1. Ecology
  2. Epidemiology and Global Health
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Microbiome-pathogen interactions drive epidemiological dynamics of antibiotic resistance: a modelling study applied to nosocomial pathogen control

  1. David R M Smith  Is a corresponding author
  2. Laura Temime
  3. Lulla Opatowski
  1. Institut Pasteur, France
  2. Conservatoire national des arts et métiers, France
Research Article
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Cite this article as: eLife 2021;10:e68764 doi: 10.7554/eLife.68764


The human microbiome can protect against colonization with pathogenic antibiotic-resistant bacteria (ARB), but its impacts on the spread of antibiotic resistance are poorly understood. We propose a mathematical modelling framework for ARB epidemiology formalizing within-host ARB-microbiome competition, and impacts of antibiotic consumption on microbiome function. Applied to the healthcare setting, we demonstrate a trade-off whereby antibiotics simultaneously clear bacterial pathogens and increase host susceptibility to their colonization, and compare this framework with a traditional strain-based approach. At the population level, microbiome interactions drive ARB incidence, but not resistance rates, reflecting distinct epidemiological relevance of different forces of competition. Simulating a range of public health interventions (contact precautions, antibiotic stewardship, microbiome recovery therapy) and pathogens (Clostridioides difficile, methicillin-resistant Staphylococcus aureus, multidrug-resistant Enterobacteriaceae) highlights how species-specific within-host ecological interactions drive intervention efficacy. We find limited impact of contact precautions for Enterobacteriaceae prevention, and a promising role for microbiome-targeted interventions to limit ARB spread.

Data availability

Model equations and parameter values are provided in the manuscript, as well as in supporting R files and a Mathematica notebook available online at https://github.com/drmsmith/microbiomeR

Article and author information

Author details

  1. David R M Smith

    Global Health, Institut Pasteur, Paris, France
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-7330-4262
  2. Laura Temime

    MESuRS, Conservatoire national des arts et métiers, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8850-5403
  3. Lulla Opatowski

    Global Health, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.


Agence Nationale de la Recherche (SPHINX-17-CE36-0008-01)

  • David R M Smith

Canadian Institutes of Health Research (Doctoral Foreign Study Award 164263)

  • David R M Smith

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Gwenan M Knight, London School of Hygiene and Tropical Medicine, United Kingdom

Publication history

  1. Received: March 26, 2021
  2. Accepted: August 31, 2021
  3. Accepted Manuscript published: September 14, 2021 (version 1)


© 2021, Smith et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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