title: The path of least resistance: aggressive or moderate treatment?
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.
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA Division of Infectious Diseases and Hospital Epidemiology, University Hospital Zürich, University of Zürich, Zürich, Switzerland.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Kouyos
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA Department of Zoology, Oxford University, Oxford, UK.
authors.forename: C Jessica E
authors.initials: CJ
authors.lastname: Metcalf
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA rbirger@princeton.edu.
authors.forename: Ruthie
authors.identifier: http://orcid.org/0000-0002-2960-5084
authors.initials: R
authors.lastname: Birger
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA Center for Advanced Modeling, Department of Emergency Medicine, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Eili Y
authors.initials: EY
authors.lastname: Klein
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Pia
authors.initials: P
authors.lastname: Abel zur Wiesch
authors.affiliation: Department of Biology, Emory University, Atlanta, GA, USA.
authors.forename: Peter
authors.initials: P
authors.lastname: Ankomah
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA Department of Infectious Disease Epidemiology, Imperial College London, London, UK.
authors.forename: Nimalan
authors.initials: N
authors.lastname: Arinaminpathy
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Tiffany L
authors.initials: TL
authors.lastname: Bogich
authors.affiliation: Institute of Integrative Biology ETH Zurich, Zurich, Switzerland.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Bonhoeffer
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA Center for Disease Dynamics, Economics & Policy, Washington, DC, USA.
authors.forename: Charles
authors.initials: C
authors.lastname: Brower
authors.affiliation: Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD, USA.
authors.forename: Geoffrey
authors.initials: G
authors.lastname: Chi-Johnston
authors.affiliation: Division of Global Health Equity, Brigham and Women's Hospital and Department of Epidemiology, Harvard School of Public Health, Boston, MA, USA.
authors.forename: Ted
authors.initials: T
authors.lastname: Cohen
authors.affiliation: Departments of Mathematics and Biology, Queen's University, Kingston, Ontario, Canada.
authors.forename: Troy
authors.initials: T
authors.lastname: Day
authors.affiliation: Department of Medicine, Division of Infectious Diseases, University of California, San Francisco, VA, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Greenhouse
authors.affiliation: Barcelona Centre for International Health Research, Hospital Clínic, Universitat de Barcelona, Barcelona, Spain.
authors.forename: Silvie
authors.initials: S
authors.lastname: Huijben
authors.affiliation: General Medicine Division, Massachusetts General Hospital, Boston, MA, USA.
authors.forename: Joshua
authors.initials: J
authors.lastname: Metlay
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Nicole
authors.initials: N
authors.lastname: Mideo
authors.affiliation: Centre for Infectious Disease Dynamics, The Pennsylvania State University, University Park, State College, PA, USA Departments of Biology and Entomology, The Pennsylvania State University, University Park, State College, PA, USA Centre for Immunology, Infection and Evolution, University of Edinburgh, Edinburgh, UK.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Pollitt
authors.affiliation: Centre for Infectious Disease Dynamics, The Pennsylvania State University, University Park, State College, PA, USA Departments of Biology and Entomology, The Pennsylvania State University, University Park, State College, PA, USA Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Read
authors.affiliation: Department of Zoology, Oxford University, Oxford, UK.
authors.forename: David L
authors.initials: DL
authors.lastname: Smith
authors.affiliation: Department of Health Policy, George Washington University, Washington, DC, USA.
authors.forename: Claire
authors.initials: C
authors.lastname: Standley
authors.affiliation: Centre for Infectious Disease Dynamics, The Pennsylvania State University, University Park, State College, PA, USA Departments of Biology and Entomology, The Pennsylvania State University, University Park, State College, PA, USA.
authors.forename: Nina
authors.initials: N
authors.lastname: Wale
authors.affiliation: Department of Ecology and Evolutionary Biology, Princeton University, Princeton, NJ, USA Fogarty International Center, National Institutes of Health, Bethesda, MD, USA.
authors.forename: Bryan
authors.initials: B
authors.lastname: Grenfell
mesh_terms: D000890:Anti-Infective Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D005075:Biological Evolution; D004352:Drug Resistance, Microbial / Q000235:genetics*; D006801:Humans; D007239:Infections / Q000188:drug therapy*; D064307:Microbiota / Q000187:drug effects / Q000235:genetics
chemical_list: D000890:Anti-Infective Agents
keywords: drug resistance; evolution; treatment strategies