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Population pharmacokinetics of vancomycin in paediatric patients with febrile neutropenia and augmented renal clearance: development of new dosing recommendations
Journal of Antimicrobial Chemotherapy ( IF 5.2 ) Pub Date : 2021-08-02 , DOI: 10.1093/jac/dkab302
Yuko Shimamoto 1 , Ruud H J Verstegen 1, 2 , Tomoyuki Mizuno 3, 4 , Tal Schechter 2, 5 , Upton Allen 2, 6 , Shinya Ito 1, 2
Affiliation  

Objectives The purpose of this study was to evaluate the influence of augmented renal clearance (ARC) on vancomycin clearance and provide dosage recommendations for paediatric patients with febrile neutropenia following HSCT. Methods A population pharmacokinetic analysis was performed based on a two-compartment model structure using a non-linear mixed-effect modelling approach. Monte Carlo simulations were conducted as a target attainment analysis of AUC between 400 mg·h/L and 650 mg·h/L for MRSA at an MIC of 1 mg/L. Results A total of 165 paediatric patients and 276 vancomycin serum concentrations were analysed in this study. Age, body weight, estimated glomerular filtration rate (eGFR) and fever (≥38.0°C) were identified as factors that significantly influenced vancomycin clearance. The median eGFR of the population was 143 mL/min/1.73 m2 and 34% of patients showed an eGFR ≥160 mL/min/1.73 m2, which may be classified as ARC. Our simulations showed that current dosing recommendations result in poor target attainment. In particular, children aged 6 months old to 6 years old with ARC require an initial vancomycin dose up to 35%–65% higher than the current dosing guidelines. Conclusions ARC is frequently observed in paediatric patients with post-HSCT febrile neutropenia, resulting in a significant increase in vancomycin clearance. We propose a vancomycin dosing strategy for children with febrile neutropenia following HSCT based on eGFR, age, weight and body temperature.

中文翻译:

万古霉素在发热性中性粒细胞减少症和肾清除率增加的儿科患者中的群体药代动力学:制定新的给药建议

目的 本研究的目的是评估增强肾清除率 (ARC) 对万古霉素清除率的影响,并为 HSCT 后发热性中性粒细胞减少症的儿科患者提供剂量建议。方法 基于二室模型结构,使用非线性混合效应建模方法进行群体药代动力学分析。进行蒙特卡罗模拟作为 MRSA 在 1 mg/L 的 MIC 下的 AUC 在 400 mg·h/L 和 650 mg·h/L 之间的目标达到分析。结果本研究共分析了165名儿科患者和276种万古霉素的血清浓度。年龄、体重、估计肾小球滤过率 (eGFR) 和发热 (≥38.0°C) 被确定为显着影响万古霉素清除率的因素。人群的中位 eGFR 为 143 mL/min/1。73 m2 和 34% 的患者显示 eGFR ≥160 mL/min/1.73 m2,可归类为 ARC。我们的模拟表明,当前的剂量建议导致目标实现不佳。特别是 6 个月至 6 岁患有 ARC 的儿童,万古霉素的初始剂量需要比目前的剂量指南高出 35%–65%。结论 ARC 常见于 HSCT 后发热性中性粒细胞减少的儿科患者,导致万古霉素清除率显着增加。我们根据 eGFR、年龄、体重和体温为 HSCT 后发热性中性粒细胞减少症儿童提出了万古霉素给药策略。患有 ARC 的 6 个月至 6 岁儿童的初始万古霉素剂量需要比目前的剂量指南高出 35%–65%。结论 ARC 常见于 HSCT 后发热性中性粒细胞减少的儿科患者,导致万古霉素清除率显着增加。我们根据 eGFR、年龄、体重和体温为 HSCT 后发热性中性粒细胞减少症儿童提出了万古霉素给药策略。患有 ARC 的 6 个月至 6 岁儿童的初始万古霉素剂量需要比目前的剂量指南高出 35%–65%。结论 ARC 常见于 HSCT 后发热性中性粒细胞减少的儿科患者,导致万古霉素清除率显着增加。我们根据 eGFR、年龄、体重和体温为 HSCT 后发热性中性粒细胞减少症儿童提出了万古霉素给药策略。
更新日期:2021-08-02
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