Impact of Severity of Illness Bias and Control Group Misclassification Bias in Case-Control Studies of Antimicrobial-Resistant Organisms

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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.Patients: : 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]).Conclusion: : Requiring control-patients to have at least one clinical culture introduces a selection bias likely because it eliminates patients with less severe illness.