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Factors Affecting First-Line Triple Therapy of Helicobacter pylori Including CYP2C19 Genotype and Antibiotic Resistance

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Abstract

Background

Emerging evidence shows that the eradication rate of proton pump inhibitor (PPI)-based triple therapy for the first-line treatment of Helicobacter pylori (H. pylori) has decreased.

Aims

To clarify the trend of eradication rate of PPI-based triple therapy and to assess the related factors in Korea during the past decade.

Methods

We prospectively prescribed the triple regimen for seven days (PPI + amoxicillin 1.0 g + clarithromycin 500 mg, twice a day) from March 2003 to May 2013 in 2,202 H. pylori-positive patients. Antibiotic susceptibility tests were performed by the agar dilution method, and the CYP2C19 genotype was determined by the PCR method.

Results

In the past decade, the annual eradication rate showed a decreasing trend in intention-to-treat and per-protocol analyses (P = 0.001, both). The antibiotic resistance was increased to amoxicillin (7.2–17.2 %, P = 0.003) and clarithromycin (23.2–37.3 %, P = 0.010) during the study period. The poor metabolizer genotype of CYP2C19 showed a high eradication rate compared to the extensive metabolizer (86.8 vs. 78.2 %, P = 0.035). In addition, age ≥ 50 years, female gender, BMI < 25 kg/m2, amoxicillin and/or clarithromycin resistance were associated with treatment failure on univariate analysis. However, on multivariate analysis, clarithromycin resistance was the only significant factor for treatment failure (OR, 12.76; 95 % CI, 5.58–29.18; P < 0.001).

Conclusions

An increase in clarithromycin resistance has led to decreased eradication rate of first-line triple therapy, and; hence, a new strategy is needed to improve the eradication rate of H. pylori.

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References

  1. McColl KE. Clinical practice. Helicobacter pylori infection. N Engl J Med. 2010;362:1597–1604.

    Article  CAS  PubMed  Google Scholar 

  2. Malfertheiner P, Megraud F, O’Morain C, et al. Current concepts in the management of Helicobacter pylori infection–the Maastricht 2-2000 Consensus Report. Aliment Pharmacol Ther. 2002;16:167–180.

    Article  CAS  PubMed  Google Scholar 

  3. Lim SH, Kwon JW, Kim N, et al. Prevalence and risk factors of Helicobacter pylori infection in Korea: nationwide multicenter study over 13 years. BMC Gastroenterol. 2013;13:104.

    Article  PubMed Central  PubMed  Google Scholar 

  4. Chey WD, Wong BC. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol. 2007;102:1808–1825.

    Article  CAS  PubMed  Google Scholar 

  5. Graham DY, Lu H, Yamaoka Y. A report card to grade Helicobacter pylori therapy. Helicobacter. 2007;12:275–278.

    Article  PubMed  Google Scholar 

  6. Cho DK, Park SY, Kee WJ, et al. The trend of eradication rate of Helicobacter pylori infection and clinical factors that affect the eradication of first-line therapy. Korean J Gastroenterol. 2010;55:368.

    Article  PubMed  Google Scholar 

  7. Choi YS, Cheon JH, Lee JY, et al. The trend of eradication rates of first-line triple therapy for Helicobacter pylori infection: single center experience for recent eight years. Korean J Gastroenterol. 2006;48:156–161.

    PubMed  Google Scholar 

  8. Dickson EJ, Stuart RC. Genetics of response to proton pump inhibitor therapy: clinical implications. Am J Pharmacogenomics. 2003;3:303–315.

    Article  CAS  PubMed  Google Scholar 

  9. Chong E, Ensom MH. Pharmacogenetics of the proton pump inhibitors: a systematic review. Pharmacotherapy. 2003;23:460–471.

    Article  CAS  PubMed  Google Scholar 

  10. Padol S, Yuan Y, Thabane M, Padol IT, Hunt RH. The effect of CYP2C19 polymorphisms on H. pylori eradication rate in dual and triple first-line PPI therapies: a meta-analysis. Am J Gastroenterol. 2006;101:1467–1475.

