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Synergistic Activity of Colistin in Combination With Resveratrol Against Colistin-Resistant Gram-Negative Pathogens

机译：Colistin与白藜芦醇联合对Colistin耐药革兰氏阴性病原菌的协同活性

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>Objectives: In this study, we investigated the antimicrobial activity of resveratrol in combination with colistin, a last-resort agent for the treatment of severe infections caused by multidrug resistant Gram-negative pathogens.>Methods: The synergistic activity and the bactericidal activity of colistin in combination with resveratrol was investigated by checkerboard assays and time-kill assays, respectively. A total of 21 strains were investigated, including 16 strains of different species (Klebsiella pneumoniae, n = 6, Escherichia coli, n = 6; Citrobacter braakii, n = 1; Stenotrophomonas malthophilia, n = 1; Enterobacter cloaceae, n = 1; Acinetobacter baumannii, n = 1) with acquired colistin resistance, three colistin-susceptible K. pneumoniae precursors, and two strains of intrinsically colistin-resistant species (Serratia marcescens, n = 1; Proteus mirabilis, n = 1). Mechanisms of acquired colistin resistance included chromosomal mutations (i.e., mgrB, pmrAB) and plasmid genes (mcr-1, mcr-1.2).>Results: Resveratrol did not show any significant intrinsic antimicrobial activity. Overall, a relevant synergistic antimicrobial activity of resveratrol in combination with colistin was observed with all tested strains, except for the three colistin-susceptible K. pneumoniae strains, and for two mcr-1-positive E. coli strains. In time-kill assays, performed with 15 selected strains, the combination of colistin 2 mg/L plus resveratrol 128 mg/L was bactericidal with 11 strains, and bacteriostatic for the remaining ones.>Conclusions: Resveratrol was found to potentiate colistin activity against a wide panel of colistin-resistant strains, regardless of species and resistance mechanisms, which would deserve further investigation for potential clinical applications.
机译：>目的：在这项研究中，我们研究了白藜芦醇联合大肠菌素（一种针对多药耐药革兰氏阴性病原体引起的严重感染的最后治疗剂）的抗菌活性。>方法： 分别通过棋盘试验和时间杀灭试验研究了大黄素与白藜芦醇联合的协同活性和杀菌活性。共调查了21个菌株，包括16个不同物种的菌株（肺炎克雷伯菌，n = 6，大肠杆菌，n = 6；布拉氏柠檬酸杆菌，n = 1；嗜麦芽嗜单胞菌的嗜甲基菌，n = 1；阴沟肠杆菌，n = 1；和鲍曼不动杆菌，n = 1），具有获得性大肠菌素抗性，三种大肠菌素易感性肺炎克雷伯菌前体和两株固有的大肠菌素抗性菌种（粘质沙雷氏菌（Serratia marcescens），n = 1;奇异变形杆菌（Proteus mirabilis），n = 1）。获得性大肠菌素抗性的机制包括染色体突变（即mgrB，pmrAB）和质粒基因（mcr-1，mcr-1.2）。>结果：白藜芦醇未显示任何显着的内在抗菌活性。总体而言，除三种大肠杆菌敏感的肺炎克雷伯菌菌株和两种mcr-1阳性大肠杆菌菌株外，在所有测试菌株中均观察到白藜芦醇与大肠菌素联合具有相关的协同抗菌活性。在对15个选定菌株进行的时间杀灭试验中，粘菌素2 mg / L加白藜芦醇128 mg / L的组合对11个菌株具有杀菌作用，其余菌株具有抑菌作用。>结论：白藜芦醇为研究发现，无论种类和耐药机制如何，大肠菌素耐药菌株均可增强大肠菌素的活性，这对于潜在的临床应用值得进一步研究。

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