Pharmacokinetics/pharmacodynamics of colistin and polymyxin B: are we there yet?

Thien B Tran, Tony Velkov, Roger L. Nation, Alan Forrest, Brian T Tsuji, Phillip J Bergen, Jian Li

Research output: Contribution to journalArticleResearchpeer-review

59 Citations (Scopus)

Abstract

The polymyxin antibiotics [colistin and polymyxin B (PMB)] are increasingly used as a last-line option for the treatment of infections caused by extensively drug-resistant Gram-negative bacteria. Despite having similar structures and antibacterial activity in vitro, the two clinically available polymyxins have very different pharmacological properties, as colistin (polymyxin E) is intravenously administered to patients in the form of an inactive prodrug colistin methanesulphonate (sodium). This review will discuss recent progress in the pharmacokinetics/pharmacodynamics and toxicity of colistin and PMB, the factors that affect their pharmacological profiles, and the challenges for the effective use of both polymyxins. Strategies are proposed for optimising their clinical utility based upon the recent pharmacological studies in vitro, in animals and patients. In the ‘Bad Bugs, No Drugs’ era, polymyxins are a critically important component of the antibiotic armamentarium against difficult-to-treat Gram-negative ‘superbugs’. Rational approaches to the use of polymyxins must be pursued to increase their effectiveness and to minimise resistance and toxicity.

Original languageEnglish
Pages (from-to)592-597
Number of pages6
JournalInternational Journal of Antimicrobial Agents
Volume48
Issue number6
DOIs
Publication statusPublished - 1 Dec 2016

Keywords

  • Nephrotoxicity
  • Pharmacodynamics
  • Pharmacokinetics
  • Polymyxins

Cite this