title: Impact of severity of illness bias and control group misclassification bias in case-control studies of antimicrobial-resistant organisms.
abstract: BACKGROUND
  Case-control studies often analyze risk factors for antibiotic resistance. Recently published articles have illustrated that randomly selected control-patients may be preferable to those with the susceptible phenotype of the organism. A possible methodologic problem with randomly selected control-patients is potential bias due to control group misclassification. This occurs if some control-patients did not have clinical cultures performed and thus might have been unidentified case-patients. If this bias exists, these studies might be expected to report lower odds ratios (ORs) because control-patients would be more like case-patients.
  
  
  OBJECTIVE
  To analyze potential biases that might arise due to control group misclassification and potentially larger selection biases that may be introduced if control-patients are required to have at least one clinical culture.
  
  
  METHODS
  One hundred twenty case-patients, 770 control-patients in group 1, and 510 control-patients in group 2.
  
  
  METHODS
  Two case-control studies. Case-patients had clinical cultures positive for imipenem-resistant Pseudomonas aeruginosa. The first group of control-patients were random. The second group of control-patients were identical to those in group 1 except being required to have at least one clinical culture.
  
  
  RESULTS
  Univariate analyses showed higher ORs for case-patients versus control-patients in group 1 (imipenem [OR, 12.5], piperacillin-tazobactam [OR, 3.7], and vancomycin [OR, 4.7]) as compared with case-patients versus control-patients in group 2 (imipenem [OR, 8.0], piperacillin-tazobactam [OR, 2.5], and vancomycin [OR, 3.0]).
  
  
  CONCLUSIONS
  Requiring control-patients to have at least one clinical culture introduces a selection bias likely because it eliminates patients with less severe illness.
authors.affiliation: Department of Epidemiology and Preventive Medicine, University of Maryland, College Park, USA. aharris@epi.umaryland.edu
authors.forename: Anthony D
authors.initials: AD
authors.lastname: Harris
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Carmeli
authors.forename: Matthew H
authors.initials: MH
authors.lastname: Samore
authors.forename: Keith S
authors.initials: KS
authors.lastname: Kaye
authors.forename: Eli
authors.initials: E
authors.lastname: Perencevich
mesh_terms: D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D004351:Drug Resistance; D006801:Humans; D015378:Imipenem / Q000627:therapeutic use*; D018579:Patient Selection; D011552:Pseudomonas Infections / Q000145:classification / Q000188:drug therapy*; D015983:Selection Bias; D012720:Severity of Illness Index
chemical_list: D000900:Anti-Bacterial Agents; D015378:Imipenem