Original Contribution | Published:

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

Subjects

Abstract

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 H2-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 [CI]= 1.7–8.3; P < 0.001), and with renal failure (OR = 5.7, CI = 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.

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References

  1. 1.

    , , . Clostridium difficile colitis. N Engl J Med 1994;330:257–262.

  2. 2.

    , . Epidemiology of Clostridium difficile-associated infection. Clin Microbiol infect 2001;7:405–441.

  3. 3.

    , . Update on Clostridium difficile. Curr Treat Options Gastroenterol 2006;9:265–271.

  4. 4.

    , , , et al. Length of stay, and proton pump inhibitors: Key factors in Clostridium difficile-associated disease in nursing home patients. J Am Med Dir Assoc 2005;6:105–108.

  5. 5.

    . Clinical impact and associated costs of Clostridium difficle-associated disease. J Antimicrob Chemother 1998;41(Suppl):C5–C12.

  6. 6.

    . Clostridium difficile-associated diarrhea. Am Fam Physician 2005;71:921–928.

  7. 7.

    , , , et al. Health care costs and mortality associated with nosocomial diarrhea due to Clostridium difficile. Clin Infect Dis 2002;34:346–353.

  8. 8.

    , , , et al. Clostridium difficile-associated diarrhoea in hospitalised patients. J Clin Pharm Ther 2000;25:101–109.

  9. 9.

    , , , et al. Emergence of fluoroquinolones as the predominant risk factor for Clostridium difficile-associated diarrhea: A cohort study during an epidemic in Quebec. Clin Infect Dis 2005;41:1254–1260.

  10. 10.

    , , . Antibiotics and hospital-acquired Clostridium difficle-associated diarrhea: A systemic review. J Antimicrob Chemother 2003;51:1339–1350.

  11. 11.

    , , , et al. Frequency of antibiotic-associated diarrhoea in 2462 antibiotic-treated hospitalized patients: A prospective study. J Antimicrob Chemother 2001;47:43–50.

  12. 12.

    . Risk for Clostridium difficile infection. J Hosp Infect 1998;40:1–15.

  13. 13.

    , , , et al. Third generation cephalosporins as a risk factor for Clostridium difficile-associated disease: A four-year survey in a general hospital. J Antimicrob Chemother 1989;23:623–631.

  14. 14.

    , , , et al. Antibiotics and Clostridium difficile diarrhea in the ambulatory care setting. Clin Ther 2000;22:91–102.

  15. 15.

    , , , et al. Nosocomial Clostridium colonization and disease. Lancet 1990;336:97–100.

  16. 16.

    , , , et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA 2005;21:2989–2995.

  17. 17.

    , , , et al. Proton pump inhibitor therapy is a risk factor for Clostridium difficile-associated diarrhoea. Aliment Pharmacol Ther 2006;24:613–619.

  18. 18.

    , , , et al. Proton pump inhibitors as a risk factor for Clostridium difficile diarrhea. J Hosp Infect 2003;54:243–245.

  19. 19.

    , , , et al. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: Cohort and case-control studies. CMAJ 2004;171:33–38.

  20. 20.

    CAG News. Clostridium difficile-associated diarrhea (CDAD) and proton pump inhibitor therapy: CAG Position Statement. Can J Gastroenterol 2005;19:1–3.

  21. 21.

    , , , et al. Clostridium difficile colitis associated with treatment of Helicobacter pylori infection. Am J Gastroenterol 1998;93:1175–1176.

  22. 22.

    , , , et al. Gastric acid suppression does not promote clostridial diarrhoea in the elderly. QJM 2000;93:175–181.

  23. 23.

    , , , et al. Proton pump inhibitors and hospitalization for Clostridium difficile-associated disease: A population-based study. Clin Infect Dis 2006;15:1272–1276.

  24. 24.

    , , , et al. Proton pump inhibitor use and risk of community-acquired Clostridium difficile-associated disease defined by prescription for oral vancomycin therapy. CMAJ 2006;175:745–748.

  25. 25.

    , , . Population dynamics of ingested Clostridium difficile in the gastrointestinal tract of the Syrian hampster. J Infect Dis 1985;151:355–361.

  26. 26.

    , , , et al. Hospital use of acid-suppressive medications and its fall-out on prescribing in general practice: A 1-month survey. Aliment Pharmacol Ther 2003;17:1503–1506.

  27. 27.

    , , . Prescriptions for antiulcer drugs in Australia: volume, trends, and costs. BMJ 2001;323:1338–1339.

  28. 28.

    , , , et al. Acquisition of Clostridium difficile from the hospital environment. Am J Epidemiol 1988;127:1289–1294.

  29. 29.

    , , . Prospective study of Clostridium difficile intestinal colonization and disease following single-dose antibiotic prophylaxis in surgery. Antimicrob Agents Chemother 1991;35:208–210.

  30. 30.

    K/DOQI. Clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. National Guideline Clearinghouse. Available at: . Accessed on September 24, 2006.

  31. 31.

    . Power calculation for matched case-control studies. Biometrics 1998;44:1157–1168.

  32. 32.

    (n.d.). Log-Linear, logit, and probit models: Conditional logit models, from statnotes: Topics in multivariate analysis. Available at: . Accessed on March 26, 2007.

  33. 33.

    , , , et al. Problem due to small samples and spares data in conditional logistic regression analysis. Am J Epidemiol 2000;151:531–539.

  34. 34.

    Cytel Statistical Software & Services. LogXact 7 with cytel studio: Discrete regression software featuring exact methods, user manual. Cambridge, MA 2005:223.

  35. 35.

    , , , et al. Acid suppressive therapy use on an inpatient internal medicine service. Ann Pharmacother 2006;40:1261–1266.

  36. 36.

    , , . Overuse of acid-suppressive therapy in hospitalized patients. Am J Gastroenterol 2000;95:3118–3122.

  37. 37.

    , . Stress ulcer prophylaxis in hospitalized patients not in intensive care units. Am J Health Syst Pharm 2007;64:1396–1400.

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Acknowledgements

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.

Author information

Affiliations

  1. Wesley Medical Center, Wichita, Kansas

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

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Corresponding author

Correspondence to Mohammed Aseeri.

Appendices

APPENDIX: DEFINITION OF OUTCOME MEASURES

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

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DOI

https://doi.org/10.1111/j.1572-0241.2008.01975.x

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