From the Department of Pediatrics, Division of Critical Care Medicine, CHU Sainte-Justine, Montreal, QC, Canada.
Department of Anesthesiology and Critical Care Medicine.
Pediatr Infect Dis J. 2022 Mar 1;41(3):217-223. doi: 10.1097/INF.0000000000003371.
Cefepime is a first-line therapy for Gram-negative infections in children on extracorporeal membrane oxygenation. Cefepime pharmacokinetics (PK) in children on extracorporeal membrane oxygenation still needs to be better established.
This was a prospective single-center PK study. A maximum of 12 PK samples per patient were collected in children <18 years old on extracorporeal membrane oxygenation who received clinically indicated cefepime. External validation of a previously published population PK model was performed by applying the model in a new data set. The predictive performance of the model was determined by calculating prediction errors. Because of poor predictive performance, a revised model was developed using NONMEM and a combined data set that included data from both studies. Dose-exposure simulations were performed using the final model. Optimal dosing was judged based on the ability to maintain free cefepime concentrations above the minimal inhibitory concentration (MIC) for 68% and 100% of the dosing interval.
Seventeen children contributed 105 PK samples. The mean (95% CI) and median (interquartile range) prediction errors were 33.7% (19.8-47.7) and 17.5% (-22.6 to 74.4). A combined data set was created, which included 33 children contributing 310 PK samples. The final improved 2-compartment model included weight and serum creatinine on clearance and oxygenator day and blood transfusion on volume of the central compartment. At an MIC of 8 mg/L, 50 mg/kg/dose every 8 hours reached target concentrations.
Dosing intervals of 8 hours were needed to reach adequate concentrations at an MIC of 8 mg/L. Longer dosing intervals were adequate with higher serum creatinine and lower MICs.
头孢吡肟是体外膜肺氧合患儿革兰氏阴性感染的一线治疗药物。但头孢吡肟在体外膜肺氧合患儿中的药代动力学（PK）仍需进一步明确。
这是一项前瞻性单中心 PK 研究。在接受临床指示的头孢吡肟治疗的体外膜肺氧合患儿中，每例患者最多采集 12 个 PK 样本。通过将模型应用于新数据集，对先前发表的群体 PK 模型进行外部验证。通过计算预测误差来确定模型的预测性能。由于预测性能不佳，使用 NONMEM 和包含两项研究数据的合并数据集开发了修订后的模型。使用最终模型进行剂量-暴露模拟。根据维持游离头孢吡肟浓度超过最低抑菌浓度（MIC）的 68%和 100%给药间隔的能力来判断最佳给药方案。
17 名儿童贡献了 105 个 PK 样本。平均（95%CI）和中位数（四分位距）预测误差分别为 33.7%（19.8-47.7）和 17.5%（-22.6-74.4）。创建了一个合并数据集，其中包括 33 名儿童贡献的 310 个 PK 样本。最终改进的 2 室模型包括清除率和氧合器日的体重和血清肌酐以及中央隔室的输血体积。在 MIC 为 8mg/L 时，50mg/kg/剂量每 8 小时给药可达到目标浓度。
在 MIC 为 8mg/L 时，需要 8 小时的给药间隔才能达到足够的浓度。随着血清肌酐升高和 MIC 降低，较长的给药间隔也是足够的。