    Article  CAS  PubMed  Google Scholar 

  11. van Zanten SV, Thompson K. Should the presence of polymorphisms of CYP2C19 enzymes influence the choice of the proton pump inhibitor for treatment of Helicobacter pylori infection? Am J Gastroenterol. 2006;101:1476–1478.

    Article  PubMed  Google Scholar 

  12. Lee JH, Jung HY, Choi KD, Song HJ, Lee GH, Kim JH. The Influence of CYP2C19 polymorphism on eradication of Helicobacter pylori: a prospective randomized study of lansoprazole and rabeprazole. Gut Liver. 2010;4:201–206.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  13. Kang JM, Kim N, Lee DH, et al. Effect of the CYP2C19 polymorphism on the eradication rate of Helicobacter pylori infection by 7-day triple therapy with regular proton pump inhibitor dosage. J Gastroenterol Hepatol. 2008;23:1287–1291.

    Article  CAS  PubMed  Google Scholar 

  14. Tang HL, Li Y, Hu YF, Xie HG, Zhai SD. Effects of CYP2C19 loss-of-function variants on the eradication of H. pylori infection in patients treated with proton pump inhibitor-based triple therapy regimens: a meta-analysis of randomized clinical trials. PLoS ONE. 2013;8:e62162.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  15. McNicholl AG, Linares PM, Nyssen OP, Calvet X, Gisbert JP. Meta-analysis: esomeprazole or rabeprazole vs. first-generation pump inhibitors in the treatment of Helicobacter pylori infection. Aliment Pharmacol Ther. 2012;36:414–425.

    Article  CAS  PubMed  Google Scholar 

  16. Zhao F, Wang J, Yang Y, et al. Effect of CYP2C19 genetic polymorphisms on the efficacy of proton pump inhibitor-based triple therapy for Helicobacter pylori eradication: a meta-analysis. Helicobacter. 2008;13:532–541.

    Article  PubMed  Google Scholar 

  17. Kim JM, Kim JS, Kim N, Jung HC, Song IS. Distribution of fluoroquinolone MICs in Helicobacter pylori strains from Korean patients. J Antimicrob Chemother. 2005;56:965–967.

    Article  CAS  PubMed  Google Scholar 

  18. Kim JM, Kim JS, Kim N, Kim SG, Jung HC, Song IS. Comparison of primary and secondary antimicrobial minimum inhibitory concentrations for Helicobacter pylori isolated from Korean patients. Int J Antimicrob Agents. 2006;28:6–13.

    Article  CAS  PubMed  Google Scholar 

  19. Meyer JM, Silliman NP, Wang W, et al. Risk factors for Helicobacter pylori resistance in the United States: the surveillance of H. pylori antimicrobial resistance partnership (SHARP) study, 1993–1999. Ann Intern Med. 2002;136:13–24.

    Article  PubMed  Google Scholar 

  20. Duck WM, Sobel J, Pruckler JM, et al. Antimicrobial resistance incidence and risk factors among Helicobacter pylori-infected persons, United States. Emerg Infect Dis.. 2004;10:1088–1094.

    Article  PubMed Central  PubMed  Google Scholar 

  21. Glupczynski Y, Megraud F, Lopez-Brea M, Andersen LP. European multicentre survey of in vitro antimicrobial resistance in Helicobacter pylori. Eur J Clin Microbiol Infect Dis. 2001;20:820–823.

    Article  CAS  PubMed  Google Scholar 

  22. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection–the Maastricht IV/Florence Consensus Report. Gut. 2012;61:646–664.

    Article  CAS  PubMed  Google Scholar 

  23. Horiki N, Omata F, Uemura M, et al. Annual change of primary resistance to clarithromycin among Helicobacter pylori isolates from 1996 through 2008 in Japan. Helicobacter. 2009;14:86–90.

    Article  CAS  PubMed  Google Scholar 

  24. Kim JM, Kim JS, Jung HC, Kim N, Kim YJ, Song IS. Distribution of antibiotic MICs for Helicobacter pylori strains over a 16-year period in patients from Seoul, South Korea. Antimicrob Agents Chemother. 2004;48:4843–4847.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  25. Kim JY, Kim NY, Kim SJ, et al. Regional difference of antibiotic resistance of Helicobacter pylori strains in Korea. Korean J Gastroenterol. 2011;57:221–229.

