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Review
. 2017 Apr;30(2):557-596.
doi: 10.1128/CMR.00064-16.

Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

Laurent Poirel  1   2   3 , Aurélie Jayol  4   2   3 , Patrice Nordmann  4   2   3   5
Affiliations
Review

Polymyxins: Antibacterial Activity, Susceptibility Testing, and Resistance Mechanisms Encoded by Plasmids or Chromosomes

Laurent Poirel et al. Clin Microbiol Rev. 2017 Apr.

Abstract

Polymyxins are well-established antibiotics that have recently regained significant interest as a consequence of the increasing incidence of infections due to multidrug-resistant Gram-negative bacteria. Colistin and polymyxin B are being seriously reconsidered as last-resort antibiotics in many areas where multidrug resistance is observed in clinical medicine. In parallel, the heavy use of polymyxins in veterinary medicine is currently being reconsidered due to increased reports of polymyxin-resistant bacteria. Susceptibility testing is challenging with polymyxins, and currently available techniques are presented here. Genotypic and phenotypic methods that provide relevant information for diagnostic laboratories are presented. This review also presents recent works in relation to recently identified mechanisms of polymyxin resistance, including chromosomally encoded resistance traits as well as the recently identified plasmid-encoded polymyxin resistance determinant MCR-1. Epidemiological features summarizing the current knowledge in that field are presented.

Keywords: Gram-negative bacteria; MCR-1; lipopolysaccharide; polymyxins; toxicity.

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Figures

FIG 1
FIG 1
Structures of colistin A and B, colistimethate A and B, and polymyxin B1 and B2.
FIG 2
FIG 2
Overview of the pharmacokinetic pathways for colistimethate (CMS) and colistin (A) and for polymyxin B (B). The thicknesses of the arrows indicate the relative magnitudes of the respective clearance pathways when kidney function is normal. CMS includes fully and all partially methanesulfonated derivatives of colistin. After administration of CMS, extensive renal excretion of the prodrug occurs, with some of the excreted CMS being converted to colistin within the urinary tract. (The figure is based in part on data from reference .)
FIG 3
FIG 3
Regulation pathways of LPS modifications in Klebsiella pneumoniae.
FIG 4
FIG 4
Reports of MCR-1-producing isolates in humans, animals, and both humans and animals.
FIG 5
FIG 5
Outbreaks caused by colistin-resistant, carbapenemase-producing K. pneumoniae isolates. Each star indicates a single report.
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See this image and copyright information in PMC

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