Salvador E, Oualha M, Bille E, Beranger A, Moulin F, Benaboud S, Boujaafar S, Gana I, Urien S, Zheng Y, Toubiana J, Briand C, Bustarret O, Geslain G, Renolleau S, Treluyer J-M, Hirt D
Department of Paediatric Intensive Care Unit, Necker Enfants Malades Hospital, Paris Descartes University, Sorbonne-Paris Cité, 149 Rue de Sèvres, 75015, Paris, France; Pharmacology and Drug Evaluation in Children and Pregnant Women EA7323, Paris Descartes University, 27 Rue Du Faubourg Saint Jacques, 75014, Paris, France.
Department of Paediatric Intensive Care Unit, Necker Enfants Malades Hospital, Paris Descartes University, Sorbonne-Paris Cité, 149 Rue de Sèvres, 75015, Paris, France; Pharmacology and Drug Evaluation in Children and Pregnant Women EA7323, Paris Descartes University, 27 Rue Du Faubourg Saint Jacques, 75014, Paris, France.
Clin Microbiol Infect. 2021 Mar;27(3):413-419. doi: 10.1016/j.cmi.2020.04.022. Epub 2020 Apr 29.
Cefazolin is one of curative treatments for infections due to methicillin-sensitive Staphylococcus aureus (MSSA). Both growth and critical illness may impact the pharmacokinetic (PK) parameters. We aimed to build a population PK model for cefazolin in critically ill children in order to optimize individual dosing regimens.
We included all children (age < 18 years, body weight (BW) > 2.5 kg) receiving cefazolin for MSSA infection. Cefazolin total plasma concentrations were quantified by high-performance liquid chromatography. A data modelling process was performed with the software MONOLIX. Monte Carlo simulations were used in order to attain the PK target of 100% fT .
Thirty-nine patients with a median (range) age of 7 (0.1-17) years and a BW of 21 (2.8-79) kg were included. The PK was ascribed to a one-compartment model, where typical clearance and volume of distribution estimations were 1.4 L/h and 3.3 L respectively. BW, according to the allometric rules, and estimated glomerular filtration rate (eGFR) on clearance were the two influential covariates. Continuous infusion with a dosing of 100 mg/kg/day to increase to 150 mg/kg/day for children with a BW < 10 kg or eGFR >200 mL/min/1.73m were the best schemes to reach the PK target of 100% fT.
In critically ill children infected with MSSA, continuous infusion seems to be the most appropriate scheme to reach the PK target of 100 % fT in children with normal and augmented renal function.
头孢唑林是治疗甲氧西林敏感金黄色葡萄球菌（MSSA）感染的有效药物之一。生长发育和危重症状态都可能影响其药代动力学（PK）参数。我们旨在建立危重症儿童头孢唑林的群体PK模型，以优化个体化给药方案。
纳入所有因MSSA感染接受头孢唑林治疗的儿童（年龄<18岁，体重（BW）>2.5 kg）。采用高效液相色谱法定量测定头孢唑林的血浆总浓度。使用MONOLIX软件进行数据建模。采用蒙特卡洛模拟以达到100% fT的PK目标。
纳入39例患者，中位（范围）年龄为7（0.1 - 17）岁，BW为21（2.8 - 79）kg。PK符合一室模型，典型清除率和分布容积估计值分别为1.4 L/h和3.3 L。根据异速生长规则的BW以及清除率方面的估计肾小球滤过率（eGFR）是两个有影响的协变量。对于BW < 10 kg或eGFR > 200 mL/min/1.73m²的儿童，持续输注剂量为100 mg/kg/天并增至150 mg/kg/天是达到100% fT的PK目标的最佳方案。
在感染MSSA的危重症儿童中，持续输注似乎是肾功能正常和增强的儿童达到100% fT的PK目标的最合适方案。