    Article  PubMed  Google Scholar 

  26. Lamouliatte H, Megraud F, Delchier JC, et al. Second-line treatment for failure to eradicate Helicobacter pylori: a randomized trial comparing four treatment strategies. Aliment Pharmacol Ther. 2003;18:791–797.

    Article  CAS  PubMed  Google Scholar 

  27. Fock KM, Katelaris P, Sugano K, et al. Second Asia-Pacific consensus guidelines for Helicobacter pylori infection. J Gastroenterol Hepatol. 2009;24:1587–1600.

    Article  PubMed  Google Scholar 

  28. Asaka M, Kato M, Takahashi S, et al. Guidelines for the management of Helicobacter pylori infection in Japan: 2009 revised edition. Helicobacter. 2010;15:1–20.

    Article  CAS  PubMed  Google Scholar 

  29. Kim SG, Jung H-K, Lee HL, et al. Guidelines for the diagnosis and treatment of Helicobacter pylori Infection in Korea, 2013 Revised Edition. Korean J Gastroenterol. 2013;62:3–26.

    Article  PubMed  Google Scholar 

  30. Kim JJ, Reddy R, Lee M, et al. Analysis of metronidazole, clarithromycin and tetracycline resistance of Helicobacter pylori isolates from Korea. J Antimicrob Chemother. 2001;47:459–461.

    Article  CAS  PubMed  Google Scholar 

  31. Gerrits MM, Schuijffel D, van Zwet AA, Kuipers EJ, Vandenbroucke-Grauls CM, Kusters JG. Alterations in penicillin-binding protein 1A confer resistance to beta-lactam antibiotics in Helicobacter pylori. Antimicrob Agents Chemother. 2002;46:2229–2233.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  32. Kim N, Kim JM, Kim CH, et al. Institutional difference of antibiotic resistance of Helicobacter pylori strains in Korea. J Clin Gastroenterol. 2006;40:683–687.

    Article  CAS  PubMed  Google Scholar 

  33. Hwang TJ, Kim N, Kim HB, et al. Change in antibiotic resistance of Helicobacter pylori strains and the effect of A2143G point mutation of 23S rRNA on the eradication of H. pylori in a single center of Korea. J Clin Gastroenterol. 2010;44:536–543.

    CAS  PubMed  Google Scholar 

  34. Suzuki T, Matsuo K, Sawaki A, et al. Systematic review and meta-analysis: importance of CagA status for successful eradication of Helicobacter pylori infection. Aliment Pharmacol Ther. 2006;24:273–280.

    Article  CAS  PubMed  Google Scholar 

  35. Treiber G, Ammon S, Klotz U. Age-dependent eradication of Helicobacter pylori with dual therapy. Aliment Pharmacol Ther. 1997;11:711–718.

    Article  CAS  PubMed  Google Scholar 

  36. Labenz J, Leverkus F, Borsch G. Omeprazole plus amoxicillin for cure of Helicobacter pylori infection. Factors influencing the treatment success. Scand J Gastroenterol. 1994;29:1070–1075.

    Article  CAS  PubMed  Google Scholar 

  37. Sjostedt S, Sagar M, Lindberg G, Wikstrom B, Nord CE, Seensalu R. Prolonged and profound acid inhibition is crucial in Helicobacter pylori treatment with a proton pump inhibitor combined with amoxicillin. Scand J Gastroenterol. 1998;33:39–43.

    Article  CAS  PubMed  Google Scholar 

  38. Perri F, Villani MR, Festa V, Quitadamo M, Andriulli A. Predictors of failure of Helicobacter pylori eradication with the standard ‘Maastricht triple therapy’. Aliment Pharmacol Ther. 2001;15:1023–1029.

    Article  CAS  PubMed  Google Scholar 

  39. Moayyedi P, Chalmers DM, Axon AT. Patient factors that predict failure of omeprazole, clarithromycin, and tinidazole to eradicate Helicobacter pylori. J Gastroenterol. 1997;32:24–27.

