This article examines the relationship between acid-suppressive therapy and Clostridium difficile infection. C difficile infection is increasingly common in the United States, with annual medical costs over $1 billion, and is primarily spread as a hospital-acquired infection. It has been speculated that acid-suppressive therapy such as proton pump inhibitors and histamine-receptor antagonists may lead to increased rates of C difficile infection, but this theory has not been confirmed by prior research.

The authors performed a pharmacoepidemiologic cohort study that analyzed data from 101,796 patients discharged between 2004 and 2008 from a large, urban, tertiary care center. Of these patients, 665 (0.7%) had a C difficile infection.

Key Findings:

• Increasing levels of pharmacologic acid suppression are independently associated with increased rates of nosocomial C difficile infection.
• Patients receiving proton pump inhibitors multiple times a day were 2.36 times more likely to develop a C difficile infection than patients not receiving any acid suppressive therapy after adjusting for other variables. Similarly, patients receiving proton pump inhibitor therapy once a day were 1.74 times more likely to develop an infection than patients not receiving any acid suppressive therapy.
• Patients receiving histamine-receptor antagonist therapy were 1.53 times more likely to develop a C difficile infection than patients not receiving acid suppressive therapy.

While this study cannot prove that increasing acid-suppressive therapy causes increased levels of hospital-acquired C difficile infection, it provides strong evidence in favor of this theory.