Pharmacology of polymyxins: new insights into an 'old' class of antibiotics.

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Velkov T, Roberts KD, Nation RL, Thompson PE, Li J

Pharmacology of polymyxins: new insights into an 'old' class of antibiotics.

Future Microbiol. 2013 Jun;8(6):711-24. doi: 10.2217/fmb.13.39.

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23701329 [ View in PubMed
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Abstract

Increasing antibiotic resistance in Gram-negative bacteria, particularly in Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae, presents a global medical challenge. No new antibiotics will be available for these 'superbugs' in the near future due to the dry antibiotic discovery pipeline. Colistin and polymyxin B are increasingly used as the last-line therapeutic options for treatment of infections caused by multidrug-resistant Gram-negative bacteria. This article surveys the significant progress over the last decade in understanding polymyxin chemistry, mechanisms of antibacterial activity and resistance, structure-activity relationships and pharmacokinetics/pharmacodynamics. In the 'Bad Bugs, No Drugs' era, we must pursue structure-activity relationship-based approaches to develop novel polymyxin-like lipopeptides targeting polymyxin-resistant Gram-negative 'superbugs'. Before new antibiotics become available, we must optimize the clinical use of polymyxins through the application of pharmacokinetic/pharmacodynamic principles, thereby minimizing the development of resistance.

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