Clinical Review State of the Art Review

Antibiotic resistance in Enterobacteriaceae: mechanisms and clinical implications

BMJ 2016; 352 doi: https://doi.org/10.1136/bmj.h6420 (Published 08 February 2016) Cite this as: BMJ 2016;352:h6420
  1. Jon Iredell, professor/director1,
  2. Jeremy Brown, microbiology registrar2,
  3. Kaitlin Tagg, PhD candidate1
  1. 1Westmead Institute for Medical Research, University of Sydney and Marie Bashir Institute, Sydney, NSW, Australia
  2. 2Department of Microbiology, Institute of Clinical Pathology and Medical Research, Sydney
  1. Correspondence to: J Iredell jonathan.iredell{at}sydney.edu.au

Abstract

Resistance of the Enterobacteriaceae to antibiotics, especially of the β lactam type, is increasingly dominated by the mobilization of continuously expressed single genes that encode efficient drug modifying enzymes. Strong and ubiquitous selection pressure has seemingly been accompanied by a shift from “natural” resistance, such as inducible chromosomal enzymes, membrane impermeability, and drug efflux, to the modern paradigm of mobile gene pools that largely determine the epidemiology of modern antibiotic resistance. In this way, antibiotic resistance is more available than ever before to organisms such as Escherichia coli and Klebsiella pneumoniae that are important causes of major sepsis. Modulation of the phenotype by host bacteria makes gene transmission less obvious and may in part explain why tracking and control of carbapenem resistance has been particularly problematic in the Enterobacteriaceae. This review discusses the underlying principles and clinical implications of the mobility and fixation of resistance genes and the exploitable opportunities and potential threats arising from apparent limitations on diversity in these mobile gene pools. It also provides some illustrative paradoxes and clinical corollaries, as well as a summary of future options.

Footnotes

  • Thanks to Mikala Wang for critical reading of the manuscript.

  • Contributors: JI, JB, and KT reviewed the literature, developed the tables and figures, and wrote the article. JI is guarantor.

  • Competing interests: We have read and understood BMJ policy on declaration of interests and declare the following interests: none.

  • Provenance and peer review: Commissioned; externally peer reviewed.

  • The BMJ did not request patient input on this article when it was commissioned.

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