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Background: Patients colonized or infected with vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus may be at risk of acquiring vancomycin-resistant S. aureus if the vanA gene is transferred from vancomycin-resistant enterococcus to methicillin-resistant S. aureus., Objective: Our goal was to identify risk factors for cocolonization or coinfection (CC/CI) with vancomycin-resistant enterococcus and methicillin-resistant S. aureus., Design: We conducted a descriptive, epidemiologic study of all patients with CC/CI identified from January 1998 to May 2003 and a nested case-control study of a cohort of patients hospitalized in the burn and wound unit., Setting: We conducted our study in a 813-bed tertiary care university teaching hospital., Population: The study population consisted of patients found to have CC/CI during the study period., Methods: Descriptive epidemiologic data were collected from hospital records of all patients identified as having CC/CI. A subset of patients hospitalized in the burn and wound unit were included in a case-control study., Results: CC/CI was detected in 71% of the patients during a single hospital stay. The burn and wound unit, which does active surveillance for both organisms, and the general medicine unit, which does not do active surveillance for either organism, cared for more than one-half of these patients. Among patients being cared for in the burn and wound unit, having exposure to 2 or more invasive devices (central venous catheters, indwelling urinary catheters, and enteral feeding tubes) and renal insufficiency were independent risk factors for CC/CI., Conclusions: Patients with CC/CI are the population at greatest risk for vancomycin-resistant S. aureus colonization or infection. The number of invasive devices to which patients are exposed and, thus, possibly the patients' underlying severity of illness, as well as renal insufficiency, appear to be risk factors for CC/CI.