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The role of “spillover” in antibiotic resistance

View ORCID ProfileScott W. Olesen, View ORCID ProfileMarc Lipsitch, View ORCID ProfileYonatan H. Grad
doi: https://doi.org/10.1101/536714
Scott W. Olesen
1Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115
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Marc Lipsitch
1Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115
2Center for Communicable Disease Dynamics, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115
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Yonatan H. Grad
1Department of Immunology and Infectious Diseases, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115
3Division of Infectious Diseases, Department of Medicine, Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts 02115
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  • For correspondence: ygrad@hsph.harvard.edu
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ABSTRACT

Antibiotic use is a key driver of antibiotic resistance. Understanding the quantitative association between antibiotic use and resulting resistance is important for predicting future rates of antibiotic resistance and for designing antibiotic stewardship policy. However, the use-resistance association is complicated by “spillover”, in which one population’s level of antibiotic use affects another population’s level of resistance via the transmission of bacteria between those populations. Spillover is known to have effects at the level of families and hospitals, but it is unclear if spillover is relevant at larger scales. We used mathematical modeling and analysis of observational data to address this question. First, we used dynamical models of antibiotic resistance to predict the effects of spillover. Whereas populations completely isolated from one another do not experience any spillover, we found that if even 1% of interactions are between populations, then spillover may have large consequences: the effect of a change in antibiotic use in one population on antibiotic resistance in that population could be reduced by as much as 50%. Then, we quantified spillover in observational antibiotic use and resistance data from US states and European countries for 3 pathogen-antibiotic combinations, finding that increased interactions between populations were associated with smaller differences in antibiotic resistance between those populations. Thus, spillover may have an important impact at the level of states and countries, which has ramifications for predicting the future of antibiotic resistance, designing antibiotic resistance stewardship policy, and interpreting stewardship interventions.

Competing Interest Statement

The authors have declared no competing interest.

Footnotes

  • https://doi.org/10.5281/zenodo.3909813

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY 4.0 International license.
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Posted June 30, 2020.
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The role of “spillover” in antibiotic resistance
Scott W. Olesen, Marc Lipsitch, Yonatan H. Grad
bioRxiv 536714; doi: https://doi.org/10.1101/536714
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The role of “spillover” in antibiotic resistance
Scott W. Olesen, Marc Lipsitch, Yonatan H. Grad
bioRxiv 536714; doi: https://doi.org/10.1101/536714

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