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Increased risk for diarrhea infection with use of gastric acid-suppressive agents

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.

Clostridium difficile infection, an important cause of nosocomial diarrhea, has also been reported to be an important cause of diarrhea in the community.

A British study, published in the JAMA, 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 C difficile–associated disease are increasing. While the rates of C difficile–associated disease in the community are much lower than in the hospital setting, the absolute number of cases in the community could be significant.

Sandra Dial, 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 C difficile–associated disease. 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 C difficile–associated disease; use of H2-receptor antagonists was associated with twice the rate of C difficile–associated disease. 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 C difficile–associated disease 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 C difficile–associated disease as an important public health concern. While the overall rate of C difficile–associated disease 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 C difficile–associated disease needs to be considered and more completely characterized," the authors conclude.

Source: American Medical Association, 2005


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