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Proc Natl Acad Sci U S A. 2017 Sep 26;114(39):10467-10472. doi: 10.1073/pnas.1710235114. Epub 2017 Sep 12.

Network of microbial and antibiotic interactions drive colonization and infection with multidrug-resistant organisms.

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Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109-5680.
Department of Epidemiology, School of Public Health, University of Michigan, Ann Arbor, MI 48109-2029.
Division of Geriatric and Palliative Medicine, University of Michigan, Ann Arbor, MI 48109-2007.
Department of Internal Medicine, University of Michigan Geriatrics, Ann Arbor, MI 48109-2007.
Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109-5680;


The emergence and spread of multidrug-resistant organisms (MDROs) across global healthcare networks poses a serious threat to hospitalized individuals. Strategies to limit the emergence and spread of MDROs include oversight to decrease selective pressure for MDROs by promoting appropriate antibiotic use via antibiotic stewardship programs. However, restricting the use of one antibiotic often requires a compensatory increase in the use of other antibiotics, which in turn selects for the emergence of different MDRO species. Further, the downstream effects of antibiotic treatment decisions may also be influenced by functional interactions among different MDRO species, with the potential clinical implications of such interactions remaining largely unexplored. Here, we attempt to decipher the influence network between antibiotic treatment, MDRO colonization, and infection by leveraging active surveillance and antibiotic treatment data for 234 nursing home residents. Our analysis revealed a complex network of interactions: antibiotic use was a risk factor for primary MDRO colonization, which in turn increased the likelihood of colonization and infection by other MDROs. When we focused on the risk of catheter-associated urinary tract infections (CAUTI) caused by Escherichia coli, Enterococcus, and Staphylococcus aureus we observed that cocolonization with specific pairs of MDROs increased the risk of CAUTI, signifying the involvement of microbial interactions in CAUTI pathogenesis. In summary, our work demonstrates the existence of an underappreciated healthcare-associated ecosystem and strongly suggests that effective control of overall MDRO burden will require stewardship interventions that take into account both primary and secondary impacts of antibiotic treatments.


antibiotics; catheter-associated urinary tract infection; long-term care facilities; multidrug-resistant organisms; nursing homes

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