The path of least resistance: aggressive or moderate treatment?

Author:

Kouyos Roger D.12,Metcalf C. Jessica E.13,Birger Ruthie1ORCID,Klein Eili Y.14,Abel zur Wiesch Pia5,Ankomah Peter6,Arinaminpathy Nimalan17,Bogich Tiffany L.18,Bonhoeffer Sebastian9,Brower Charles110,Chi-Johnston Geoffrey11,Cohen Ted5,Day Troy12,Greenhouse Bryan13,Huijben Silvie14,Metlay Joshua15,Mideo Nicole16,Pollitt Laura C.171819,Read Andrew F.17188,Smith David L.3,Standley Claire20,Wale Nina1718,Grenfell Bryan18

Affiliation:

1. Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA

2. Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zürich, Zürich, Switzerland

3. Department of Zoology, Oxford University, Oxford, UK

4. Center for Advanced Modeling, Department of Emergency Medicine, Johns Hopkins University, Baltimore, MD, USA

5. Division of Global Health Equity, Brigham and Women's Hospital and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA

6. Department of Biology, Emory University, Atlanta, GA, USA

7. Department of Infectious Disease Epidemiology, Imperial College London, London, UK

8. Fogarty International Center, National Institutes of Health, Bethesda, MD, USA

9. Institute of Integrative Biology ETH Zurich, Zurich, Switzerland

10. Center for Disease Dynamics, Economics & Policy, Washington, DC, USA

11. Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA

12. Departments of Mathematics and Biology, Queen's University, Kingston, Ontario, Canada

13. Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, VA, USA

14. Barcelona Centre for International Health Research, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain

15. General Medicine Division, Massachusetts General Hospital, Boston, MA, USA

16. Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, Ontario, Canada

17. Centre for Infectious Disease Dynamics, The Pennsylvania State University, University Park, State College, PA, USA

18. Departments of Biology and Entomology, The Pennsylvania State University, University Park, State College, PA, USA

19. Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh, UK

20. Department of Health Policy, George Washington University, Washington, DC, USA

Abstract

The evolution of resistance to antimicrobial chemotherapy is a major and growing cause of human mortality and morbidity. Comparatively little attention has been paid to how different patient treatment strategies shape the evolution of resistance. In particular, it is not clear whether treating individual patients aggressively with high drug dosages and long treatment durations, or moderately with low dosages and short durations can better prevent the evolution and spread of drug resistance. Here, we summarize the very limited available empirical evidence across different pathogens and provide a conceptual framework describing the information required to effectively manage drug pressure to minimize resistance evolution.

Publisher

The Royal Society

Subject

General Agricultural and Biological Sciences,General Environmental Science,General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,General Medicine

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