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PPIs and H₂-Blockers Augment Risk for C. Difficile–Associated Disease

The biologic explanation for this association is not clear yet.

Clostridium difficile–associated disease (CDAD) is becoming more common and more severe, both in hospitals and in the community (Journal Watch Dec 20 2005). To determine whether rising rates of gastric-acid–suppressive therapy in the community might be partially responsible, researchers used a database of primary care patients in Great Britain. The database included 1672 patients who were diagnosed with CDAD from 1994 through 2004.

During the study period, the annual rate of disease rose more than 20-fold, use of proton-pump inhibitors (PPIs) increased, and antibiotic use actually decreased slightly. In a case-control analysis, older age, prior hospitalization, and antibiotic use all correlated strongly with increased risk for CDAD. Among the 1233 patients who had not been hospitalized in the year preceding their diagnoses, another case-control analysis confirmed that use of PPIs and use of H₂-blockers were both significant independent predictors of CDAD, a pattern that held even in patients without prior gastrointestinal disease. Use of nonsteroidal anti-inflammatory drugs was also an independent predictor of CDAD.

Comment: Gastric-acid suppression has been associated with an increased risk for bacterial enteric infections such as salmonellosis, and several studies now suggest that it also heightens risk for CDAD. The biologic explanation for this association is not immediately clear, as the spore forms of C. difficile that are thought to transmit disease are acid-resistant, but other drug effects might be responsible. The association with NSAID use, if confirmed, also awaits explanation. Clearly, we have not yet even begun to understand the full biologic and behavioral story of CDAD, especially in the community.

— Abigail Zuger, MD

Published in Journal Watch General Medicine January 10, 2006

Citation(s):

Dial S et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile–associated disease. JAMA 2005 Dec 21; 294:2989-95.

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