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Colon/small Bowel

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

The American Journal of Gastroenterology volume 103, pages 23082313 (2008) | Download Citation




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.


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 H2-blockers, renal failure, diabetes mellitus, immunosuppression, malignancy, and gastrointestinal disease.


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 [CI]= 1.7–8.3; P < 0.001), and with renal failure (OR = 5.7, CI = 1.3–39.1; P = 0.02).


This study showed elevated risk of developing CDAD in hospitalized patients with acid suppressive therapy, especially when PPIs were used.

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This study was supported by a research grant provided by Wichita Medical Research and Educational Foundation (WMREF) for statistical consultation that was performed by University of Kansas School of Medicine. The authors of this study would like to acknowledge Jim Rosendale, data architect for Wesley Medical Center's computer system, for his assistance with data reporting and Dr. Maha Assi, Infection Disease Consultant, for her help and support.

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  1. Wesley Medical Center, Wichita, Kansas

    • Mohammed Aseeri
    • , Todd Schroeder
    • , Joan Kramer
    •  & Rosalee Zackula


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Correspondence to Mohammed Aseeri.



Table 1: Subjects with C. difficile Toxin Positive Who Were Excluded From the Study

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