Risk of Developing Clostridioides Difficile Infection with the Use of Proton Pump Inhibitors in Patients with Inflammatory Bowel Disease

Introduction: Patients with inflammatory bowel disease (IBD) have an increased risk of Clostridioides difficile infection (CDI). While antibiotic exposure has been considered the most prominent risk factor for CDI, proton pump inhibitor (PPI) use is another potential risk factor. Methods: From January 2017 to April 2021, we examined the University of Missouri’s IBD patients’ medical records. Laboratory-confirmed CDI diagnosis was the main outcome of interest. The usage of PPIs was the exposure of interest. The odds ratio between CDI risk in PPI users and non-users was estimated using logistic regression models. We investigated CDI risk with PPI use duration using stratified analysis. Results: Overall prevalence of CDI was 9%. 358 patients (42%) reported using PPI, with an average duration of ~30 months, with a range of 0.1 to 255. PPI use was associated with a higher risk of CDI in both the unadjusted (OR = 1.58 [0.98–2.53]; p = 0.06) and adjusted models (9.23 [2.11–40.34]; p = 0.003). Only those who used PPIs for less than 30 months had a greater risk of CDI in the stratified analysis (OR = 2.10 [1.16–3.38], p = 0.014). Long-term use (≥30 months) did not increase the incidence of CDI (OR = 0.74 [0.29, 1.83]; p = 0.510). Discussion: This is the single largest study of the US general IBD population to evaluate the association between PPI use and risk of developing CDI. PPI therapy was linked to a significant elevation in CDI risk, restricted to PPI use for up to 30 months. Histamine-2 receptor antagonists (H2RAs) did not increase the risk of CDI.