title: Origin and proliferation of multiple-drug resistance in bacterial pathogens.
abstract: Many studies report the high prevalence of multiply drug-resistant (MDR) strains. Because MDR infections are often significantly harder and more expensive to treat, they represent a growing public health threat. However, for different pathogens, different underlying mechanisms are traditionally used to explain these observations, and it is unclear whether each bacterial taxon has its own mechanism(s) for multidrug resistance or whether there are common mechanisms between distantly related pathogens. In this review, we provide a systematic overview of the causes of the excess of MDR infections and define testable predictions made by each hypothetical mechanism, including experimental, epidemiological, population genomic, and other tests of these hypotheses. Better understanding the cause(s) of the excess of MDR is the first step to rational design of more effective interventions to prevent the origin and/or proliferation of MDR.
authors: Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
authors: Hsiao-Han
authors: HH
authors: Chang
authors: Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Epidemiology of Microbial Diseases, Yale School of Public Health, New Haven, Connecticut, USA.
authors: Ted
authors: T
authors: Cohen
authors: Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Division of Infectious Diseases, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA.
authors: Yonatan H
authors: YH
authors: Grad
authors: Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA.
authors: William P
authors: WP
authors: Hanage
authors: The World Health Organization Collaborating Centre for Surveillance of Antimicrobial Resistance, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts, USA.
authors: Thomas F
authors: TF
authors: O'Brien
authors: Center for Communicable Disease Dynamics, Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA Department of Immunology and Infectious Diseases, Harvard School of Public Health, Boston, Massachusetts, USA mlipsitc@hsph.harvard.edu.
authors: Marc
authors: M
authors: Lipsitch
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001419:Bacteria / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D001424:Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology / Q000382:microbiology*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D054884:Host-Pathogen Interactions; D006801:Humans
chemical_list: D000900:Anti-Bacterial Agents
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