Mechanisms of Bacteroides fragilis resistance to metronidazole

Infect Genet Evol. 2018 Oct:64:156-163. doi: 10.1016/j.meegid.2018.06.020. Epub 2018 Jun 21.

Abstract

Metronidazole-resistant Bacteroides fragilis (B. fragilis) have been reported worldwide. Several mechanisms contribute to B. fragilis resistance to metronidazole. In some cases, the mechanisms of metronidazole resistance are unknown. Understanding the mechanisms of resistance is important for therapy, the design of new alternative drugs, and control of resistant strains. In this study, a comprehensive review of the B. fragilis resistance mechanisms to metronidazole was prepared. The rate of metronidazole-resistant B. fragilis has been reported as ranging from 0.5% to 7.8% in many surveys. According to CLSI, isolates with MICs ≥32 μg/mL are considered to be metronidazole-resistant. In the majority of cases, metronidazole resistance in B. fragilis is coupled with the existence of nim genes. Metronidazole resistance could be induced in nim-negative strains by exposure to sub-MIC levels of metronidazole. There are multi-drug efflux pumps in B. fragilis which can pump out a variety of substrates such as metronidazole. The recA overexpression and deficiency of feoAB are other reported metronidazole resistance mechanisms in this bacterium.

Keywords: Bacteroides fragilis; Mechanisms; Metronidazole; Resistance.

Publication types

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

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Anti-Bacterial Agents / therapeutic use
  • Bacteroides Infections / drug therapy
  • Bacteroides Infections / microbiology
  • Bacteroides fragilis / drug effects*
  • Bacteroides fragilis / genetics
  • Drug Resistance, Bacterial*
  • Gene Expression Regulation, Bacterial
  • Genes, Bacterial
  • Humans
  • Metronidazole / pharmacology*
  • Microbial Sensitivity Tests

Substances

  • Anti-Bacterial Agents
  • Metronidazole