Clostridioides difficile infection in Patients Undergoing Acid-Suppressive Treatment: A Large Cohort Study with Propensity Score Matching

INTRODUCTION: Clostridioides difficile infection (CDI) is a significant concern in patients undergoing acid-suppressive therapy. This study aimed to evaluate and compare the risk of CDI in patients being treated with proton pump inhibitors (PPIs), histamine 2 receptor antagonists (H2RAs), or potassium-competitive acid blockers (PCAB; tegoprazan). METHODS: This retrospective observational cohort study evaluated 606,460 individuals prescribed PPIs, H2RAs, or tegoprazan for more than seven days, resulting in 22,431 matched individuals after propensity score matching. Primary outcome was CDI incidence within 12 weeks of medication use. RESULTS: Patients receiving PPIs exhibited a significantly higher relative risk (RR) (RR, 1.86; 95% confidence interval [CI]: 1.18–2.91) of developing CDI than those receiving H2RAs. Tegoprazan showed no significant increase in CDI risk (RR, 1.07; 95% CI: 0.64–1.79) compared to H2RAs. The risk of CDI increased with a longer duration of acid suppressant use. No dose-dependent differences in CDI occurrence were observed across PPI doses, and no significant differences were found in the incidence of severe CDI among the groups. CONCLUSIONS: Proton pump inhibitors were associated with a higher risk of CDI than H2RAs. These findings highlight the need for careful selection of acid-suppressive therapies, particularly in high-risk populations.