Skip to main content
SpringerLink
Log in

Helicobacter pylori Eradication with Proton Pump Inhibitors or Potassium-Competitive Acid Blockers: The Effect of Clarithromycin Resistance

  • Original Article
  • Published:
Digestive Diseases and Sciences Aims and scope Submit manuscript

Abstract

Background

Vonoprazan is a novel potassium-competitive acid blocker (P-CAB) recently approved for Helicobacter pylori eradication therapy in Japan.

Aims

To compare PPI- and P-CAP-containing triple therapy and vonoprazan-based triple therapy.

Methods

Two hundred ninety-five initial subjects received a PPI-containing triple therapy; the next 125 subjects received vonoprazan-containing triple therapy. Two sequential groups received 7-day eradication regimens consisting of amoxicillin 750 mg, clarithromycin 200 mg both twice a day with standard dose PPI or vonoprazan (20 mg) each twice daily. H. pylori eradication was confirmed by a 13C-UBT. Clarithromycin susceptibility was evaluated by 23S rRNA PCR.

Results

Population cure rates with clarithromycin susceptible strains were 89.6 versus 100 % for PPI and vonoprazan therapies, respectively. Cure rates with resistant strains were 40.2 % with PPI therapy versus 76.1 % with vonoprazan triple therapy. There was no difference in side effects.

Conclusions

Although 7-day P-CAB triple therapy was superior to 7-day PPI triple therapy, neither was highly effective, or can be recommended, in the presence of clarithromycin-resistant infections.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Asaka M, Mabe K. Strategies for eliminating death from gastric cancer in Japan. Proc Jpn Acad Ser B Phys Biol Sci. 2014;90:251–258.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Maeda S, Yoshida H, Ogura K, Kanai F, Shiratori Y, Omata M. Helicobacter pylori specific nested PCR assay for the detection of 23S rRNA mutation associated with clarithromycin resistance. Gut. 1998;43:317–321.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Melake NA, Shaker GH, Salama MA. Incidence of Helicobacter pylori infection and their clarithromycin-resistant strains in otitis media with effusion regarding phenotypic and genotypic studies. Saudi Pharm J: SPJ.. 2012;20:345–353.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Graham DY, Fischbach L. Helicobacter pylori treatment in the era of increasing antibiotic resistance. Gut. 2010;59:1143–1153.

    Article  CAS  PubMed  Google Scholar 

  5. Kim SY, Choi DJ, Chung JW. Antibiotic treatment for Helicobacter pylori: is the end coming? World J Gastrointest Pharmacol Ther. 2015;6:183–198.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Megraud F, Benejat L, Benejat L, Ontsira Ngoyi EN, Lehours P. Molecular approaches to identify Helicobacter pylori antimicrobial resistance. Gastroenterol Clin North Am. 2015;44:577–596.

    Article  PubMed  Google Scholar 

  7. Shin JM, Inatomi N, Munson K, et al. Characterization of a novel potassium-competitive acid blocker of the gastric H,K-ATPase, 1-[5-(2-fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438). J Pharmacol Exp Ther. 2011;339:412–420.

    Article  Google Scholar 

  8. Hori Y, Imanishi A, Matsukawa J, et al. 1-[5-(2-Fluorophenyl)-1-(pyridin-3-ylsulfonyl)-1H-pyrrol-3-yl]-N-methylmethanamine monofumarate (TAK-438), a novel and potent potassium-competitive acid blocker for the treatment of acid-related diseases. J Pharmacol Exp Ther. 2010;335:231–238.

    Article  CAS  PubMed  Google Scholar 

  9. Matsukawa J, Hori Y, Nishida H, Kajino M, Inatomi N. A comparative study on the modes of action of TAK-438, a novel potassium-competitive acid blocker, and lansoprazole in primary cultured rabbit gastric glands. Biochem Pharmacol. 2011;81:1145–1151.

    Article  CAS  PubMed  Google Scholar 

  10. Murakami K, Sakurai Y, Shiino M, Funao N, Nishimura A, Asaka M. Vonoprazan, a novel potassium-competitive acid blocker, as a component of first-line and second-line triple therapy for Helicobacter pylori eradication: a phase III, randomised, double-blind study. Gut. 2016;65:1439–1446.

  11. Matsumoto H, Shiotani A, Nishibayashi H, et al. Molecular detection of H. pylori using adherent gastric mucous to biopsy forceps. Helicobacter. 2016. doi:10.1111/hel.12310.

  12. Uotani T, Graham DY. Diagnosis of Helicobacter pylori using the rapid urease test. Ann Transl Med. 2015;3:9.

    PubMed  PubMed Central  Google Scholar 

  13. Graham DY. Vonoprazan Helicobacter pylori eradication therapy: ethical and interpretation issues. Gut 2016. doi:10.1136/gutjnl-2016-311796.

  14. Kirchheiner J, Glatt S, Fuhr U, et al. Relative potency of proton-pump inhibitors-comparison of effects on intragastric pH. Eur J Clin Pharmacol. 2009;65:19–31.

    Article  CAS  PubMed  Google Scholar 

  15. Yuan Y, Ford AC, Khan KJ, et al. Optimum duration of regimens for Helicobacter pylori eradication. Cochrane Database Syst Rev. 2013;12:Cd008337.

    PubMed  Google Scholar 

  16. Nishizawa T, Maekawa T, Watanabe N, et al. Clarithromycin versus metronidazole as first-line Helicobacter pylori eradication: a multicenter, prospective, randomized controlled study in Japan. J Clin Gastroenterol. 2015;49:468–471.

