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

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.

journal_name

Int J Antimicrob Agents

journal_title

International journal of antimicrobial agents

authors

Tran TB,Velkov T,Nation RL,Forrest A,Tsuji BT,Bergen PJ,Li J

doi

10.1016/j.ijantimicag.2016.09.010

subject

Has Abstract

pub_date

2016-12-01 00:00:00

pages

592-597

issue

6

eissn

0924-8579

issn

1872-7913

pii

S0924-8579(16)30282-5

journal_volume

48

pub_type

杂志文章,评审

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