Suk Pavel, Rychlíčková Jitka, Součková Lenka, Kubíčková Vendula, Šíma Martin, Šitina Michal, Urbánek Karel, Šrámek Vladimír
International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Anaesthesiology and Intensive Care, St. Anne's University Hospital Brno and Faculty of Medicine, Masaryk University Brno, Czech Republic.
International Clinical Research Center, St. Anne's University Hospital Brno, Brno, Czech Republic; Department of Anaesthesiology and Intensive Care, St. Anne's University Hospital Brno and Faculty of Medicine, Masaryk University Brno, Czech Republic; Department of Pharmacology, Faculty of Medicine, Masaryk University, Brno, Brno, Czech Republic.
Int J Antimicrob Agents. 2025 Nov;66(5):107582. doi: 10.1016/j.ijantimicag.2025.107582. Epub 2025 Jul 29.
Colistin is recognized as the last-resort antibiotic for treating infections caused by multidrug-resistant Gram-negative bacteria, especially in critically ill patients. However, its interference with the extracorporeal membrane oxygenation (ECMO) circuit may affect the achievement of therapeutic targets. The COL-ECMO2022 study aimed to verify the interference of colistin and its prodrug colistimethanesulphonate (CMS) with ECMO.
A prospective pharmacokinetic phase IV study included critically ill adults in whom the parenteral colistin was part of standard medical care. A maximum of three dosing intervals were monitored for each patient. CMS and colistin concentrations were measured by HPLC-MS. ECMO and non-ECMO patients were compared by average steady-state colistin concentration (C), population pharmacokinetic model (ECMO as a covariate), and linear mixed-effect model (LMEM).
Eighteen patients and 40 monitored dosing intervals were analyzed. Median C was non-significantly lower in 7 patients on ECMO (4.3 [3.5-6.3] mg/L) than in 11 non-ECMO patients (5.2 [4.2-11.5] mg/L) (by 18%; P = 0.551). ECMO was not a significant covariate for any pharmacokinetic parameter in the population PK model. Although LMEM proved significant adsorption of CMS on the ECMO circuit, colistin concentrations were not significantly influenced.
No significant differences in colistin plasma concentrations were detected; therefore, CMS dosage adjustment is unnecessary in patients on ECMO.
黏菌素被认为是治疗多重耐药革兰氏阴性菌感染的最后一道抗生素防线，尤其是在重症患者中。然而，它对体外膜肺氧合（ECMO）回路的干扰可能会影响治疗目标的实现。COL-ECMO2022研究旨在验证黏菌素及其前药黏菌素甲磺酸钠（CMS）对ECMO的干扰。
一项前瞻性药代动力学IV期研究纳入了接受肠外黏菌素作为标准医疗护理一部分的成年重症患者。每位患者最多监测三个给药间隔。通过高效液相色谱-质谱法测量CMS和黏菌素浓度。通过平均稳态黏菌素浓度（C）、群体药代动力学模型（将ECMO作为协变量）和线性混合效应模型（LMEM）对ECMO患者和非ECMO患者进行比较。
分析了18例患者和40个监测的给药间隔。7例接受ECMO治疗的患者的中位C（4.3 [3.5 - 6.3] mg/L）略低于11例非ECMO患者（5.2 [4.2 - 11.5] mg/L），但差异无统计学意义（降低了18%；P = 0.551）。在群体药代动力学模型中，ECMO不是任何药代动力学参数的显著协变量。虽然LMEM证明CMS在ECMO回路上有显著吸附，但黏菌素浓度未受到显著影响。
未检测到黏菌素血浆浓度有显著差异；因此，接受ECMO治疗的患者无需调整CMS剂量。
