Bedenić Branka, Beader Natasa, Godič-Torkar Karmen, Prahin Esmina, Mihaljević Ljiljana, Ćačić Marko, Vraneš Jasmina
a Department of Microbiology , School of Medicine, University of Zagreb , Croatia.
b Department of Clinical and Molecular Microbiology , Clinical Hospital Center Zagreb , Croatia.
J Chemother. 2016 Oct;28(5):375-82. doi: 10.1179/1973947815Y.0000000062. Epub 2016 Jul 22.
Previous studies found short postantibiotic effect of colistin on Acinetobacter baumannii. Many studies have evaluated the potential for synergy between colistin and other antibiotics against A. baumannii. The aim of this study was to determine in vitro synergy and postantibiotic effect (PAE) of colistin alone and combined with other antibiotics (vancomycin or meropenem) against eight carbapenem-non-susceptible Acinetobacter spp. strains with defined resistance mechanisms. It was hypothesised that vancomycin or meropenem would prologue the PAE of colistin since it was previously found that they exert synergism with colistin in time-kill kinetics and chequerboard analysis. After exposure of 1 hour colistin alone exhibited the negative ( - 0.07 hour) (OXA-143), short (0.2-1.82 hours) (OXA-24, OXA-58, OXA-72, VIM-1+OXA-23, OXA-58+NDM-1, ISAba1/OXA-69) or moderate PAE (3.2 hours) for OXA-23 positive strain. When combined with vancomycin, the PAE was moderate (1.7-4 hours) with OXA-23, OXA-23+VIM-1, OXA-72 and OXA-24 positive strains while with OXA-58, OXA-143, OXA-58/NDM-1 and ISAba1/OXA-69 positive strains, it was not possible to calculate mean duration of PAE because there was no regrowth after exposure to antibiotics or it was longer than 5 hours. The combination with meropenem resulted in short (0.2 hours) (OXA-143), moderate (2.4-3.73 hours) (OXA-24, OXA-58, OXA-23, OXA-23+VIM-1), long PAE of 5 hours (OXA-23) or longer than 5 hours (OXA-58+VIM-1, ISAba1/OXA-69). From the clinical point of view, the prolongation of colistin PAE when combined with other antibiotics could provide a rationale for the modification of the dosing interval and could be important for the optimization of the treatment regimen and the minimization of drug-induced side effects.
先前的研究发现，黏菌素对鲍曼不动杆菌的抗生素后效应较短。许多研究评估了黏菌素与其他抗生素联合针对鲍曼不动杆菌的协同作用潜力。本研究的目的是确定黏菌素单独及与其他抗生素（万古霉素或美罗培南）联合对8株具有明确耐药机制的碳青霉烯不敏感不动杆菌属菌株的体外协同作用及抗生素后效应（PAE）。据推测，万古霉素或美罗培南会延长黏菌素的PAE，因为先前发现在时间杀菌动力学和棋盘分析中它们与黏菌素发挥协同作用。单独暴露1小时后，黏菌素对OXA - 143菌株表现出负的（ - 0.07小时）PAE，对OXA - 24、OXA - 58、OXA - 72、VIM - 1 + OXA - 23、OXA - 58 + NDM - 1、ISAba1/OXA - 69菌株表现出短的（0.2 - 1.82小时）PAE，对OXA - 23阳性菌株表现出中等的（3.2小时）PAE。当与万古霉素联合时，对于OXA - 23、OXA - 23 + VIM - 1、OXA - 72和OXA - 24阳性菌株，PAE为中等（1.7 - 4小时），而对于OXA - 58、OXA - 143、OXA - 58/NDM - 1和ISAba1/OXA - 69阳性菌株，由于暴露于抗生素后没有再生长或超过5小时，无法计算PAE的平均持续时间。与美罗培南联合导致对OXA - 143菌株的PAE短（0.2小时），对OXA - 24、OXA - 58、OXA - 23、OXA - 23 + VIM - 1菌株的PAE中等（2.4 - 3.73小时），对OXA - 23菌株的PAE长为5小时，对OXA - 58 + VIM - 1、ISAba1/OXA - 69菌株的PAE超过5小时。从临床角度来看，黏菌素与其他抗生素联合时PAE的延长可为调整给药间隔提供理论依据，对于优化治疗方案及最小化药物诱导的副作用可能很重要。
