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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
  • 476 Downloads

Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

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.

Keywords

Proton pump inhibitor Clostridium difficile Diarrhea 

Notes

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)

References

  1. 1.
    Lodato F, Poluzzi E, Raschi E, et al. Appropriateness of proton pump inhibitor (PPI) prescription in patients admitted to hospital: attitudes of general practitioners and hospital physicians in Italy. Eur J Intern Med. 2016;30:31–6.CrossRefGoogle Scholar
  2. 2.
    Zink DA, Pohlman M, Barnes M, et al. Long-term use of acid suppression started inappropriately during hospitalization. Aliment Pharmacol Ther. 2005;21:1203–9.CrossRefGoogle Scholar
  3. 3.
    Reid M, Keniston A, Heller JC, et al. Inappropriate prescribing of proton pump inhibitors in hospitalized patients. J Hosp Med. 2012;7:421–5.CrossRefGoogle Scholar
  4. 4.
    Schoenfeld AJ, Grady D. Adverse effects associated with proton pump inhibitors. JAMA Intern Med. 2016;176:172–4.CrossRefGoogle Scholar
  5. 5.
    Cheungpasitporn W, Thongprayoon C, Kittanamongkolchai W, et al. Proton pump inhibitors linked to hypomagnesemia: a systematic review and meta-analysis of observational studies. Ren Fail. 2015;37:1237–41.CrossRefGoogle Scholar
  6. 6.
    Kwok CS, Arthur AK, Anibueze CI, et al. Risk of Clostridium difficile infection with acid suppressing drugs and antibiotics: meta-analysis. Am J Gastroenterol. 2012;107:1011–9.CrossRefGoogle Scholar
  7. 7.
    Eom CS, Jeon CY, Lim JW, et al. Use of acid-suppressive drugs and risk of pneumonia: a systematic review and meta-analysis. CMAJ. 2011;183:310–9.CrossRefGoogle Scholar
  8. 8.
    Depestel DD, Aronoff DM. Epidemiology of Clostridium difficile infection. J Pharm Pract. 2013;26:464–75.CrossRefGoogle Scholar
  9. 9.
    Leffler DA, Lamont JT. Clostridium difficile infection. N Engl J Med. 2015;372:1539–48.CrossRefGoogle Scholar
  10. 10.
    Nehra AK, Alexander JA, Loftus CG, et al. Proton pump inhibitors: review of emerging concerns. Mayo Clin Proc. 2018;93:240–6.CrossRefGoogle Scholar
  11. 11.
    Dubberke ER, Olsen MA, Stwalley D, et al. Identification of medicare recipients at highest risk for Clostridium difficile infection in the US by population attributable risk analysis. PLoS ONE. 2016;11:e0146822.CrossRefGoogle Scholar
  12. 12.
    Loo VG, Bourgault AM, Poirier L, et al. Host and pathogen factors for Clostridium difficile infection and colonization. N Engl J Med. 2011;365:1693–703.CrossRefGoogle Scholar
  13. 13.
    Wei L, Ratnayake L, Phillips G, et al. Acid-suppression medications and bacterial gastroenteritis: a population-based cohort study. Br J Clin Pharmacol. 2017;83:1298–308.CrossRefGoogle Scholar
  14. 14.
    Garcia Rodriguez LA, Ruigomez A, Panes J. Use of acid-suppressing drugs and the risk of bacterial gastroenteritis. Clin Gastroenterol Hepatol. 2007;5:1418–23.CrossRefGoogle Scholar
  15. 15.
    Dial S, Alrasadi K, Manoukian C, et al. Risk of Clostridium difficile diarrhea among hospital inpatients prescribed proton pump inhibitors: cohort and case-control studies. CMAJ. 2004;171:33–8.CrossRefGoogle Scholar
  16. 16.
    Trifan A, Stanciu C, Girleanu I, et al. Proton pump inhibitors therapy and risk of Clostridium difficile infection: systematic review and meta-analysis. World J Gastroenterol. 2017;23:6500–15.CrossRefGoogle Scholar
