Pharmacology of polymyxins: New insights into an 'old' class of antibiotics

Tony Velkov, Kade Douglas Roberts, Roger Leigh Nation, Philip Thompson, Jian Li

Research output: Contribution to journalArticleResearchpeer-review

240 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)711 - 724
Number of pages14
JournalFuture Microbiology
Volume8
Issue number6
DOIs
Publication statusPublished - 2013

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