    CAS  PubMed  Google Scholar 

  17. Hori K, Miwa H, Matsumoto T. Efficacy of 2-week, second-line Helicobacter pylori eradication therapy using rabeprazole, amoxicillin, and metronidazole for the Japanese population. Helicobacter. 2011;16:234–240.

    Article  CAS  PubMed  Google Scholar 

  18. Savarino V, Sandro Mela G, Zentilin P, Vigneri S, Celle G. Acid inhibition and amoxicillin activity against Helicobacter pylori. Am J Gastroenterol. 1993;88:1975–1976.

    CAS  PubMed  Google Scholar 

  19. Furuta T, Shirai N, Kodaira M, et al. Pharmacogenomics-based tailored versus standard therapeutic regimen for eradication of H. pylori. Clin Pharmacol Ther. 2007;81:521–528.

    Article  CAS  PubMed  Google Scholar 

  20. Marcus EA, Inatomi N, Nagami GT, Sachs G, Scott DR. The effects of varying acidity on Helicobacter pylori growth and the bactericidal efficacy of ampicillin. Aliment Pharmacol Ther. 2012;36:972–979.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Sachs G, Shin JM, Munson K, et al. Review article: the control of gastric acid and Helicobacter pylori eradication. Aliment Pharmacol Ther. 2000;14:1383–1401.

    Article  CAS  PubMed  Google Scholar 

  22. Scott D, Weeks D, Melchers K, Sachs G. The life and death of Helicobacter pylori. Gut. 1998;43:S56–S60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Graham DY, Shiotani A. New concepts of resistance in the treatment of Helicobacter pylori infections. Nat Clin Pract Gastroenterol Hepatol. 2008;5:321–331.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yang JC, Lin CJ, Wang HL, et al. High-dose dual therapy is superior to standard first-line or rescue therapy for Helicobacter pylori infection. Clin Gastroenterol Hepatol. 2015;13:895.e895–905.e895.

    Google Scholar 

  25. Shin JM, Sachs G. Long lasting inhibitors of the gastric H,K-ATPase. Expert Rev Clin Pharmacol. 2009;2:461–468.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Hori Y, Matsukawa J, Takeuchi T, et al. A study comparing the antisecretory effect of TAK-438, a novel potassium-competitive acid blocker, with lansoprazole in animals. J Pharmacol Exp Ther. 2011;337:797–804.

    Article  CAS  PubMed  Google Scholar 

  27. Graham DY. Hp-normogram (normo-graham) for assessing the outcome of H. pylori therapy: effect of resistance, duration, and CYP2C19 genotype. Helicobacter. 2016;21:85–90.

    Article  PubMed  Google Scholar 

  28. Dore MP, Lu H, Graham DY. Role of bismuth in improving Helicobacter pylori eradication with triple therapy. Gut. 2016;65:870–888.

  29. Furuta T, Graham DY. Pharmacologic aspects of eradication therapy for Helicobacter pylori infection. Gastroenterol Clin North Am. 2010;39:465–480.

    Article  PubMed  Google Scholar 

  30. Miehlke S, Kirsch C, Schneider-Brachert W, et al. A prospective, randomized study of quadruple therapy and high-dose dual therapy for treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Helicobacter. 2003;8:310–319.

    Article  CAS  PubMed  Google Scholar 

  31. Graham DY, Dore MP. Helicobacter pylori therapy: a paradigm shift. Expert Rev Anti Infect Ther. 2016;14:577–585.

    Article  CAS  PubMed  Google Scholar 

  32. Midolo PD, Turnidge JD, Munckhof WJ. Is bactericidal activity of amoxicillin against Helicobacter pylori concentration dependent? Antimicrob Agents Chemother. 1996;40:1327–1328.

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Ren L, Lu H, Li HY, et al. New dual therapy for primary treatment of Helicobacter pylori infection: a prospective randomized study in Shanghai, China. J Dig Dis. 2014;15:622–627.

    Article  CAS  PubMed  Google Scholar 

  34. Yang JC, Wang HL, Chern HD, et al. Role of omeprazole dosage and cytochrome P450 2C19 genotype in patients receiving omeprazole-amoxicillin dual therapy for Helicobacter pylori eradication. Pharmacotherapy. 2011;31:227–238.

    Article  CAS  PubMed  Google Scholar 

  35. Smith SI, Fowora MA, Lesi OA, et al. Application of stool-PCR for the diagnosis of Helicobacter pylori from stool in Nigeria—a pilot study. SpringerPlus. 2012;1:78.

    Article  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Internal Medicine, Kawasaki Medical School, 577 Matsushima, Kurashiki City, Okayama Prefecture, 701-0192, Japan

    Hiroshi Matsumoto, Akiko Shiotani, Ryo Katsumata, Minoru Fujita, Rui Nakato, Takahisa Murao, Manabu Ishii, Tomoari Kamada & Ken Haruma

  2. Department of Medicine, Michael E. DeBakey VA Medical Center, Baylor College of Medicine, Houston, TX, USA

    David Y. Graham

Authors
  1. Hiroshi Matsumoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Akiko Shiotani
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ryo Katsumata
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Minoru Fujita
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Rui Nakato
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Takahisa Murao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Manabu Ishii
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tomoari Kamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Ken Haruma
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. David Y. Graham
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Akiko Shiotani.

Ethics declarations

Conflict of interest

The authors state that they have no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Matsumoto, H., Shiotani, A., Katsumata, R. et al. Helicobacter pylori Eradication with Proton Pump Inhibitors or Potassium-Competitive Acid Blockers: The Effect of Clarithromycin Resistance. Dig Dis Sci 61, 3215–3220 (2016). https://doi.org/10.1007/s10620-016-4305-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10620-016-4305-0

Keywords

Search

Navigation