Selection and evolution of resistance to antimicrobial drugs

IUBMB Life. 2014 Aug;66(8):521-9. doi: 10.1002/iub.1278. Epub 2014 Jun 16.

Abstract

The overuse and misuse of antibiotics over many years has selected a high frequency of resistance among medically important bacterial pathogens. The evolution of resistance is complex, frequently involving multiple genetic alterations that minimize biological fitness costs and/or increase the resistance level. Resistance is selected at very low drug concentrations, such as found widely distributed in the environment, and this selects for resistant mutants with a high fitness. Once resistance with high fitness is established in a community it is very difficult to reduce its frequency. Addressing the problem of resistance is essential if we are to ensure a future where we can continue to enjoy effective medical control of bacterial infections. This will require several actions including the discovery and development of novel antibiotics, the creation of a continuous pipeline of drug discovery, and the implementation of effective global antibiotic stewardship to reduce the misuse of antibiotics and their release into the environment.

Keywords: antibiotic; evolution; fitness; fluoroquinolone; resistance; rifampicin; sub-MIC.

Publication types

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

MeSH terms

  • Anti-Infective Agents*
  • Biological Evolution*
  • Drug Discovery / methods
  • Drug Discovery / trends
  • Drug Resistance, Bacterial / genetics*
  • Europe
  • Genetic Fitness / genetics*
  • Inappropriate Prescribing / statistics & numerical data
  • Inappropriate Prescribing / trends
  • Microbial Sensitivity Tests
  • Models, Biological*
  • Selection, Genetic / genetics*

Substances

  • Anti-Infective Agents