Combination therapy with polymyxin B and netropsin against clinical isolates of multidrug-resistant Acinetobacter baumannii.
Combination therapy with polymyxin B and netropsin against clinical isolates of multidrug-resistant Acinetobacter baumannii.
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DOI：
10.1038/srep28168
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发表时间：
2016-06-16
影响因子：
4.6
通讯作者：
Ryu CM
中科院分区：
文献类型：
--
作者：
Chung JH;Bhat A;Kim CJ;Yong D;Ryu CM
多粘菌素是治疗革兰氏阴性菌感染的最后手段抗生素。然而，最近出现的多粘菌素耐药细菌迫切需要临床优化多粘菌素的使用，以尽量减少进一步的耐药性演变。在这项研究中，我们开发了一种新的联合治疗使用最低浓度的多粘菌素B。经过对链霉菌次级代谢产物的大规模筛选，我们确定了一种可靠的多粘菌素，并使用高压液相色谱法，核磁共振和质谱法，然后使用各种革兰氏阴性病原菌进行体外测定，确认为netropsin。为了评估多粘菌素B和netropsin在体内联合使用的有效性，我们对感染了粘菌素耐药鲍曼不动杆菌临床分离株以及大肠杆菌、弗氏志贺菌、鼠伤寒沙门氏菌和铜绿假单胞菌的大蜡螟进行了存活分析。感染G.当用多粘菌素B和netropsin组合处理时，大蜡螟的存活率显著高于单独用多粘菌素B或netropsin处理时。我们提出了一种在治疗多重耐药革兰氏阴性菌感染时最大限度地减少多粘菌素B使用的netropsin联合疗法。
Polymyxins are last-resort antibiotics for treating infections of Gram-negative bacteria. The recent emergence of polymyxin-resistant bacteria, however, urgently demands clinical optimisation of polymyxin use to minimise further evolution of resistance. In this study we developed a novel combination therapy using minimal concentrations of polymyxin B. After large-scale screening of Streptomyces secondary metabolites, we identified a reliable polymixin synergist and confirmed as netropsin using high-pressure liquid chromatography, nuclear magnetic resonance, and mass spectrometry followed by in vitro assays using various Gram-negative pathogenic bacteria. To evaluate the effectiveness of combining polymixin B and netropsin in vivo, we performed survival analysis on greater wax moth Galleria mellonella infected with colistin-resistant clinical Acinetobacter baumannii isolates as well as Escherichia coli, Shigella flexineri, Salmonella typhimuruim, and Pseudomonas aeruginosa. The survival of infected G. mellonella was significantly higher when treated with polymyxin B and netropsin in combination than when treated with polymyxin B or netropsin alone. We propose a netropsin combination therapy that minimises the use of polymyxin B when treating infections with multidrug resistant Gram-negative bacteria.