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

eLife

Lulla Opatowski¹  David RM Smith²  Laura Temime³ 

[1]Institut Pasteur, Epidemiology and Modelling of Antibiotic Evasion (EMAE), Paris, France

[2]Université Paris-Saclay, UVSQ, Inserm, CESP, Anti-infective evasion and pharmacoepidemiology team, Montigny-Le-Bretonneux, France

[3]Institut Pasteur, Epidemiology and Modelling of Antibiotic Evasion (EMAE), Paris, France

[4]Université Paris-Saclay, UVSQ, Inserm, CESP, Anti-infective evasion and pharmacoepidemiology team, Montigny-Le-Bretonneux, France

[5]Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire national des arts et métiers, Paris, France

[6]Modélisation, épidémiologie et surveillance des risques sanitaires (MESuRS), Conservatoire national des arts et métiers, Paris, France

[7]PACRI unit, Institut Pasteur, Conservatoire national des arts et métiers, Paris, France

关键词: S. aureus;    K. pneumoniae;    C. difficile;    microbiota;    within-host interactions;    antibiotics;    E. coli;    Human;    Other;   

DOI  :  10.7554/eLife.68764

来源: eLife Sciences Publications, Ltd

【 摘 要 】

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.

【 授权许可】

CC BY