Department of Pharmacy, National Center for Child Health and Development, Tokyo, Japan
Division of Infectious Diseases, Department of Medical Subspecialties, National Center for Child Health and Development, Tokyo, Japan.
Antimicrob Agents Chemother. 2021 Jan 20;65(2). doi: 10.1128/AAC.01909-20.
This study investigates the optimal meropenem (MEM) dosing regimen for critically ill pediatric patients, for which there is a lack of pharmacokinetic (PK) studies. We conducted a retrospective single-center PK and pharmacodynamic (PD) analysis of 34 pediatric intensive care unit patients who received MEM. Individual PK parameters were determined by a two-compartment analysis. The median (range) age and body weight were 1.4 (0.03 to 14.6) years and 8.9 (2.7 to 40.9) kg, respectively, and eight (23.5%) patients received continuous renal replacement therapy (CRRT), three of whom received extracorporeal membrane oxygenation. Renal function, the systemic inflammatory response syndrome (SIRS) score for the clearance (CL), and the use of CRRT for the central volume of distribution () were identified as significant covariates. The mean CL, , and peripheral volume of distribution () were 0.45 liters/kg/h, 0.49 liters/kg, and 0.34 liters/kg, respectively. The mean population CL of MEM increased by 35% in patients with SIRS and increased by 66% in patients on CRRT in the final model. Dosing simulations suggested that the standard dosing regimen provided insufficient PD exposures of a 100% free time above the MIC, and higher doses (40 to 80 mg/kg of body weight/dose every 8 h) with a prolonged 3-h infusion were required to ensure the appropriate PD exposures for patients with SIRS. Our PK model indicated that critically ill pediatric patients are at risk of subtherapeutic exposure under the standard dosing regimen of MEM. A larger, prospective investigation confirming the safety and efficacy of higher concentrations and prolonged infusion of MEM is necessary.
这项研究旨在探讨美罗培南（MEM）在危重症儿科患者中的最佳剂量方案，因为目前针对该人群的药代动力学（PK）研究还比较缺乏。我们对 34 例在儿科重症监护病房（PICU）接受 MEM 治疗的患者进行了回顾性单中心 PK 和药效动力学（PD）分析。采用两室模型分析确定个体 PK 参数。患者的中位（范围）年龄和体重分别为 1.4（0.03 至 14.6）岁和 8.9（2.7 至 40.9）kg，其中 8 例（23.5%）患者接受连续性肾脏替代治疗（CRRT），其中 3 例患者接受体外膜氧合治疗。肾功能、清除率的全身炎症反应综合征（SIRS）评分（CL）和 CRRT 对中央分布容积（）的影响被确定为重要的协变量。MEM 的平均 CL、和外周分布容积（）分别为 0.45 升/千克/小时、0.49 升/千克和 0.34 升/千克。在最终模型中，SIRS 患者的 MEM 群体 CL 增加了 35%，CRRT 患者的 CL 增加了 66%。给药模拟表明，标准剂量方案提供的 PD 暴露（游离时间超过 MIC 的 100%）不足，需要更高的剂量（40 至 80mg/kg/体重/剂量，每 8 小时一次）和延长 3 小时输注时间，以确保 SIRS 患者获得适当的 PD 暴露。我们的 PK 模型表明，MEM 标准剂量方案下，危重症儿科患者存在治疗不足的风险。需要进行更大规模的前瞻性研究，以确认更高浓度和延长 MEM 输注时间的安全性和有效性。
