title: Examining the relationship between multidrug-resistant organism acquisition and exposure to antimicrobials in long-term care populations: a review.
abstract: Methodological approaches to examine the association between antimicrobial exposure and multidrug-resistant organism (MDRO) acquisition are complex. This report's objectives are to review approaches used in and findings of prior studies in the long-term care setting, illustrate how these challenges were addressed in a recently completed large prospective study, and discuss strategies for future studies.
  
  
  
  Key design and analytic approaches used in studies conducted since 2000 examining the association between antimicrobial exposure and MDRO acquisition in the long-term care setting were reviewed. The Study of Pathogen Resistance and Exposure to Antimicrobials in Dementia (SPREAD) in nursing home residents in Boston from 2009 to 2014 is used to illustrate how to approach these challenges.
  
  
  
  Prior investigations reporting the association between antimicrobial exposure and MDRO acquisition vary considerably in their approaches. In SPREAD, grouped-time hazard models with complementary log-log link function were used to model acquisition accounting for clustering within facilities using generalized estimating equations and including all days of exposure before acquisition.
  
  
  
  Future studies in these populations should make use of all available acquisition status data, incorporate the timing of antimicrobial exposure relative to acquisition, and collect detailed covariate information that facilitates examining confounding by indication.
authors.affiliation: Department of Pediatrics, University of Washington, Seattle; Center for Clinical and Translational Research, Seattle Children's Research Institute, Seattle, WA. Electronic address: mshaff@uw.edu.
authors.forename: Michele L
authors.initials: ML
authors.lastname: Shaffer
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA.
authors.forename: Erika M C
authors.initials: EM
authors.lastname: D'Agata
authors.affiliation: Hebrew SeniorLife Institute for Aging Research, Boston, MA.
authors.forename: Daniel
authors.initials: D
authors.lastname: Habtemariam
authors.affiliation: Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA; Hebrew SeniorLife Institute for Aging Research, Boston, MA.
authors.forename: Susan L
authors.initials: SL
authors.lastname: Mitchell
mesh_terms: D000368:Aged; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001424:Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology; D001900:Boston; D024901:Drug Resistance, Multiple, Bacterial; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006094:Gram-Positive Bacteria / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D008134:Long-Term Care; D008297:Male; D008826:Microbial Sensitivity Tests; D016016:Proportional Hazards Models; D012866:Skilled Nursing Facilities
chemical_list: D000900:Anti-Bacterial Agents
keywords: Antimicrobial drug resistance; Antimicrobial exposure; Hazard models; Long-term care