Department of Pharmacology, Faculty of Medicine and Dentistry, Palacký University in Olomouc, Hněvotínská 3, Olomouc 775 15, Czech Republic.
Department of Anaesthesiology and Intensive Care, First Faculty of Medicine, Charles University in Prague, General University Hospital in Prague, U Nemocnice 2, Prague 2 128 08, Czech Republic.
Int J Antimicrob Agents. 2017 Mar;49(3):348-354. doi: 10.1016/j.ijantimicag.2016.12.005. Epub 2017 Feb 9.
Monte Carlo simulations allow prediction and comparison of concentration-time profiles arising from different dosing regimens in a defined population, provided a population pharmacokinetic model has been established. The aims of this study were to evaluate the population pharmacokinetics of imipenem in critically ill patients with hospital-acquired pneumonia (HAP) and to assess the probability of target attainment (PTA) and cumulative fraction of response (CFR) using EUCAST data. A two-compartment model based on a data set of 19 subjects was employed. Various dosage regimens at 0.5-h and 3-h infusion rates and as continuous infusion were evaluated against the pharmacodynamic targets of 20%fT, 40%fT and 100%fT. For the target of 40%fT, all 0.5-h infusion regimens achieved optimal exposures (CFR ≥ 90%) against Escherichia coli and Staphylococcus aureus, with nearly optimal exposure against Klebsiella pneumoniae (CFR ≥ 89.4%). The 3-h infusions and continuous infusion exceeded 97% CFR against all pathogens with the exception of Pseudomonas aeruginosa and Acinetobacter spp., where the maximum CFRs were 85.5% and 88.4%, respectively. For the 100%fT target, only continuous infusion was associated with nearly optimal exposures. Higher PTAs for the targets of 40%fT and 100%fT were achieved with 3-h infusions and continuous infusion in comparison with 0.5-h infusions; however, continuous infusion carries a risk of not reaching the MIC of less susceptible pathogens in a higher proportion of patients. In critically ill patients with HAP with risk factors for Gram-negative non-fermenting bacteria, maximum doses administered as extended infusions may be necessary.
蒙特卡罗模拟允许在已建立群体药代动力学模型的情况下，预测和比较不同给药方案在特定人群中产生的浓度-时间曲线。本研究旨在评估重症医院获得性肺炎（HAP）患者中亚胺培南的群体药代动力学，并使用 EUCAST 数据评估目标浓度达标概率（PTA）和累积反应分数（CFR）。采用基于 19 例患者数据集的两室模型。评估了 0.5 小时和 3 小时输注率以及连续输注的各种剂量方案，以达到药效学目标 20%fT、40%fT 和 100%fT。对于 40%fT 的目标，所有 0.5 小时输注方案均实现了针对大肠埃希菌和金黄色葡萄球菌的最佳暴露（CFR≥90%），对肺炎克雷伯菌的暴露接近最佳（CFR≥89.4%）。除铜绿假单胞菌和不动杆菌属外，所有 3 小时输注和连续输注均超过 97%的 CFR，其中最大 CFR 分别为 85.5%和 88.4%。对于 100%fT 的目标，只有连续输注与接近最佳的暴露相关。与 0.5 小时输注相比，3 小时输注和连续输注实现了针对 40%fT 和 100%fT 的目标的更高 PTA；然而，连续输注会增加患者中不能达到较不敏感病原体 MIC 的风险。在具有革兰氏阴性非发酵菌危险因素的重症 HAP 患者中，可能需要给予最大剂量作为延长输注。
