S2138 Proton Pump Inhibitor Use and Risk of Clostridioides difficile Infection in Patients With Inflammatory Bowel Disease: A Propensity Score–Matched Cohort Study

Introduction: Proton pump inhibitors (PPIs) are commonly prescribed in patients with inflammatory bowel disease (IBD). However, their impact on the risk of Clostridioides difficile infection (CDI) remains unclear. We aimed to investigate whether PPI use increases the risk of CDI among patients with IBD. Methods: Using the TriNetX Global Collaborative Network, we identified adult patients (≥16 years) with IBD (Crohn’s disease or ulcerative colitis). Two cohorts were defined: (1) IBD patients exposed to PPIs, and (2) IBD patients not exposed to PPIs or systemic corticosteroids (including prednisone). Patients with prior CDI were excluded. A 1:1 propensity score–matched analysis (n = 167,233 per group) was performed based on demographics and medication use. Outcomes included risk, time-to-event, and frequency of CDI over a 3-year follow-up. Results: After matching, PPI use was associated with a significantly higher risk of CDI (6.0% vs 2.4%; risk ratio: 2.475, 95% confidence interval [CI]: 2.386–2.567; P < 0.001). Kaplan-Meier analysis confirmed reduced CDI-free survival in the PPI group (hazard ratio: 2.346, 95% CI: 2.260–2.435; P < 0.001). The mean number of CDI episodes was also higher among PPI users (mean: 1.72 vs 1.26; P < 0.001). Conclusion: Among patients with IBD, PPI use is associated with a significantly increased risk of developing CDI. Clinicians should consider alternative acid suppression strategies and assess PPI necessity in this population.