Pharmacokinetics/pharmacodynamics of Colistin and Polymyxin B: Are We There Yet?

Overview

Journal Int J Antimicrob Agents

Specialties Infectious Diseases
Pharmacology

Date 2016 Oct 30

PMID 27793510

Citations 76

Authors

Thien B Tran

Tony Velkov

Roger L Nation

Alan Forrest

Brian T Tsuji

Phillip J Bergen

Jian Li

Affiliations

Soon will be listed here.

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.

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