Population Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation: an ASAP ECMO Study
Population Pharmacokinetics of Piperacillin and Tazobactam in Critically Ill Patients Receiving Extracorporeal Membrane Oxygenation: an ASAP ECMO Study
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DOI：
10.1128/aac.01438-21
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发表时间：
2021-10-01
影响因子：
4.9
通讯作者：
Roberts, Jason A.
中科院分区：
文献类型：
--
作者：
Cheng, Vesa;Abdul-Aziz, Mohd H.;Roberts, Jason A.
我们的研究旨在描述体外膜氧合(ECMO)患者接受和不接受肾脏替代治疗(RRT)时哌拉西林和他唑巴坦的群体药代动力学(PK)。我们还旨在使用剂量模拟来确定这些患者组的最佳剂量策略。连续测定哌拉西林和他唑巴坦的血药浓度，数据采用总体PK方法进行分析，其中包括对患者和治疗协变量的分期测试。通过给药模拟确定了最优给药策略，使哌拉西林靶向暴露50%和100%的时间段自由药物浓度高于MIC(%FT(>；MIC))，毒性暴露大于360 mg/L。他唑巴坦目标的时间自由浓度的百分比>；2毫克/升也被评估。27名患者入选，其中14名患者同时接受RRT。哌拉西林和他唑巴坦均符合二室模型，体重指数、内生肌酐清除量和RRT是预测PK的重要指标。来自非ECMO患者的观察到的PK参数与公布的参数之间没有实质性差异。根据剂量模拟，在4小时内每6小时给药4.5克的方案在哌拉西林最低抑菌浓度为16毫克/升的情况下实现了很高的有效概率，同时患者暴露在3%的中毒浓度下。在接受ECMO和RRT的患者中，频率减少到每12小时给药一次，可降低中毒浓度的可能性，尽管这一比例保持在7%至9%。在ECMO患者中，哌拉西林和他唑巴坦的剂量应与危重患者的标准建议一致。
Our study aimed to describe the population pharmacokinetics (PK) of piperacillin and tazobactam in patients on extracorporeal membrane oxygenation (ECMO), with and without renal replacement therapy (RRT). We also aimed to use dosing simulations to identify the optimal dosing strategy for these patient groups. Serial piperacillin and tazobactam plasma concentrations were measured with data analyzed using a population PK approach that included staged testing of patient and treatment covariates. Dosing simulations were conducted to identify the optimal dosing strategy that achieved piperacillin target exposures of 50% and 100% fraction of time free drug concentration is above MIC (%fT(> MIC)) and toxic exposures of greater than 360 mg/liter. The tazobactam target of percentage of time free concentrations of > 2 mg/liter was also assessed. Twenty-seven patients were enrolled, of which 14 patients were receiving concurrent RRT. Piperacillin and tazobactam were both adequately described by two-compartment models, with body mass index, creatinine clearance, and RRT as significant predictors of PK. There were no substantial differences between observed PK parameters and published parameters from non-ECMO patients. Based on dosing simulations, a 4.5-g every 6 hours regimen administered over 4 hours achieves high probabilities of efficacy at a piperacillin MIC of 16 mg/liter while exposing patients to a < 3% probability of toxic concentrations. In patients receiving ECMO and RRT, a frequency reduction to every 12 hours dosing lowers the probability of toxic concentrations, although this remains at 7 to 9%. In ECMO patients, piperacillin and tazobactam should be dosed in line with standard recommendations for the critically ill.