How competition governs whether moderate or aggressive treatment minimizes antibiotic resistance

  1. C Colijn  Is a corresponding author
  2. T Cohen
  1. Imperial College London, United Kingdom
  2. Yale University, United States

Abstract

Understanding how our use of antimicrobial drugs shapes future levels of drug resistance is crucial. Recently there has been debate over whether an aggressive (i.e. high dose) or more moderate (i.e. lower dose) treatment of individuals will most limit the emergence and spread of resistant bacteria. Here we demonstrate how one can understand and resolve these apparently contradictory conclusions. We show that a key determinant of which treatment strategy will perform best at the individual level is the extent of effective competition between resistant and sensitive pathogens within a host. We extend our analysis to the community level, exploring the spectrum between strict inter-strain competition and strain independence. From this perspective as well, we find that the magnitude of effective competition between resistant and sensitive strains determines whether an aggressive approach or moderate approach minimizes the burden of resistance in the population.

Article and author information

Author details

  1. C Colijn

    Department of Mathematics, Imperial College London, London, United Kingdom
    For correspondence
    c.colijn@imperial.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
  2. T Cohen

    School of Public Health, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Michael Doebeli, University of British Columbia, Canada

Version history

  1. Received: August 3, 2015
  2. Accepted: September 18, 2015
  3. Accepted Manuscript published: September 22, 2015 (version 1)
  4. Accepted Manuscript updated: September 25, 2015 (version 2)
  5. Version of Record published: November 11, 2015 (version 3)

Copyright

© 2015, Colijn & Cohen

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. C Colijn
  2. T Cohen
(2015)
How competition governs whether moderate or aggressive treatment minimizes antibiotic resistance
eLife 4:e10559.
https://doi.org/10.7554/eLife.10559

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https://doi.org/10.7554/eLife.10559

Further reading

  1. A mathematical model has been used to explore different approaches to minimizing antibiotic resistance.

    1. Ecology
    2. Epidemiology and Global Health
    Aleksandra Kovacevic, David RM Smith ... Lulla Opatowski
    Research Article

    Non-pharmaceutical interventions implemented to block SARS-CoV-2 transmission in early 2020 led to global reductions in the incidence of invasive pneumococcal disease (IPD). By contrast, most European countries reported an increase in antibiotic resistance among invasive Streptococcus pneumoniae isolates from 2019 to 2020, while an increasing number of studies reported stable pneumococcal carriage prevalence over the same period. To disentangle the impacts of the COVID-19 pandemic on pneumococcal epidemiology in the community setting, we propose a mathematical model formalizing simultaneous transmission of SARS-CoV-2 and antibiotic-sensitive and -resistant strains of S. pneumoniae. To test hypotheses underlying these trends five mechanisms were built into the model and examined: (1) a population-wide reduction of antibiotic prescriptions in the community, (2) lockdown effect on pneumococcal transmission, (3) a reduced risk of developing an IPD due to the absence of common respiratory viruses, (4) community azithromycin use in COVID-19 infected individuals, (5) and a longer carriage duration of antibiotic-resistant pneumococcal strains. Among 31 possible pandemic scenarios involving mechanisms individually or in combination, model simulations surprisingly identified only two scenarios that reproduced the reported trends in the general population. They included factors (1), (3), and (4). These scenarios replicated a nearly 50% reduction in annual IPD, and an increase in antibiotic resistance from 20% to 22%, all while maintaining a relatively stable pneumococcal carriage. Exploring further, higher SARS-CoV-2 R0 values and synergistic within-host virus-bacteria interaction mechanisms could have additionally contributed to the observed antibiotic resistance increase. Our work demonstrates the utility of the mathematical modeling approach in unraveling the complex effects of the COVID-19 pandemic responses on AMR dynamics.