Research progress of high-dose dual therapy of amoxicillin and proton pump inhibitors in eradication of <i>Helicobacter pylori</i>_West China Medical Journal

Authors：

ZHENG Xulin ^1,2 , YU Xinxin ³ ,  CHEN Yongjun ²

1. Graduate School of North Sichuan Medical College, Nanchong, Sichuan 637000, P. R. China;
2. Gastrointestinal Endoscopy Center, Suining Central Hospital, Suining, Sichuan 629000, P. R. China;
3. First Department of Respiratory and Critical Care Medicine, Suining Central Hospital, Suining, Sichuan 629000, P. R. China;

Corresponding author：

CHEN Yongjun, Email: snszxyy@126.com

Keywords：

Amoxicillin; high-dose dual therapy; Helicobacter pylori

DOI：

10.7507/1002-0179.202109067

Video：

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Helicobacter pylori (HP) infection is common worldwide, and the first-line eradication regimen recommended by domestic and foreign guidelines faces many challenges in practical application. In order to further improve the HP eradication rate and patient compliance, problems such as increased antibiotic resistance, a wide variety of drugs, and obvious drug side effects need to be solved urgently. In recent years, high-dose dual therapy of amoxicillin combined with proton pump inhibitor have achieved good eradication effect in the treatment of HP infection. This article reviews the action mechanism, safety and therapeutic effect of high-dose dual therapy, aiming to provide a reference for clinical diagnosis and treatment.

Citation： ZHENG Xulin, YU Xinxin, CHEN Yongjun. Research progress of high-dose dual therapy of amoxicillin and proton pump inhibitors in eradication of Helicobacter pylori. West China Medical Journal, 2022, 37(9): 1410-1413. doi: 10.7507/1002-0179.202109067 Copy

1.	Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology, 2017, 153(2): 420-429.
2.	Burucoa C, Axon A. Epidemiology of Helicobacter pylori infection. Helicobacter, 2017, 22(Suppl 1): e12403.
3.	Liu WZ, Xie Y, Lu H, et al. Fifth Chinese national consensus report on the management of Helicobacter pylori infection. Helicobacter, 2018, 23(2): e12475.
4.	Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med, 2018, 378(12): 1085-1095.
5.	Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology, 2016, 151(1): 51-69.e14.
6.	Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut, 2017, 66(1): 6-30.
7.	Unge P, Gad A, Gnarpe H, et al. Does omeprazole improve antimicrobial therapy directed towards gastric Campylobacter pylori in patients with antral gastritis? A pilot study. Scand J Gastroenterol Suppl, 1989, 167: 49-54.
8.	Zhu YJ, Zhang Y, Wang TY, et al. High dose PPI-amoxicillin dual therapy for the treatment of Helicobacter pylori infection: a systematic review with meta-analysis. Therap Adv Gastroenterol, 2020, 13: 1756284820937115.
9.	Yang X, Wang JX, Han SX, et al. High dose dual therapy versus bismuth quadruple therapy for Helicobacter pylori eradication treatment: a systematic review and meta-analysis. Medicine (Baltimore), 2019, 98(7): e14396.
10.	Li C, Shi Y, Suo B, et al. PPI-amoxicillin dual therapy four times daily is superior to guidelines recommended regimens in the Helicobacter pylori eradication therapy within Asia: a systematic review and meta-analysis. Helicobacter, 2021, 26(4): e12816.
11.	Kleveland PM, Waldum HL, Brenna E, et al. Relationship between the efficacy of amoxicillin and intragastric pH for the treatment of Helicobacter pylori infection. Helicobacter, 1997, 2(3): 144-148.
12.	Marcus EA, Inatomi N, Nagami GT, et al. The effects of varying acidity on Helicobacter pylori growth and the bactericidal efficacy of ampicillin. Aliment Pharmacol Ther, 2012, 36(10): 972-979.
13.	Savoldi A, Carrara E, Graham DY, et al. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in world health organization regions. Gastroenterology, 2018, 155(5): 1372-1382.e17.
14.	Shiota S, Reddy R, Alsarraj A, et al. Antibiotic resistance of Helicobacter pylori among male United States veterans. Clin Gastroenterol Hepatol, 2015, 13(9): 1616-1624.
15.	Schwartz H, Krause R, Sahba B, et al. Triple versus dual therapy for eradicating Helicobacter pylori and preventing ulcer recurrence: a randomized, double-blind, multicenter study of lansoprazole, clarithromycin, and/or amoxicillin in different dosing regimens. Am J Gastroenterol, 1998, 93(4): 584-590.
16.	Kim SY, Jung SW, Kim JH, et al. Effectiveness of three times daily lansoprazole/amoxicillin dual therapy for Helicobacter pylori infection in Korea. Br J Clin Pharmacol, 2012, 73(1): 140-143.
17.	Sapmaz F, Kalkan IH, Atasoy P, et al. A non-inferiority study: modified dual therapy consisting higher doses of rabeprazole is as successful as standard quadruple therapy in eradication of Helicobacter pylori. Am J Ther, 2017, 24(4): e393-e398.
18.	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(11): 622-627.
19.	Öztürk K, Kurt Ö, Çelebi G, et al. High-dose dual therapy is effective as first-line treatment for Helicobacter pylori infection. Turk J Gastroenterol, 2020, 31(3): 234-238.
20.	Zullo A, Ridola L, Francesco VD, et al. High-dose esomeprazole and amoxicillin dual therapy for first-line Helicobacter pylori eradication: a proof of concept study. Ann Gastroenterol, 2015, 28(4): 448-451.
21.	Yu L, Luo L, Long X, et al. High-dose PPI-amoxicillin dual therapy with or without bismuth for first-line Helicobacter pylori therapy: a randomized trial. Helicobacter, 2019, 24(4): e12596.
22.	Murakami K, Furuta T, Ando T, et al. Multi-center randomized controlled study to establish the standard third-line regimen for Helicobacter pylori eradication in Japan. J Gastroenterol, 2013, 48(10): 1128-1135.
23.	Hu JL, Yang J, Zhou YB, et al. Optimized high-dose amoxicillin-proton-pump inhibitor dual therapies fail to achieve high cure rates in China. Saudi J Gastroenterol, 2017, 23(5): 275-280.
24.	Hwong-Ruey Leow A, Chang JV, Goh KL. Searching for an optimal therapy for H pylori eradication: high-dose proton-pump inhibitor dual therapy with amoxicillin vs. standard triple therapy for 14 days. Helicobacter, 2020, 25(5): e12723.
25.	Zhang Y, Zhu YJ, Zhao Z, et al. Efficacy of modified esomeprazole-amoxicillin dual therapies for Helicobacter pylori infection: an open-label, randomized trial. Eur J Gastroenterol Hepatol, 2020, 32(5): 563-568.
26.	Song Z, Zhou L, Xue Y, et al. A comparative study of 14-day dual therapy (esomeprazole and amoxicillin four times daily) and triple plus bismuth therapy for first-line Helicobacter pylori infection eradication: a randomized trial. Helicobacter, 2020, 25(6): e12762.
27.	Yang J, Zhang Y, Fan L, et al. Eradication efficacy of modified dual therapy compared with bismuth-containing quadruple therapy as a first-line treatment of Helicobacter pylori. Am J Gastroenterol, 2019, 114(3): 437-445.
28.	Tai WC, Liang CM, Kuo CM, et al. A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy regimen achieves a high eradication rate as first-line anti-Helicobacter pylori treatment in Taiwan: a prospective randomized trial. J Antimicrob Chemother, 2019, 74(6): 1718-1724.
29.	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(4): 310-319.
30.	Miehlke S, Hansky K, Schneider-Brachert W, et al. Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Aliment Pharmacol Ther, 2006, 24(2): 395-403.
31.	Shirai N, Sugimoto M, Kodaira C, et al. Dual therapy with high doses of rabeprazole and amoxicillin versus triple therapy with rabeprazole, amoxicillin, and metronidazole as a rescue regimen for Helicobacter pylori infection after the standard triple therapy. Eur J Clin Pharmacol, 2007, 63(8): 743-749.
32.	Nishizawa T, Suzuki H, Maekawa T, et al. Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction. World J Gastroenterol, 2012, 18(21): 2735-2738.
33.	Gao W, Ye H, Deng X, et al. Rabeprazole-amoxicillin dual therapy as first-line treatment for H pylori eradication in special patients: a retrospective, real-life study. Helicobacter, 2020, 25(5): e12717.

