Microbiome-pathogen interactions drive epidemiological dynamics of antibiotic resistance: A modeling study applied to nosocomial pathogen control

Elife. 2021 Sep 14;10:e68764. doi: 10.7554/eLife.68764.

Abstract

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 modeling 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.

Keywords: C. difficile; E. coli; K. pneumoniae; S. aureus; antibiotics; ecology; epidemiology; global health; human; microbiota; within-host interactions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology
  • Bacteria / drug effects
  • Cross Infection / epidemiology*
  • Cross Infection / microbiology
  • Cross Infection / prevention & control*
  • Drug Resistance, Microbial / drug effects
  • Drug Resistance, Microbial / physiology*
  • Humans
  • Microbiota / drug effects
  • Microbiota / physiology*
  • Models, Theoretical

Substances

  • Anti-Bacterial Agents

Grant support