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《工程(英文)》 >> 2022年 第13卷 第6期 doi: 10.1016/j.eng.2020.11.005

临床上重要的革兰阴性菌多黏菌素耐药机制对毒力和适应性的影响

State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China

收稿日期: 2020-07-15 修回日期: 2020-09-20 录用日期: 2021-11-15 发布日期: 2021-01-26

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摘要

随着多重耐药革兰阴性菌(如鲍曼不动杆菌、肺炎克雷伯菌和大肠埃希菌等)的出现,人类正在面临着巨大且日益严重的全球威胁。多黏菌素B和E(黏菌素)是治疗多重耐药革兰阴性菌的最后一线药物。多黏菌素是一种阳离子抗菌肽,能破坏革兰阴性菌的外膜。然而,随着多黏菌素临床应用的日益增多,有关多黏菌素耐药革兰阴性菌的报道也越来越多。多黏菌素耐药机制主要是通过脂多糖(lipopolysaccharide, LPS)的修饰或完全丧失介导的。LPS也是革兰阴性菌的毒力因子,LPS的改变可能与细菌的毒力有关。尽管人们普遍认为获得耐药性会使细菌产生适应性代价,当抗生素选择压力降低时,与耐药相关的适应性代价可能使耐药菌难以与敏感菌竞争,从而很快从群体中被清除。但如果菌株在获得耐药性的同时,适应性和毒力增强将会导致耐药菌株的广泛传播,造成巨大的临床损失。目前一些研究发现,与敏感菌相比,多黏菌素耐药菌具有更高的毒力和更强的适应性。为了预测多黏菌素耐药性的发展并评估缓解多黏菌素耐药性的干预措施,了解多黏菌素耐药菌株与敏感菌株之间的相对生物成本,本文将总结阐述多黏菌素耐药机制对鲍曼不动杆菌、肺炎克雷伯菌和大肠埃希菌毒力和适应性的影响。

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