Clostridium difficile-associated disease in a setting of endemicity:: Identification of novel risk factors

Background. Previous studies of risk factors for Clostridium difficile-associated disease (CDAD) have been limited by small sample sizes and case-control study designs. Many of these studies were performed during outbreaks of CDAD. Colonization pressure and use of fluoroquinolones, vancomycin, and gastric acid suppressors have not been fully evaluated as risk factors for CDAD. The purpose of this study was to determine risk factors for endemic CDAD, including CDAD pressure, a modified version of colonization pressure. Methods. We performed a retrospective cohort study of 36,086 patients admitted to Barnes-Jewish Hospital (St. Louis, MO) during the period from 1 January 2003 through 31 December 2003. Administrative, laboratory, and pharmacy data were collected from electronic hospital databases. Colonization pressure was measured through a surrogate variable (i.e., CDAD pressure). Multivariable pooled logistic regression models were used to evaluate independent risk factors for CDAD. Results. The analysis included 382 CDAD case patient admissions and 35,704 non-case patient admissions. Significant independent risk factors for CDAD included increasing age, admission(s) in the previous 60 days, hypoalbuminemia, leukemia and/or lymphoma, mechanical ventilation, and receipt of antimotility drugs, histamine-2 blockers, proton pump inhibitors, intravenous vancomycin, fluoroquinolones, and first-, third-, or fourth-generation cephalosporins. Increasing CDAD pressure was a strong risk factor for CDAD (for a CDAD pressure > 1.4, the odds ratio was 4.0; 95% confidence interval, 2.9-5.6). Receipt of metronidazole was protective against CDAD (odds ratio, 0.5; 95% confidence interval, 0.3-0.6). Conclusions. This study identified the previously underrecognized CDAD risk factors of CDAD pressure and vancomycin. More studies are needed to evaluate the relationship between CDAD, these risk factors, and use of gastric acid suppressors and fluoroquinolones.