Handling Time-dependent Variables: Antibiotics and Antibiotic Resistance

L. Silvia Munoz-Price, Jos F. Frencken, Sergey Tarima, Marc Bonten

Research output: Contribution to journalArticlepeer-review

22 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)1558-1563
Number of pages6
JournalClinical Infectious Diseases
Issue number12
StatePublished - Jun 15 2016


  • Cox proportional hazards
  • antibiotics
  • hazard ratio
  • time-dependent variables

ASJC Scopus subject areas

  • Microbiology (medical)
  • Infectious Diseases


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