JPERM

Objective: Acid-suppressive therapy is commonly used for stress ulcers; however, concerns have been raised regarding its potential to increase the risk of Clostridioides difficile infection (CDI). This study aimed to compare the risk of CDI associated with proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) among acid-suppressive agents. Methods: We conducted a meta-analysis to systematically evaluate the risk of CDI associated with PPIs compared to H2RAs. We searched 3 major databases up to April 30, 2024. The primary outcome was the incidence of CDI. Results: The meta-analysis of 14 articles involving 160,085 patients showed PPIs were associated with a 1.50-fold increase in the risk of CDI compared to H2RAs [95% CI: 1.22–1.85, I² = 39%]. In a subgroup analysis of 8 out of 14 studies, which included 88,393 critically ill patients, PPIs were linked to a 1.58-fold increase in the risk of CDI compared to H2RAs [95% CI: 1.10–2.27, I² = 61%]. In observational studies, PPIs were associated with a 1.55-fold increase in the risk of CDI [95% CI: 1.26–1.91, I² = 33%]. In randomized trials, PPIs were not significantly associated with an increased risk of CDI compared to H2RAs [OR 1.92, 95% CI: 0.51–7.25, I² = 41%]. Conclusion: Our findings indicate that PPIs are associated with a higher risk of CDI compared to H2RAs. Further well-controlled clinical trials are necessary to confirm these results.

KeywordsAcid-suppressive therapy, Proton Pump Inhibitors, Histamine H2 Antagonists, Clostridioides difficile