    Article  CAS  PubMed  Google Scholar 

  40. Blair AJ 3rd, Feldman M, Barnett C, Walsh JH, Richardson CT. Detailed comparison of basal and food-stimulated gastric acid secretion rates and serum gastrin concentrations in duodenal ulcer patients and normal subjects. J Clin Invest.. 1987;79:582–587.

    Article  PubMed Central  PubMed  Google Scholar 

  41. Kuepper-Nybelen J, Thefeld W, Rothenbacher D, Brenner H. Patterns of alcohol consumption and Helicobacter pylori infection: results of a population-based study from Germany among 6545 adults. Aliment Pharmacol Ther. 2005;21:57–64.

    Article  CAS  PubMed  Google Scholar 

  42. Sargyn M, Uygur-Bayramicli O, Sargyn H, Orbay E, Yavuzer D, Yayla A. Type 2 diabetes mellitus affects eradication rate of Helicobacter pylori. World J Gastroenterol. 2003;9:1126–1128.

    PubMed  Google Scholar 

  43. Osawa H, Kawakami M, Fujii M, et al. Helicobacter pylori infection and coronary heart disease in Japanese patients. Cardiology. 2001;95:14–19.

    Article  CAS  PubMed  Google Scholar 

  44. Aydemir S, Boyacioglu S, Gur G, et al. Helicobacter pylori infection in hemodialysis patients: susceptibility to amoxicillin and clarithromycin. World J Gastroenterol. 2005;11:842–845.

    CAS  PubMed  Google Scholar 

  45. Jung SW, Lee SW, Hyun JJ, et al. Efficacy of Helicobacter pylori eradication therapy in chronic liver disease. Dig Liver Dis. 2009;41:134–140.

    Article  CAS  PubMed  Google Scholar 

  46. Gencer M, Ceylan E, Yildiz Zeyrek F, Aksoy N. Helicobacter pylori seroprevalence in patients with chronic obstructive pulmonary disease and its relation to pulmonary function tests. Respiration. 2007;74:170–175.

    Article  CAS  PubMed  Google Scholar 

  47. Hsu PI, Lai KH, Lin CK, et al. A prospective randomized trial of esomeprazole- versus pantoprazole-based triple therapy for Helicobacter pylori eradication. Am J Gastroenterol. 2005;100:2387–2392.

    Article  CAS  PubMed  Google Scholar 

  48. Wu IC, Wu DC, Hsu PI, et al. Rabeprazole- versus esomeprazole-based eradication regimens for H. pylori infection. Helicobacter. 2007;12:633–637.

    Article  CAS  PubMed  Google Scholar 

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Acknowledgments

The authors are indebted to J. Patrick Barron, Professor Emeritus, Tokyo Medical University and Adjunct Professor, Seoul National University Bundang Hospital for his pro bono editing of this manuscript. This work was supported by a grant from the National Research Foundation of Korea (NRF) funded by the Korean Government (2012R1A1B5002680).

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Authors and Affiliations

  1. Department of Internal Medicine, Seoul National University Bundang Hospital, 82 Gumi-ro, 173 Beon-gil, Bundang-gu, Seongnam, Gyeonggi-do, 463-707, South Korea

    Ju Yup Lee, Nayoung Kim, Min Soo Kim, Yoon Jin Choi, Jung Won Lee, Hyuk Yoon, Cheol Min Shin, Young Soo Park & Dong Ho Lee

  2. Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

    Nayoung Kim, Dong Ho Lee & Hyun Chae Jung

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  1. Ju Yup Lee
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Correspondence to Nayoung Kim.

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Lee, J.Y., Kim, N., Kim, M.S. et al. Factors Affecting First-Line Triple Therapy of Helicobacter pylori Including CYP2C19 Genotype and Antibiotic Resistance. Dig Dis Sci 59, 1235–1243 (2014). https://doi.org/10.1007/s10620-014-3093-7

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  • DOI: https://doi.org/10.1007/s10620-014-3093-7

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