Proton pump inhibitors and risk of Clostridium difficile infection: a multi-country study using sequence symmetry analysis

Elizabeth E. Roughead, Esther W. Chan, Nam Kyong Choi, Jenna Griffiths, Xue Mei Jin, Joongyub Lee, Michio Kimura, Tomomi Kimura, Kiyoshi Kubota, Edward Chia Cheng Lai, Kenneth K.C. Man, Tuan Anh Nguyen, Nobuhiro Ooba, Byung Joo Park, Tsugumichi Sato, Ju Young Shin, Tong Tong Wang, Ian C.K. Wong, Yea Huei Kao Yang, Nicole L. Pratt

Research output: Contribution to journalArticlepeer-review

33 Scopus citations


Objective: To determine the association between incident proton pump inhibitor (PPI) use and Clostridium difficile infections across multiple countries Method: National data covering the total population in Australia and Korea, the Canadian population over 65 years and a 3 million person random sample data set from Taiwan were assessed, as were data from a worker insurance population and a hospital inpatient/outpatient population in Japan. Sequence symmetry analysis was used to assess the association with oral vancomycin dispensing as the outcome of interest. Results: 54,957 patients were included. Positive associations were observed in Australia; adjusted sequence ratio (ASR) 2.48 (95% CI 1.90, 3.12), Korea ASR 2.15 (95%CI 2.11, 2.19), Canada ASR 1.45 (95% CI 1.16, 1.79), Japan hospital dataset ASR 3.21 (95%CI 2.12, 4.55) and Japan worker insurance dataset ASR 5.40 (95% CI 2.73, 8.75). The pooled result was ASR 2.40 (95%CI 1.88, 3.05) and 3.16 (95%CI 1.95, 5.10) when limited to Japan, Korean and Taiwan. Results did not vary by individual PPI. The temporal analysis showed effects within the first two weeks of PPI initiation. Conclusion: Our study confirms the association between PPI initiation and C. difficile infections across countries in the Asia-Pacific region.

Original languageEnglish
Pages (from-to)1589-1595
Number of pages7
JournalExpert Opinion on Drug Safety
Issue number12
StatePublished - 1 Dec 2016

Bibliographical note

Publisher Copyright:
© 2016 Informa UK Limited, trading as Taylor & Francis Group.


  • Asia
  • Clostridium difficile
  • Proton pump inhibitors
  • adverse event
  • sequence symmetry analysis


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