University of Queensland Centre for Clinical Research, Faculty of Medicine, The University of Queensland, Brisbane, Queensland, Australia.
Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.
J Antimicrob Chemother. 2019 Jun 1;74(6):1662-1669. doi: 10.1093/jac/dkz069.
Patients with septic shock may undergo extensive physiological alterations that can alter antibiotic pharmacokinetics.
To describe the population pharmacokinetics of ciprofloxacin in septic shock and to define recommendations for effective ciprofloxacin dosing in these patients.
Adult patients with septic shock treated with ciprofloxacin were eligible for inclusion. Concentrations were measured by HPLC-MS/MS. Population pharmacokinetic modelling was performed with Monte Carlo simulations then used to define dosing regimens that optimize the PTA of an AUC/MIC ratio >125 for different MICs and fractional target attainment (FTA) of empirical and targeted therapy against Pseudomonas aeruginosa.
We included 48 patients with median Simplified Acute Physiology Score (SAPS) II of 49 and 90 day mortality of 33%. Ciprofloxacin pharmacokinetics was best described by a two-compartment linear model including CLCR and body weight as covariates on CL and central volume respectively. With a dose of 400 mg q8h and CLCR of 80 mL/min, >95% PTA was achieved for bacteria with MICs ≤0.25 mg/L. For empirical treatment of P. aeruginosa, 600 mg q8h only reached a maximum of 68% FTA. For directed therapy against P. aeruginosa, a dose of 600 mg q8h was needed to achieve sufficient AUC/MIC ratios.
In patients with septic shock, standard ciprofloxacin dosing achieved concentrations to successfully treat bacteria with MICs ≤0.25 mg/L and then only in patients with normal or reduced CLCR. To cover pathogens with higher MICs or in patients with augmented renal CL, doses may have to be increased.
脓毒症休克患者可能经历广泛的生理改变，从而改变抗生素的药代动力学。
描述环丙沙星在脓毒症休克患者中的群体药代动力学，并确定这些患者有效环丙沙星给药的建议。
符合纳入标准的是接受环丙沙星治疗的脓毒症休克成年患者。采用高效液相色谱-串联质谱法（HPLC-MS/MS）测定浓度。采用蒙特卡罗模拟法进行群体药代动力学建模，然后用于定义不同 MIC 和经验性和靶向治疗对铜绿假单胞菌的 AUC/MIC 比值>125 的目标治疗概率（PTA）和目标达到率（FTA）的优化给药方案。
共纳入 48 例患者，简化急性生理学评分（SAPS）Ⅱ中位数为 49 分，90 天死亡率为 33%。环丙沙星药代动力学最好用一个两室线性模型来描述，该模型包括 CLCR 和体重，分别作为 CL 和中央容积的协变量。当剂量为 400mg，q8h 且 CLCR 为 80mL/min 时，MICs≤0.25mg/L 的细菌可达到>95%的 PTA。对于铜绿假单胞菌的经验性治疗，600mg，q8h 仅达到 68%的最大 FTA。对于铜绿假单胞菌的靶向治疗，需要 600mg，q8h 的剂量才能达到足够的 AUC/MIC 比值。
在脓毒症休克患者中，标准的环丙沙星剂量可达到成功治疗 MICs≤0.25mg/L 的细菌的浓度，然后仅在 CLCR 正常或降低的患者中达到。为了覆盖 MIC 较高的病原体或 CLCR 增加的患者，可能需要增加剂量。
