Northern Antibiotics Ltd., Eskolantie 1, POB 72, FI-00720 Helsinki, Finland; Division of Clinical Microbiology, Helsinki University Hospital, Haartmaninkatu 3, POB 30, FI-00029 HUSLAB, Helsinki, Finland.
Curr Opin Microbiol. 2010 Oct;13(5):574-81. doi: 10.1016/j.mib.2010.09.002. Epub 2010 Sep 24.
The emerging very multiresistant Gram-negative bacteria cause remarkable therapeutic challenges. There are no novel classes of agents in clinical development for the treatment of Gram-negative infections. Polymyxins (polymyxin B and colistin) were abandoned in the seventies but are now back in the therapy as the last resort. Their nephrotoxicity may complicate the therapy or even necessitate its discontinuation. Less toxic polymyxin derivatives would be highly welcome. Novel derivatives lack in strategic positions two of the five cationic charges of polymyxins, differ from polymyxins in their renal handling and affinity to kidney brush-border membrane, and are in preclinical studies. Less characterized other recent derivatives, also reviewed here, have increased the collective knowledge on the structure-function relationships in polymyxins. Acquired resistance to polymyxins has been encountered. However, the resistance mechanism compromises the function of the bacterial outer membrane as a permeability barrier to other noxious agents.
新兴的非常耐药的革兰氏阴性菌引起了显著的治疗挑战。目前，用于治疗革兰氏阴性感染的新型药物类别尚未在临床开发中。多粘菌素（多粘菌素 B 和粘菌素）在 70 年代被弃用，但现在又回到了治疗的最后手段。它们的肾毒性可能会使治疗复杂化，甚至需要停止治疗。更具毒性的多粘菌素衍生物将受到高度欢迎。新型衍生物在战略位置上缺少多粘菌素的五个阳离子电荷中的两个，在肾脏处理和与肾脏刷状缘膜的亲和力方面与多粘菌素不同，目前正在进行临床前研究。这里也回顾了其他最近的特征不那么明显的衍生物，这些衍生物增加了人们对多粘菌素结构-功能关系的集体认识。已经发现了对多粘菌素的获得性耐药。然而，耐药机制损害了细菌外膜作为其他有害剂的渗透性屏障的功能。
