title: Handling Time-dependent Variables: Antibiotics and Antibiotic Resistance.
abstract: Elucidating quantitative associations between antibiotic exposure and antibiotic resistance development is important. In the absence of randomized trials, observational studies are the next best alternative to derive such estimates. Yet, as antibiotics are prescribed for varying time periods, antibiotics constitute time-dependent exposures. Cox regression models are suited for determining such associations. After explaining the concepts of hazard, hazard ratio, and proportional hazards, the effects of treating antibiotic exposure as fixed or time-dependent variables are illustrated and discussed. Wider acceptance of these techniques will improve quantification of the effects of antibiotics on antibiotic resistance development and provide better evidence for guideline recommendations.
authors.affiliation: Institute for Health and Society.|Department of Medicine, Medical College of Wisconsin, Milwaukee.
authors.forename: L Silvia
authors.initials: LS
authors.lastname: Munoz-Price
authors.affiliation: Julius Center for Health Sciences and Primary Care.|Department of Intensive Care Medicine.
authors.forename: Jos F
authors.initials: JF
authors.lastname: Frencken
authors.affiliation: Institutefor Health and Society.
authors.forename: Sergey
authors.initials: S
authors.lastname: Tarima
authors.affiliation: Julius Center for Health Sciences and Primary Care.|Department of Medical Microbiology, University Medical Center Utrecht, The Netherlands.
authors.forename: Marc
authors.initials: M
authors.lastname: Bonten
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D001424:Bacterial Infections / Q000188:drug therapy / Q000453:epidemiology; D004352:Drug Resistance, Microbial; D015340:Epidemiologic Research Design; D006760:Hospitalization; D006761:Hospitals; D006801:Humans; D016016:Proportional Hazards Models; D013997:Time Factors
chemical_list: D000900:Anti-Bacterial Agents
keywords: Cox proportional hazards; antibiotics; hazard ratio; time-dependent variables