Xu Mi, Chen Na, Yu Yong-Wei, Pan Xiang-Ying, Li Tong
Department of Critical Care Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.
Department of Clinical Pharmaceutical, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People's Republic of China.
Infect Drug Resist. 2024 Dec 25;17:5815-5825. doi: 10.2147/IDR.S486169. eCollection 2024.
With the development of extracorporeal membrane oxygenation (ECMO) technology, the duration of ECMO support has gradually increased, leading to an increased risk of ECMO-related bacterial resistance. Polymyxin B (PMB) is used to treat drug-resistant bacterial infections. However, the pharmacokinetic (PK) parameters of antibiotics may change during ECMO, resulting in over- or under-exposure. This study aimed to clarify the changes in PK parameters and identify factors influencing PMB levels in patients receiving venovenous or venoarterial ECMO.
A prospective PK study was performed in 11 patients receiving ECMO with resistant bacteria. After reaching a steady state, the drug concentrations of PMB pre- and post-oxygenator were measured. Nonlinear mixed-effects modelling was used to construct a population PK model for PMB. Microbial results were assessed using repeated cultures at the end of treatment. Semiquantitative microbial culture results were used to form clearance and uncleared groups.
The PMB concentrations were not significantly different between pre- and post-oxygenator. A two-compartment model best described the PK of PMB. ECMO flow rate was included as a covariate of clearance (CL). Continuous renal replacement therapy (CRRT) were included as covariates on the volume of the central compartment. The PK parameters central compartment, volume of the peripheral compartment, CL, and inter-compartmental clearance or flow rate(Q) were 20.41 L, 9.86 L, 3.75 L/h, and 3.82 L/h. 7 patients (63.64%) had two consecutive negative bacterial cultures at discharge. The C shows a significant difference between clearance group (2.26±0.72) and uncleared group (1.25±0.24), P<0.05.
There were no significant differences in PMB concentrations between pre- and post-oxygenator. The PK of PMB may be altered in patients receiving CRRT-ECMO. The ECMO flow rate is strongly correlated with the CL. The C is correlated with the bacterial clearance rate. In clinical practice, increasing the incidence of therapeutic drug monitoring may improve the clinical outcomes.
随着体外膜肺氧合（ECMO）技术的发展，ECMO支持时间逐渐延长，导致ECMO相关细菌耐药风险增加。多黏菌素B（PMB）用于治疗耐药细菌感染。然而，抗生素的药代动力学（PK）参数在ECMO期间可能会发生变化，导致暴露过量或不足。本研究旨在阐明PK参数的变化，并确定影响接受静脉-静脉或静脉-动脉ECMO患者PMB水平的因素。
对11例接受ECMO治疗且伴有耐药菌感染的患者进行了一项前瞻性PK研究。达到稳态后，测量氧合器前后PMB的药物浓度。采用非线性混合效应模型构建PMB的群体PK模型。在治疗结束时通过重复培养评估微生物结果。使用半定量微生物培养结果形成清除组和未清除组。
氧合器前后PMB浓度无显著差异。二室模型最能描述PMB的PK。ECMO流速作为清除率（CL）的协变量纳入。连续性肾脏替代治疗（CRRT）作为中央室容积的协变量纳入。中央室、外周室容积、CL以及室间清除率或流速（Q）的PK参数分别为20.41 L、9.86 L、3.75 L/h和3.82 L/h。7例患者（63.64%）出院时连续两次细菌培养阴性。清除组（2.26±0.72）与未清除组（1.25±0.24）的C存在显著差异，P<0.05。
氧合器前后PMB浓度无显著差异。接受CRRT-ECMO的患者中PMB的PK可能会改变。ECMO流速与CL密切相关。C与细菌清除率相关。在临床实践中，增加治疗药物监测的频率可能会改善临床结局。
