Journal of Gastroenterology

, Volume 54, Issue 12, pp 1052–1060 | Cite as

Effects of proton pump inhibitor use on risk of Clostridium difficile infection: a hospital cohort study

  • Yoon Hee Park
  • Jong Mi Seong
  • Soyeon Cho
  • Hye Won Han
  • Jae Youn Kim
  • Sook Hee An
  • Hye Sun GwakEmail author
Original Article—Alimentary Tract



Although there are several studies on the association between use of proton pump inhibitors (PPIs) and increased Clostridium difficile infection (CDI) risk, detailed studies analyzing the effects of PPI use on CDI risk are lacking. The present study investigated the association of the dose, duration, and types of PPIs with CDI risk.


A single-center, cohort study was conducted on patients admitted to a hospital. The exposed cohort comprised patients who were prescribed PPIs at least once during the study period, and a control cohort was prepared by randomly assigning an index date to patients who did not use PPIs ensuring the same distribution of index dates as in the exposed cohort and matching sex, age, hospitalization period, and date of admission.


PPI use increased the risk of CDI by 1.8-fold [95% confidence interval (CI) 1.5–2.2]. CDI risk increased by 1.8-fold with esomeprazole (95% CI 1.4–2.2) and 2.0-fold with pantoprazole (95% CI 1.5–2.8). Patients who used a high dose had a higher risk than those who used a medium dose [adjusted hazard ratio (HR) 2.0 vs 1.3]. The risk of CDI increased 4.2-fold when the PPI exposure period was 6 days or shorter than 6 days.


Our study showed that PPI use was associated with an increased risk of developing CDI and the risk of CDI was dose dependent. Therefore, PPIs should only be used at proper doses and only for the necessary indications to avoid CDI risk.


Proton pump inhibitor Clostridium difficile Diarrhea 


Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

535_2019_1598_MOESM1_ESM.docx (13 kb)
Supplementary file1 (DOCX 12 kb)


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Copyright information

© Japanese Society of Gastroenterology 2019

Authors and Affiliations

  1. 1.Division of Life and Pharmaceutical Sciences, College of PharmacyEwha Womans UniversitySeoulRepublic of Korea
  2. 2.Department of PharmacyAsan Medical CenterSeoulRepublic of Korea
  3. 3.College of PharmacyWonkwang UniversityIksanRepublic of Korea

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