Gastric Acid Suppression by Proton Pump Inhibitors as a Risk Factor for Clostridium difficile-Associated Diarrhea in Hospitalized Patients

BACKGROUND: Evidence for the association between Clostridium difficile (C. difficile) and the use of proton pump inhibitor (PPI) is unclear. This study investigated the relationship between Clostridium difficile-associated diarrhea (CDAD) and exposure to acid suppressive therapy in hospitalized adult patients while controlling for the most common predisposing risk factors. METHODS: A retrospective case-control study was conducted at a local hospital of all hospitalized patients between October 1, 2005 and September 30, 2006 who developed CDAD during hospitalization. Subjects were determined to have CDAD if there was a positive C. difficile toxin and clinical correlation of diarrhea at the time of diagnosis. Subjects were pair-matched to controls on the following factors: admission date, antibiotic exposure, gender, age groups, patient location (medical or surgical unit), and room type at time of admission. Seven risk factors were assessed for association with onset of CDAD: exposure to PPIs or H-2-blockers, renal failure, diabetes mellitus, immunosuppression, malignancy, and gastrointestinal disease. RESULTS: Ninety-four cases were successfully matched to controls. Cases were more likely than controls to receive acid suppressive therapy during hospitalization, 72 (76.6%) versus 40 (42.6%), respectively, P = 0.030. In a multivariate exact conditional logistic regression analysis, CDAD was associated with use of PPI (odds ratio [OR] = 3.6, 95% confidence interval [Cl] = 1.7-8.3; P < 0.001), and with renal failure (OR = 5.7, Cl = 1.3-39.1; P = 0.02). CONCLUSION: This study showed elevated risk of developing CDAD in hospitalized patients with acid suppressive therapy, especially when PPIs were used.