Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou, People's Republic of China.
Key Laboratory of Tropical Diseases Control, Sun Yat-sen University, Ministry of Education, Guangzhou, People's Republic of China.
Emerg Microbes Infect. 2020 Dec;9(1):868-885. doi: 10.1080/22221751.2020.1754133.
Increasing antibiotic resistance in multidrug-resistant (MDR) Gram-negative bacteria (MDR-GNB) presents significant health problems worldwide, since the vital available and effective antibiotics, including; broad-spectrum penicillins, fluoroquinolones, aminoglycosides, and β-lactams, such as; carbapenems, monobactam, and cephalosporins; often fail to fight MDR Gram-negative pathogens as well as the absence of new antibiotics that can defeat these "superbugs". All of these has prompted the reconsideration of old drugs such as polymyxins that were reckoned too toxic for clinical use. Only two polymyxins, polymyxin E (colistin) and polymyxin B, are currently commercially available. Colistin has re-emerged as a last-hope treatment in the mid-1990s against MDR Gram-negative pathogens due to the development of extensively drug-resistant GNB. Unfortunately, rapid global resistance towards colistin has emerged following its resurgence. Different mechanisms of colistin resistance have been characterized, including intrinsic, mutational, and transferable mechanisms.In this review, we intend to discuss the progress over the last two decades in understanding the alternative colistin mechanisms of action and different strategies used by bacteria to develop resistance against colistin, besides providing an update about what is previously recognized and what is novel concerning colistin resistance.
多药耐药（MDR）革兰氏阴性菌（MDR-GNB）中抗生素耐药性的增加在全球范围内带来了重大的健康问题，因为重要的现有且有效的抗生素，包括广谱青霉素、氟喹诺酮类、氨基糖苷类和β-内酰胺类，如碳青霉烯类、单环β-内酰胺类和头孢菌素类；往往无法对抗 MDR 革兰氏阴性病原体，而且也没有新的抗生素可以击败这些“超级细菌”。所有这些都促使人们重新考虑多黏菌素等旧药物，这些药物过去被认为毒性太大，不适合临床使用。目前只有两种多黏菌素，多黏菌素 E（黏菌素）和多黏菌素 B，可在商业上获得。由于广泛耐药性 GNB 的出现，黏菌素在 20 世纪 90 年代中期重新成为治疗 MDR 革兰氏阴性病原体的最后一线希望。不幸的是，在其重新出现后，全球对黏菌素的耐药性迅速出现。已经确定了不同的黏菌素耐药机制，包括内在、突变和可转移机制。在这篇综述中，我们旨在讨论过去二十年在理解替代黏菌素作用机制方面的进展以及细菌对抗黏菌素产生耐药性所采用的不同策略，同时提供有关黏菌素耐药性的最新认识和新认识。
