Antibiotic resistance breakers: current approaches and future directions

FEMS Microbiol Rev. 2019 Sep 1;43(5):490-516. doi: 10.1093/femsre/fuz014.

Abstract

Infections of antibiotic-resistant pathogens pose an ever-increasing threat to mankind. The investigation of novel approaches for tackling the antimicrobial resistance crisis must be part of any global response to this problem if an untimely reversion to the pre-penicillin era of medicine is to be avoided. One such promising avenue of research involves so-called antibiotic resistance breakers (ARBs), capable of re-sensitising resistant bacteria to antibiotics. Although some ARBs have previously been employed in the clinical setting, such as the β-lactam inhibitors, we posit that the broader field of ARB research can yet yield a greater diversity of more effective therapeutic agents than have been previously achieved. This review introduces the area of ARB research, summarises the current state of ARB development with emphasis on the various major classes of ARBs currently being investigated and their modes of action, and offers a perspective on the future direction of the field.

Keywords: ESKAPEE; antibiotic resistance breakers; beta-lactamase inhibitors; combination therapy; efflux pump inhibitors; membrane permeabilisers.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Bacteria / drug effects*
  • Bacterial Infections / drug therapy
  • Biomedical Research / trends*
  • Clinical Trials as Topic
  • Drug Discovery / trends
  • Drug Resistance, Microbial / drug effects*
  • Humans
  • Mice
  • beta-Lactamase Inhibitors / pharmacology
  • beta-Lactamase Inhibitors / therapeutic use

Substances

  • Anti-Bacterial Agents
  • beta-Lactamase Inhibitors