Novel derivatives of polymyxins

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...

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Bibliographic Details
Published in:Journal of antimicrobial chemotherapy 2013-06, Vol.68 (6), p.1213-1219
Main Author: Vaara, Martti
Format: Article
Language:English
Subjects:
Animals
Anti-Bacterial Agents - pharmacology
Anti-Bacterial Agents - therapeutic use
Antibiotics
Antimicrobial agents
Bacteria - drug effects
Bacterial Infections - drug therapy
Bacterial Infections - microbiology
Bacterial Outer Membrane Proteins - metabolism
Drug resistance
Gram-negative bacteria
Humans
Membranes
Polymyxin B - pharmacology
Polymyxin B - therapeutic use
Polymyxins - pharmacology
Polymyxins - therapeutic use
Pseudomonas aeruginosa
Pseudomonas Infections - drug therapy
Pseudomonas Infections - microbiology
Toxicity
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Summary: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.
ISSN:0305-7453
1460-2091
DOI:10.1093/jac/dkt039