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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.

Original publication

DOI

10.7554/eLife.68764

Type

Journal

Elife

Publication Date

14/09/2021

Volume

10

Keywords

C. difficile, E. coli, K. pneumoniae, S. aureus, antibiotics, ecology, epidemiology, global health, human, microbiota, within-host interactions, Anti-Bacterial Agents, Bacteria, Cross Infection, Drug Resistance, Microbial, Humans, Microbiota, Models, Theoretical