接受连续性肾脏替代治疗的重症患者的大剂量黏菌素药代动力学
High-dose colistin pharmacokinetics in critically ill patients receiving continuous renal replacement therapy.
作者信息
De Pascale Gennaro, Lisi Lucia, Cutuli Salvatore Lucio, Marinozzi Carlotta, Palladini Altea, Ferrando Elena Sancho, Tanzarella Eloisa Sofia, Lombardi Gianmarco, Grieco Domenico Luca, Caroli Alessandro, Xhemalaj Rikardo, Cascarano Laura, Ciotti Gabriella Maria Pia, Sandroni Claudio, Sanguinetti Maurizio, Navarra Pierluigi, Antonelli Massimo
机构信息
Dipartimento di Scienze Biotecnologiche di Base, Cliniche Intensivologiche e Perioperatorie, Università Cattolica del Sacro Cuore, Rome, Italy.
Dipartimento di Scienze dell'Emergenza, Anestesiologiche e della Rianimazione, Fondazione Policlinico Universitario A. Gemelli IRCCS, Cattolica del Sacro Cuore Largo A. Gemelli 8, Rome, 00168, Italy.
出版信息
Ann Intensive Care. 2024 Sep 28;14(1):152. doi: 10.1186/s13613-024-01384-1.
BACKGROUND
Colistin, administered as intravenous colistimethate (CMS), is still used in the critical care setting and current guidelines recommend high dosage CMS in patients undergoing continuous renal replacement therapy (CRRT). Due to the paucity of real-life data, we aimed to describe colistin pharmacokinetic/pharmacodynamic (PK/PD) profile in a cohort of critically ill patients with infections due to carbapenem-resistant (CR) bacteria undergoing CRRT.
RESULTS
All consecutive patients admitted to three Intensive Care Units (ICUs) of a large metropolitan University Hospital, treated with colistin for at least 48 h at the dosage of 6.75 MUI q12, after 9 MIU loading dose, and undergoing CRRT were included. After the seventh dose, patients underwent blood serial sampling during a time frame of 24 h. We included 20 patients, who had CR-Acinetobacter baumannii ventilator-associated pneumonia and were characterized by a median SAPS II and SOFA score of 41 [34.5-59.3] and 9 [6.7-11], respectively. Fifteen patients died during ICU stay and six recovered renal function. Median peak and trough colistin concentrations were 16.6 mcg/mL [14.8-20.6] and 3.9 mcg/mL [3.3-4.4], respectively. Median area under the time-concentration curve (AUC) and average steady-state concentration (C) were 193.9 mcg h/mL [170.6-208.6] and 8.07 mcg/mL [7.1-8.7]. Probability of target attainment of colistin pharmacodynamics according to the fAUC/MIC target ≥ 12 was 100% for MIC ≤ 2 mcg/mL and 85% for MIC = 4 mcg/ML, although exceeding the toxicity limit of C 3-4 mcg/mL.
CONCLUSIONS
In critically ill patients with CR infections undergoing CRRT, recommended CMS dosage resulted in colistin plasmatic levels above bacterial MIC, but exceeding the safety C. limit.
TRIAL REGISTRATION
This trial was registered in ClinicalTrials.gov on 23/07/2021 with the ID NCT04995133 (https//clinicaltrials.gov/study/NCT04995133).
背景
多黏菌素以静脉注射多黏菌素甲磺酸钠（CMS）的形式给药，仍用于重症监护环境，当前指南建议对接受持续肾脏替代治疗（CRRT）的患者使用高剂量CMS。由于缺乏实际数据，我们旨在描述一组因耐碳青霉烯类（CR）细菌感染而接受CRRT的重症患者的多黏菌素药代动力学/药效学（PK/PD）特征。
结果
纳入了一家大型都市大学医院三个重症监护病房（ICU）的所有连续入院患者，这些患者接受多黏菌素治疗至少48小时，剂量为每12小时6.75 MU，在给予9 MU负荷剂量后接受CRRT。在第七剂后，患者在24小时内进行了系列血样采集。我们纳入了20例患有CR鲍曼不动杆菌呼吸机相关性肺炎的患者，其急性生理与慢性健康状况评分系统II（SAPS II）和序贯器官衰竭评估（SOFA）评分中位数分别为41[34.5 - 59.3]和9[6.7 - 11]。15例患者在ICU住院期间死亡，6例恢复了肾功能。多黏菌素的峰浓度和谷浓度中位数分别为16.6 mcg/mL[14.8 - 20.6]和3.9 mcg/mL[3.3 - 4.4]。时间 - 浓度曲线下面积（AUC）和平均稳态浓度（C）中位数分别为193.9 mcg·h/mL[170.6 - 208.6]和8.07 mcg/mL[7.1 - 8.7]。根据fAUC/MIC目标≥12，多黏菌素药效学目标达成概率对于MIC≤2 mcg/mL为100%，对于MIC = 4 mcg/ML为85%，尽管超过了C 3 - 4 mcg/mL的毒性限值。
结论
在因CR感染而接受CRRT的重症患者中，推荐的CMS剂量导致多黏菌素血浆水平高于细菌MIC，但超过了安全的C限值。
试验注册
本试验于2021年7月23日在ClinicalTrials.gov注册，标识符为NCT04995133（https//clinicaltrials.gov/study/NCT04995133）。
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