Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Germany; Hospital Pharmacy, University Medical Center Hamburg-Eppendorf, Germany.
Department of Intensive Care Medicine, University Medical Center Hamburg-Eppendorf, Germany.
Clin Microbiol Infect. 2022 Jul;28(7):1022.e9-1022.e16. doi: 10.1016/j.cmi.2022.02.017. Epub 2022 Feb 17.
In difficult-to-treat infections such as nosocomial ventriculitis, meropenem exposure in the infected compartment is often uncertain but crucial for antibacterial effects. The aim of this study was to investigate the cerebrospinal fluid (CSF) penetration of meropenem in patients with nosocomial ventriculitis and to derive a nomograph to predict effective meropenem doses as a function of clinical parameters.
Retrospective patient data including meropenem serum and CSF levels as well as CSF inflammation markers were analyzed using NONMEM to assess the general pharmacokinetics and CSF penetration. Monte Carlo simulations were used to evaluate different meropenem dosing regimens. Probability of target attainment (PTA) in CSF was assessed, and a nomograph to achieve a target twice the minimal inhibitory concentration (MIC) during the dosing interval (100 %fT ) was developed.
A one-compartment model with meropenem clearance dependent on the estimated glomerular filtration rate (CKD-EPI eGFR, p < 0.001) best described meropenem serum pharmacokinetics of 51 critically ill patients. CSF penetration ratio was correlated with the amount of protein in CSF (p < 0.001), with higher CSF protein levels accounting for higher penetration ratios. Preserved renal function (CKD-EPI eGFR >50 mL/min/1.73 m) and low CSF protein levels (<500 mg/L) resulted in 80% PTA 100 %fT ) for a meropenem dose of 6 g/24 h.
High interindividual variability in meropenem CSF concentration was observed in patients with nosocomial ventriculitis. A nomograph to predict the daily meropenem dose required for target attainment for a given eGFR and CSF protein count was developed.
在治疗困难的感染，如医院获得性脑室炎，在感染部位的美罗培南暴露往往是不确定的，但对抗菌效果至关重要。本研究旨在探讨医院获得性脑室炎患者美罗培南的脑脊液（CSF）渗透，并得出一个列线图来预测有效美罗培南剂量作为临床参数的函数。
使用 NONMEM 分析包括美罗培南血清和 CSF 水平以及 CSF 炎症标志物的回顾性患者数据，以评估一般药代动力学和 CSF 渗透。蒙特卡罗模拟用于评估不同的美罗培南给药方案。评估 CSF 中的目标达标概率（PTA），并开发一个列线图，以在给药间隔（100%fT）期间达到目标两次最小抑菌浓度（MIC）。
一个与估计肾小球滤过率（CKD-EPI eGFR，p < 0.001）相关的单室模型可最好地描述 51 例危重病患者的美罗培南血清药代动力学。CSF 穿透率与 CSF 中蛋白质的量相关（p < 0.001），较高的 CSF 蛋白水平解释了较高的穿透率。保留的肾功能（CKD-EPI eGFR > 50 mL/min/1.73 m）和低 CSF 蛋白水平（<500 mg/L）导致美罗培南剂量为 6 g/24 h 时 80% PTA（100%fT）。
在患有医院获得性脑室炎的患者中观察到美罗培南 CSF 浓度的个体间高度变异性。开发了一个列线图，用于预测在给定 eGFR 和 CSF 蛋白计数下达到目标所需的美罗培南每日剂量。
