDM）的重症监护患者单独调整给药，以避免潜在的过度或欠dosed.To表征的影响，重症患者的肠外治疗，我们设计了一个前瞻性的试点观察性研究，使用药物监测。将研究6种抗感染药（美罗培南、替考拉宁、利奈唑胺、哌拉西林/他唑巴坦、左氧氟沙星和阿昔洛韦）作为各种抗感染药组的指示物质。共100例患者，分为5组，每组20例，将在本研究中进行检查：1。静脉-静脉（vv）-ECMO，2.静脉动脉（va）-ECMO，3. vv-ECMO + CRRT，4. va-ECMO + CRRT，5.对照组将在不同给药间隔期间进行采样，以测定研究物质的谷浓度和峰浓度。患者将在开始ECMO治疗时入组，在开始使用至少一种指标物质进行抗感染治疗后24- 48小时内入组;观察期共计5天。将对收集的数据进行分析，以确定与接受体外治疗的重症患者中6种不同抗感染药PK变化相关的协变量。使用收集的综合数据集，构建6种抗感染药的药代动力学特征以及其他影响因素，以评估这些患者是否需要调整抗感染药的剂量。这项前瞻性观察性试验解决了目前的知识缺陷，旨在获得美罗培南、替考拉宁、利奈唑胺、哌拉西林/他唑巴坦、左氧氟沙星和阿昔洛韦治疗的体外治疗的相关效应和临床患者特征。根据这些相关结果，未来可能会改善危重患者体外治疗中抗感染药物的适应性剂量。