Use of gastric acid-suppressive agents linked with increased risk for diarrhea infection

December 19, 2005

Use of gastric acid-suppressive therapy, particularly proton pump inhibitors, is associated with an increased risk for an infection that is a significant cause of diarrhea, according to a study in the December 21 issue of JAMA.

Clostridium difficile infection, an important cause of nosocomial (taking place or originating in a hospital) diarrhea, has also been reported to be an important cause of diarrhea in the community, according to background information in the article. A British study identified C difficile as the third most common cause of infectious diarrhea in patients aged 75 years and older seen by general practitioners. A French study performed in outpatients to whom antibiotics were prescribed reported an incidence of C difficile-associated disease (CDAD) of 1.5 percent and estimated that up to 920,000 outpatients nationwide could potentially develop toxinogenic CDAD yearly. Recent data suggest that both the rates and severity of nosocomial CDAD are increasing. While the rates of CDAD in the community are much lower than in the hospital setting, the absolute number of cases in the community could be significant.

Sandra Dial, M.D., M.Sc., and colleagues from McGill University, Montreal, conducted a study to determine whether the use of gastric acid-suppressant drugs is associated with the risk of community-acquired CDAD. This study consisted of two population-based case-control studies using the United Kingdom General Practice Research Database (GPRD). In the first study, the researchers identified all 1,672 cases of C difficile recorded between 1994 and 2004 among all patients registered for at least 2 years in each practice.

The researchers found that of these 1,672 patients, 1,233 (74 percent) had not been hospitalized in the year prior to diagnosis and were considered community-acquired. There has been a significant increase in the rate of C difficile cases diagnosed in the community from less than 1 per 100,000 persons in 1994 to 22 per 100,000 in 2004. During this period, the rate of prescriptions of antibiotics has decreased and that of proton pump inhibitors has increased. After controlling for certain variables, current use of proton pump inhibitors was associated with nearly 3 times the rate of CDAD; use of H2-receptor antagonists was associated with twice the rate of CDAD. Current use of NSAIDs but not aspirin was associated with a 30 percent increased rate of C difficile.

"Clostridium difficile-associated disease is becoming an important public health issue. Significant increases in number of cases of CDAD in Great Britain since the 1990s have been observed, including the exponential increase in the community observed in this study. Genetic mutations that may be associated with increased transmissibility and increased severity are also being reported. These factors combined with reports of outbreaks in the United States and the recent outbreak in the Canadian province of Quebec justify considering CDAD as an important public health concern. While the overall rate of CDAD in the GPRD is much lower than in the hospital setting, it appears to be increasing significantly even in the face of both our data and another report to suggest that outpatient antibiotic prescribing in the GPRD is decreasing. Acid-suppressive agents are among the most frequently prescribed medications in the United Kingdom and North America, and it is in this context that the contribution of these agents by potentially increasing the pool of susceptible hosts to the increasing rates of CDAD needs to be considered and more completely characterized," the authors conclude.
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(JAMA.2005; 294:2989-2995. Available pre-embargo to the media at www.jamamedia.org)

Editor's Note: This study was funded by the Canadian Institutes of Health Research (CIHR) and the Canadian Foundation for Innovation (CFI). Dr. Dial is a Chercheur-Boursier Clinicien and co-author Dr. Barkun a Chercheur National awardee, both from the Fonds de la recherche en santé du Québec (FRSQ). Co-author Dr. Suissa is the recipient of a Distinguished Investigator award from CIHR. Dr. Barkun is a consultant for AstraZeneca Inc. and Altana Pharma Inc. No other authors reported financial disclosures.

The JAMA Network Journals

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