Department of Pharmacology and Therapeutics, University of Melbourne, Melbourne, Australia.
Medicinal Chemistry, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, Australia.
Adv Exp Med Biol. 2019;1145:15-36. doi: 10.1007/978-3-030-16373-0_3.
Polymyxins are naturally occurring cyclic lipopeptides that were discovered more than 60 years ago. They have a narrow antibacterial spectrum, which is mainly against Gram-negative pathogens. The dry antibiotic pipeline, together with the increasing incidence of bacterial resistance in the clinic, has been dubbed 'the perfect storm'. This has forced a re-evaluation of 'old' antibiotics, in particular the polymyxins, which retain activity against many multidrug-resistant (MDR) Gram-negative organisms. As a consequence, polymyxin B and colistin (polymyxin E) are now used as the last therapeutic option for infections caused by 'superbugs' such as Pseudomonas aeruginosa, Acinetobacter baumannii, and Klebsiella pneumoniae. This chapter covers the history, chemistry and antibacterial spectrum of these very important last-line lipopeptide antibiotics.
多黏菌素是一种天然存在的环状脂肽，于 60 多年前被发现。它们的抗菌谱较窄，主要针对革兰氏阴性病原体。干燥的抗生素流水线，加上临床上细菌耐药性的不断增加，被称为“完美风暴”。这迫使人们重新评估“老”抗生素，特别是多黏菌素，它对许多耐多药（MDR）革兰氏阴性菌仍具有活性。因此，多黏菌素 B 和黏菌素（多黏菌素 E）现在被用作治疗铜绿假单胞菌、鲍曼不动杆菌和肺炎克雷伯菌等“超级细菌”引起的感染的最后治疗选择。本章涵盖了这些非常重要的最后一线脂肽抗生素的历史、化学和抗菌谱。
