Centre for Immunobiology, Blizard Institute, Queen Mary University of London, London, UK.
Royal Free London NHS Foundation Trust, London, UK.
J Antimicrob Chemother. 2019 Apr 1;74(4):961-969. doi: 10.1093/jac/dky524.
The potential for synergy between colistin and fusidic acid in the treatment of MDR Acinetobacter baumannii has recently been shown. The aim of this study was to perform an extensive in vitro characterization of this effect using pharmacokinetic-pharmacodynamic modelling (PKPD) of time-kill experiments in order to estimate clinical efficacy.
For six clinical strains, 312 individual time-kill experiments were performed including 113 unique pathogen-antimicrobial combinations. A wide range of concentrations (0.25-8192 mg/L for colistin and 1-8192 mg/L for fusidic acid) were explored, alone and in combination. PKPD modelling sought to quantify synergistic effects.
A PKPD model confirmed synergy in that colistin EC50 was found to decrease by 83% in the presence of fusidic acid, and fusidic acid maximum increase in killing rate (Emax) also increased 58% in the presence of colistin. Simulations indicated, however, that at clinically achievable free concentrations, the combination may be bacteriostatic in colistin-susceptible strains, but growth inhibition probability was <20% in a colistin-resistant strain.
Fusidic acid may be a useful agent to add to colistin in a multidrug combination for MDR Acinetobacter baumannii.
最近已经证明，多黏菌素和夫西地酸在治疗耐多药鲍曼不动杆菌方面具有协同作用。本研究的目的是通过时间杀伤实验的药代动力学-药效学建模（PKPD）对这种作用进行广泛的体外表征，以估计临床疗效。
对 6 株临床菌株进行了 312 次单独的时间杀伤实验，包括 113 种独特的病原体-抗菌组合。研究探索了广泛的浓度范围（多黏菌素为 0.25-8192mg/L，夫西地酸为 1-8192mg/L），单独使用和联合使用。PKPD 模型旨在量化协同作用。
PKPD 模型证实了协同作用，即在夫西地酸存在的情况下，多黏菌素 EC50 降低了 83%，并且在多黏菌素存在的情况下，夫西地酸的最大杀菌率（Emax）也增加了 58%。然而，模拟表明，在临床可达到的游离浓度下，该组合在多黏菌素敏感株中可能是抑菌的，但在多黏菌素耐药株中，生长抑制的概率<20%。
夫西地酸可能是多黏菌素联合治疗耐多药鲍曼不动杆菌的一种有用药物。
