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J Antimicrob Chemother. 2013 Jun;68(6):1213-9. doi: 10.1093/jac/dkt039. Epub 2013 Feb 13.

Novel derivatives of polymyxins.

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Division of Clinical Microbiology, Helsinki University Hospital, FI-00029 HUSLAB, Helsinki, Finland.


Polymyxin B and colistin (polymyxin E) are bactericidal pentacationic lipopeptides that act specifically on Gram-negative bacteria, first by disrupting their outermost permeability barrier, the outer membrane (OM), and then damaging the cytoplasmic membrane. Both were discovered in the mid-1950s and subsequently used in intravenous therapy, but soon largely abandoned because of nephrotoxicity. The emergence of extremely multiresistant strains has now forced clinicians to reinstate them in the therapy of severe infections caused by such strains. This article reviews recent attempts to develop novel derivatives of polymyxins that exhibit less toxicity and greater potency than the existing drugs. In addition, studies of novel des-fatty acyl-polymyxin derivatives that display activity against Pseudomonas aeruginosa are included. The review also covers recent studies of derivatives that lack potent bactericidal action, but which disrupt the OM, which increases bacterial permeability to other antibiotics, facilitating their entry into the cell.


Acinetobacter baumannii; Escherichia coli; Klebsiella pneumoniae; NAB739; Pseudomonas aeruginosa; des-fatty acyl-polymyxin; nephrotoxicity

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