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

ABSTRACT

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.

KEYWORDS:

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

Acknowledgements

We thank the DUSC Secretariat, who extracted the PBS prescription data and processed it using SAS code supplied by the University of South Australia.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Additional information

Funding

This research was supported by an Australian Government National Health and Medical Research Council (NHMRC) GNT 1040938, N Pratt is supported by NHMRC GNT1035889. EE Roughead is supported by NHMRC GNT 1110139 NKC has received research funding from Korean National Research Foundation.