title: The case-case-control study design: addressing the limitations of risk factor studies for antimicrobial resistance.
abstract: OBJECTIVE
  There are significant limitations of the standard case-control study design for identifying risk factors for resistant organisms. The objective of this study was to develop a study design to overcome these limitations.
  
  
  METHODS
  Theoretical analysis of different types of study designs that can be used in risk factor studies for resistant organisms.
  
  
  RESULTS
  We developed the case-case-control study design, which uses two separate case-control analyses within a single study. The first analysis compares patients infected with resistant bacteria (resistant cases) with control-patients without infection caused by the target organism, who are therefore representative of the source population; and the second analysis compares patients infected with the susceptible phenotype of the target organism (susceptible cases) with the same control-patients without infection caused by the target organism. These two analyses provide risk models for (1) isolation of the resistant phenotype of the target organism as compared with the source population and (2) isolation of the susceptible phenotype of the organism as compared with the source population. When these two risk models are compared and contrasted, risk factors specifically associated with isolation of the resistant phenotype can be identified.
  
  
  CONCLUSIONS
  The case-case-control study design is an effective method for identifying risk factors for antimicrobial-resistant pathogens. Although the case-case-control study design has limitations, it is, in our opinion, more informative and less flawed than the standard case-control study design.
authors.affiliation: Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. kaye0001@mc.duke.edu
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Harris
authors.forename: Matthew
authors.initials: M
authors.lastname: Samore
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology; D016022:Case-Control Studies; D004351:Drug Resistance; D004926:Escherichia coli / Q000187:drug effects / Q000302:isolation & purification; D006801:Humans; D017053:Infection Control / Q000379:methods*; D012107:Research Design; D012307:Risk Factors
chemical_list: D000900:Anti-Bacterial Agents