König Christina, Braune Stephan, Roberts Jason A, Nierhaus Axel, Steinmetz Oliver M, Baehr Michael, Frey Otto R, Langebrake Claudia, Kluge Stefan
Hospital Pharmacy, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
Department of Intensive Care Medicine, University Medical Centre Hamburg-Eppendorf, Hamburg, Germany.
J Antimicrob Chemother. 2017 May 1;72(5):1433-1440. doi: 10.1093/jac/dkw592.
To describe the population PKs of ceftazidime in critically ill patients receiving sustained low-efficiency dialysis (SLED).
This study was performed in ICUs of a university hospital. We collected blood samples during three consecutive days of SLED sessions in patients receiving ceftazidime. Concentration versus time curves were analysed using a population PKs approach with Pmetrics ® . Monte Carlo simulation for the first 24 h including a 6 h SLED session was performed with the final model. The fractional target attainment against the MIC of Pseudomonas aeruginosa was executed using targets of 50 and 100% fT > MIC .
In total, 211 blood samples of 16 critically ill patients under SLED were collected. SLED treatments were 299.3 (68.4) min in duration. A two-compartment linear population PK model was most appropriate. The mean (SD) CL of ceftazidime on SLED, and off SLED were 5.32 (3.2), 1.06 (1.0) L/h respectively. The PTA for 50% fT > MIC for a dose of 1 g intravenously every 8 h was 98%. Assuming a target of 100% fT > MIC a dose of 2 g every 12 h covers isolates with MIC ≤8 mg/L with a PTA of 96%.
In critically ill patients receiving SLED, ceftazidime 1 g every 8 h and ceftazidime 2 g every 12 h appear to be sufficient for achieving traditional (50% fT > MIC ) and aggressive PD targets (100% fT > MIC ) for susceptible isolates (MIC ≤8 mg/L), respectively.
描述接受持续性低效透析（SLED）的重症患者中头孢他啶的群体药代动力学。
本研究在一家大学医院的重症监护病房进行。我们在接受头孢他啶治疗的患者进行SLED治疗的连续三天内采集血样。使用Pmetrics®软件采用群体药代动力学方法分析浓度-时间曲线。利用最终模型对包括6小时SLED治疗期在内的最初24小时进行蒙特卡洛模拟。针对铜绿假单胞菌的最低抑菌浓度（MIC），采用50%和100%的游离药物浓度高于最低抑菌浓度（fT＞MIC）的目标来执行目标达成率分析。
总共收集了16例接受SLED治疗的重症患者的211份血样。SLED治疗的持续时间为299.3（68.4）分钟。两室线性群体药代动力学模型最为合适。SLED治疗期间和非SLED治疗期间头孢他啶的平均清除率（SD）分别为5.32（3.2）、1.06（1.0）L/小时。每8小时静脉注射1g剂量时，50% fT＞MIC的目标达成率为98%。假设目标为100% fT＞MIC，每12小时2g的剂量可覆盖MIC≤8mg/L的菌株，目标达成率为96%。
在接受SLED治疗的重症患者中，每8小时1g头孢他啶和每12小时2g头孢他啶似乎分别足以实现针对敏感菌株（MIC≤8mg/L）的传统目标（50% fT＞MIC）和积极的药代动力学/药效学目标（100% fT＞MIC）。
