Vossen M G, Knafl D, Haidinger M, Lemmerer R, Unger M, Pferschy S, Lamm W, Maier-Salamon A, Jäger W, Thalhammer F
Clinical Division of Infectious Disease, Department of Medicine I, Medical University of Vienna, Vienna, Austria
Clinical Division of Infectious Disease, Department of Medicine I, Medical University of Vienna, Vienna, Austria.
Antimicrob Agents Chemother. 2017 Jul 25;61(8). doi: 10.1128/AAC.02425-16. Print 2017 Aug.
Critically ill patients often experience acute kidney injury and the need for renal replacement therapy in the course of their treatment in an intensive care unit (ICU). These patients are at an increased risk for candidiasis. Although there have been several reports of micafungin disposition during renal replacement therapy, to this date there are no data describing the elimination of micafungin during high-dose continuous venovenous hemodiafiltration with modified AN69 membranes. The aim of this prospective open-label pharmacokinetic study was to assess whether micafungin plasma levels are affected by continuous hemodiafiltration in critical ill patients using the commonly employed AN69 membrane. A total of 10 critically ill patients with micafungin treatment due to suspected or proven candidemia were included in this trial. Prefilter/postfilter micafungin clearance was measured to be 46.0 ml/min (±21.7 ml/min; = 75 individual time points), while hemofilter clearance calculated by the sieving coefficient was 0.0038 ml/min (±0.002 ml/min; = 75 individual time points). Total body clearance was measured to be 14.0 ml/min (±7.0 ml/min; = 12). The population area under the curve from 0 to 24 h (AUC) was calculated as 158.5 mg · h/liter (±79.5 mg · h/liter; = 13). In spite of high protein binding, no dose modification is necessary in patients receiving continuous venovenous hemodiafiltration with AN69 membranes. A dose elevation may, however, be justified in certain cases. (This study has been registered at ClinicalTrials.gov under identifier NCT02651038.).
重症患者在重症监护病房(ICU)接受治疗期间常发生急性肾损伤并需要进行肾脏替代治疗。这些患者发生念珠菌病的风险增加。尽管已有多篇关于肾脏替代治疗期间米卡芬净处置情况的报道,但迄今为止,尚无数据描述在使用改良AN69膜进行高剂量连续性静脉-静脉血液透析滤过期间米卡芬净的清除情况。这项前瞻性开放标签药代动力学研究的目的是评估在使用常用的AN69膜的重症患者中,连续性血液透析滤过是否会影响米卡芬净的血浆水平。本试验共纳入10例因疑似或确诊念珠菌血症而接受米卡芬净治疗的重症患者。预滤器/后滤器米卡芬净清除率测得为46.0 ml/分钟(±21.7 ml/分钟;n = 75个个体时间点),而通过筛分系数计算的血液滤过器清除率为0.0038 ml/分钟(±0.002 ml/分钟;n = 75个个体时间点)。全身清除率测得为14.0 ml/分钟(±7.0 ml/分钟;n = 12)。0至24小时的群体药时曲线下面积(AUC)计算为158.5 mg·小时/升(±79.5 mg·小时/升;n = 13)。尽管蛋白结合率高,但接受AN69膜连续性静脉-静脉血液透析滤过的患者无需调整剂量。然而,在某些情况下增加剂量可能是合理的。(本研究已在ClinicalTrials.gov注册,标识符为NCT02651038。)