  17. 17.
    Oshima T, Wu L, Li M, et al. Magnitude and direction of the association between Clostridium difficile infection and proton pump inhibitors in adults and pediatric patients: a systematic review and meta-analysis. J Gastroenterol. 2018;53:84–94.CrossRefGoogle Scholar
  18. 18.
    Tariq R, Singh S, Gupta A, et al. Association of gastric acid suppression with recurrent Clostridium difficile infection: a systematic review and meta-analysis. JAMA Intern Med. 2017;177:784–91.CrossRefGoogle Scholar
  19. 19.
    FDA Drug Safety Communication. Clostridium difficile associated diarrhea can be associated with stomach acid drugs known as proton pump inhibitors (PPIs). https://www.fda.gov/Drugs/DrugSafety/ucm290510.htm. Accessed 30 Dec 2018.
  20. 20.
    Lisi D. Pharmacotherapy self-assessment program 2018 BOOK1 infectious diseases. Lenexa: American College of Clinical Pharmacy; 2018.Google Scholar
  21. 21.
    Pai VG, Pai NV, Thacker HP, et al. Comparative clinical trial of S-pantoprazole versus racemic pantoprazole in the treatment of gastro-esophageal reflux disease. World J Gastroenterol. 2006;12:6017–20.CrossRefGoogle Scholar
  22. 22.
  23. 23.
    Wang L, Zhou L, Lin S, et al. A new PPI, ilaprazole compared with omeprazole in the treatment of duodenal ulcer: a randomized double-blind multicenter trial. J Clin Gastroenterol. 2011;45:322–9.CrossRefGoogle Scholar
  24. 24.
  25. 25.
    Dalton BR, Lye-Maccannell T, Henderson EA, et al. Proton pump inhibitors increase significantly the risk of Clostridium difficile infection in a low-endemicity, non-outbreak hospital setting. Aliment Pharmacol Ther. 2009;29:626–34.CrossRefGoogle Scholar
  26. 26.
    Seto CT, Jeraldo P, Orenstein R, et al. Prolonged use of a proton pump inhibitor reduces microbial diversity: implications for Clostridium difficile susceptibility. Microbiome. 2014;2:42.CrossRefGoogle Scholar
  27. 27.
    Mylotte JM. Laboratory surveillance method for nosocomial Clostridium difficile diarrhea. Am J Infect Control. 1998;26:16–23.CrossRefGoogle Scholar
  28. 28.
    Hensgens MP, Goorhuis A, Dekkers OM, et al. Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. J Antimicrob Chemother. 2012;67:742–8.CrossRefGoogle Scholar
  29. 29.
    Stevens V, Dumyati G, Fine LS, et al. Cumulative antibiotic exposures over time and the risk of Clostridium difficile infection. Clin Infect Dis. 2011;53:42–8.CrossRefGoogle Scholar
  30. 30.
    Hung YP, Lee JC, Lin HJ, et al. Clinical impact of Clostridium difficile colonization. J Microbiol Immunol Infect. 2015;48:241–8.CrossRefGoogle Scholar
  31. 31.
    Dial S, Delaney JA, Barkun AN, et al. Use of gastric acid-suppressive agents and the risk of community-acquired Clostridium difficile-associated disease. JAMA. 2005;294:2989–95.CrossRefGoogle Scholar
  32. 32.
    Lewis PO, Litchfield JM, Tharp JL, et al. Risk and severity of hospital-acquired Clostridium difficile infection in patients taking proton pump inhibitors. Pharmacotherapy. 2016;36:986–93.CrossRefGoogle Scholar
  33. 33.
    Hamzat H, Sun H, Ford JC, et al. Inappropriate prescribing of proton pump inhibitors in older patients: effects of an educational strategy. Drugs Aging. 2012;29:681–90.CrossRefGoogle Scholar

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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