In This Article Expand or collapse the "in this article" section Evolution of Antibiotic Resistance

  • Introduction
  • Overviews
  • History
  • Evolutionary Origins of Antibiotic Resistance Genes
  • Mechanisms of Antibiotic Resistance
  • Epidemiological Emergence of Antibiotic Resistance
  • Hospital-Associated Resistance
  • Roles of Agricultural and Domestic Animals
  • Contaminated Environments as a Reservoir of Antibiotic Resistance
  • Fitness Costs and Reversibility of Antibiotic Resistance
  • Prospects for New Antibiotics
  • General Guidelines for Controlling Resistance
  • Controlling Resistance by Adjusting Antibiotic Treatment
  • Reducing the Need for Antibiotic Treatment
  • Economic Approaches to Control of Antibiotic Resistance

Evolutionary Biology Evolution of Antibiotic Resistance
Paul Ewald
  • LAST REVIEWED: 12 August 2022
  • LAST MODIFIED: 28 August 2018
  • DOI: 10.1093/obo/9780199941728-0113


Antibiotics are defined as chemical compounds that kill or inhibit the growth of bacteria when used in low concentrations. They have been used therapeutically to cure bacterial diseases since the introduction of sulfa drugs in the 1930s, but most effectively since the introduction of penicillin in the 1940s. During the ensuing decades health scientists increasingly recognized that antibiotic treatment leads to evolutionary increases in resistance. This recognition represents the first widespread influence of evolutionary thinking on medical practice. During the past fifty years the effectiveness of antibiotics has deteriorated broadly, leading researchers to develop a comprehensive understanding of the evolution of antibiotic resistance and options for curbing it.


Since the 1960s, mainstream analyses have recognized that antimicrobial resistance is a global problem, exacerbated by different processes in different regions (Neu 1992; O’Neill 2014–2016; Friedman, et al. 2016). In resource-rich countries, it is fueled in hospitals, private practice, and agricultural settings (Lappé 1982, Levy 2002). In resource poor countries, in addition to these influences, resistance is exacerbated by the availability of antimicrobials without prescription (Choffnes, et al. 2010). In rich and poor countries alike, the evolution of antimicrobial resistance involves a conflict of interest between the value of antimicrobials to treated individuals and the costs to the population that arise from the consequent evolution of antimicrobial resistance (Hardin 1968, Baquero and Campos 2003). Mainstream assessments generally focus on evolutionary processes as the cause of the problem, but not as part of the solution (Chadwick and Goode 1997, Bergstrom and Feldgarden 2008). Suggestions for courses of action therefore generally rely on more prudent use of antimicrobials than on innovative ways to incorporate evolutionary processes as part of the solution (Choffnes, et al. 2010).

  • Baquero, F., and J. Campos. 2003. The tragedy of the commons in antimicrobial chemotherapy. Revista Espanola de Quimioterapia 16.1: 11–13.

    Presents the connections between the evolution of antibiotic resistance and the conflict between the short-term benefit of antibiotics to individual patients and the long-term cost of antibiotic resistance to the population.

  • Bergstrom, C. T., and M. Feldgarden. 2008. The ecology and evolution of antibiotic-resistant bacteria. In Evolution in health and disease. Edited by S. C. Stearns and J. C. Koella, 125–137. New York: Oxford Univ. Press.

    An overview of the antibiotic resistance problem within a framework based on ecological and evolutionary principles.

  • Chadwick, D. J., and J. Goode, eds. 1997. Antibiotic resistance: Origins, evolution, selection, and spread. Papers presented at Symposium on Antibiotic Resistance, held at the Ciba Foundation, London, 16–18 July 1996. CIBA Foundation Symposium 207. New York: Wiley.

    A collection of articles by experts on antibiotic resistance, with a broad incorporation of perspectives that had been brought to bear on the problem at the end of the 20th century.

  • Choffnes, E. R., D. A. Relman, and A. Mack. 2010. Antibiotic resistance: Implications for global health and novel intervention strategies: Workshop summary. Washington, DC: National Academies Press.

    Generated from a workshop sponsored by the US Institute of Medicine, this book addresses possible strategies for control of resistance, including alternative treatments, incentives for altering use of antimicrobials, and the development of new antimicrobials.

  • Friedman, N. D., E. Temkin, and Y. Carmeli. 2016. The negative impact of antibiotic resistance. Clinical Microbiology and Infection 22.5: 416–422.

    DOI: 10.1016/j.cmi.2015.12.002

    An overview of negative effects of antibiotic resistance.

  • Hardin, G. 1968. The tragedy of the commons. Science 162.3859: 1243–1248.

    DOI: 10.1126/science.162.3859.1243

    Presents the conflict between actions that are beneficial to individuals in the short term (e.g., antibiotic treatment) and outcomes that are suboptimal to the group as a whole in the long term (e.g., antibiotic resistance).

  • Lappé, M. 1982. Germs that won’t die: Medical consequences of the misuse of antibiotics. New York: Anchor.

    An early call to the dangers of antibiotic resistance written for a general audience.

  • Levy, Stuart B. 2002. The antibiotic paradox. Cambridge, MA: Perseus.

    An engaging, overview of the general problem of antibiotic resistance for a general audience.

  • Neu, H. C. 1992. The crisis in antibiotic resistance. Science 257.5073: 1064–1073.

    DOI: 10.1126/science.257.5073.1064

    A seminal paper that helped raise awareness of antibiotic resistance from a medical concern to an impending crisis.

  • O’Neill, J. (chair). 2014–2016. The review on antimicrobial resistance: Tackling drug-resistant infections globally. London: Wellcome Trust and UK Government.

    A collection of reports that address approaches to cope with the problem of antimicrobial resistance, including reduction in the use of antibiotics, use of alternatives to antibiotics, and development of new antibiotics.

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