Impact of Acid Suppressants on the Development of Clostridioides difficile Infection and Possible Preventive Effects of Probiotic Formulations

Chihiro Shiraishi,1 Hideo Kato,2,3 Takuya Iwamoto2,3 1Department of Emergency and Disaster Medical Pharmacy, Faculty of Pharmaceutical Sciences, Fukuoka University, Fukuoka, Japan; 2Department of Pharmacy, Mie University Hospital, Mie, Japan; 3Department of Clinical Pharmaceutics, Division of Clinical Medical Science, Mie University Graduate School of Medicine, Mie, JapanCorrespondence: Hideo Kato, Department of Pharmacy, Mie University Hospital, 2-174, Edobashi, Tsu, Mie, 514-8507, Japan, Tel +81-59-232-1111, Email [email protected]: The comparative effectiveness and potential impact of individual proton pump inhibitors (PPIs) on the development of Clostridioides difficile infection (CDI) remain unclear. Additionally, there is insufficient evidence to support the use of probiotics for CDI prevention outside clinical trials. This study aimed to identify the PPIs that are most associated with CDI development and to determine whether probiotic co-administration can reduce this risk.Methods: We retrospectively analyzed the data of 3287 patients tested for CDI at Mie University Hospital between January 2014 and June 2024, excluding 1917 patients who had received antibiotics within the prior 3 months. The PPIs studied included esomeprazole, omeprazole, rabeprazole, and lansoprazole.Results: Univariate logistic regression analysis revealed age and esomeprazole use as potential risk factors for CDI (p = 0.009). Although not significant, the co-administration of probiotics tended to reduce the incidence of CDI in patients receiving esomeprazole (3.8% vs 10.4%, p = 0.060). Patients prescribed vonoprazan had a significantly higher rate of concomitant probiotic use than did those prescribed esomeprazole (p =  0.025).Conclusion: Our findings suggest that esomeprazole use and advanced age may increase the risk of CDI. Additionally, probiotics may help prevent CDI during PPI therapy. Selecting PPIs based on individual bleeding profiles and considering probiotics could be beneficial to mitigate the risk of CDI.Plain Language Summary: Esomeprazole use and advanced age may increase the risk of Clostridioides difficile infection (CDI). Probiotics may help prevent CDI during PPI therapy. Therefore, selecting PPIs based on bleeding risk and considering adjunctive probiotic may be beneficial in mitigating CDI incidence. Keywords: proton pump inhibitors, Clostridioides difficile infection, probiotics