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Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora

View ORCID ProfileChristine Tedijanto, View ORCID ProfileScott W. Olesen, View ORCID ProfileYonatan H. Grad, View ORCID ProfileMarc Lipsitch
doi: https://doi.org/10.1101/288704
Christine Tedijanto
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, Massachusetts, 02115, USA;
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Scott W. Olesen
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts, 02115, USA;
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Yonatan H. Grad
Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts, 02115, USA;Division of Infectious Diseases, Brigham and Women’s Hospital, Harvard Medical School, 15 Francis Street, Boston, Massachusetts, 02115, USA
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Marc Lipsitch
Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard T.H. Chan School of Public Health, 677 Huntington Avenue, Boston, Massachusetts, 02115, USA;Department of Immunology and Infectious Diseases, Harvard T.H. Chan School of Public Health, 655 Huntington Avenue, Boston, Massachusetts, 02115, USA;
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Abstract

Bystander selection ‐ the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment ‐ is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic-species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen (“proportion of bystander exposures”). Data sources include the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey (NAMCS/NHAMCS), the Human Microbiome Project, and additional carriage and etiological data from existing literature. For outpatient prescribing in the United States, we find that this proportion over all included antibiotic classes is over 80% for 8 of 9 organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or concentrated prescribing of a particular antibiotic for conditions caused by the species of interest. Applying our results, we roughly estimate that pneumococcal conjugate vaccination programs result in nearly the same proportional reduction in total antibiotic exposures of S. pneumoniae, S. aureus, and E. coli, despite the latter two organisms not being targeted by the vaccine. These results underscore the importance of considering antibiotic exposures of bystanders, in addition to the target pathogen, in measuring the impact of antibiotic resistance interventions.

Significance Statement Bystander selection, defined as the inadvertent pressure imposed by antibiotic treatment on microbes other than the targeted pathogen, is hypothesized to be a major factor in the propagation of antibiotic resistance, but its extent has not been characterized. We estimate the proportion of bystander exposures across a range of antibiotics and potential pathogens commonly found in the normal flora and describe factors driving variability of these proportions. Impact estimates for antibiotic resistance interventions, including vaccination, are often limited to effects on a target pathogen. However, the reduction of antibiotic treatment for conditions caused by one pathogen may have the broader potential to decrease bystander selection pressures for resistance on many other organisms.

Footnotes

  • Corresponding Author: Christine Tedijanto Harvard T.H. Chan School of Public Health, 677 Huntington Ave, Suite 506, Boston, MA 02115. ctedijanto{at}g.harvard.edu

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted September 28, 2018.
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Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora
Christine Tedijanto, Scott W. Olesen, Yonatan H. Grad, Marc Lipsitch
bioRxiv 288704; doi: https://doi.org/10.1101/288704
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Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora
Christine Tedijanto, Scott W. Olesen, Yonatan H. Grad, Marc Lipsitch
bioRxiv 288704; doi: https://doi.org/10.1101/288704

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