1. Hooi JKY, Lai WY, Ng WK, et al. Global prevalence of Helicobacter pylori infection: systematic review and meta-analysis. Gastroenterology, 2017, 153(2): 420-429.
2. Burucoa C, Axon A. Epidemiology of Helicobacter pylori infection. Helicobacter, 2017, 22(Suppl 1): e12403.
3. Liu WZ, Xie Y, Lu H, et al. Fifth Chinese national consensus report on the management of Helicobacter pylori infection. Helicobacter, 2018, 23(2): e12475.
4. Choi IJ, Kook MC, Kim YI, et al. Helicobacter pylori therapy for the prevention of metachronous gastric cancer. N Engl J Med, 2018, 378(12): 1085-1095.
5. Fallone CA, Chiba N, van Zanten SV, et al. The Toronto consensus for the treatment of Helicobacter pylori infection in adults. Gastroenterology, 2016, 151(1): 51-69.e14.
6. Malfertheiner P, Megraud F, O’Morain CA, et al. Management of Helicobacter pylori infection-the Maastricht V/Florence Consensus Report. Gut, 2017, 66(1): 6-30.
7. Unge P, Gad A, Gnarpe H, et al. Does omeprazole improve antimicrobial therapy directed towards gastric Campylobacter pylori in patients with antral gastritis? A pilot study. Scand J Gastroenterol Suppl, 1989, 167: 49-54.
8. Zhu YJ, Zhang Y, Wang TY, et al. High dose PPI-amoxicillin dual therapy for the treatment of Helicobacter pylori infection: a systematic review with meta-analysis. Therap Adv Gastroenterol, 2020, 13: 1756284820937115.
9. Yang X, Wang JX, Han SX, et al. High dose dual therapy versus bismuth quadruple therapy for Helicobacter pylori eradication treatment: a systematic review and meta-analysis. Medicine (Baltimore), 2019, 98(7): e14396.
10. Li C, Shi Y, Suo B, et al. PPI-amoxicillin dual therapy four times daily is superior to guidelines recommended regimens in the Helicobacter pylori eradication therapy within Asia: a systematic review and meta-analysis. Helicobacter, 2021, 26(4): e12816.
11. Kleveland PM, Waldum HL, Brenna E, et al. Relationship between the efficacy of amoxicillin and intragastric pH for the treatment of Helicobacter pylori infection. Helicobacter, 1997, 2(3): 144-148.
12. Marcus EA, Inatomi N, Nagami GT, et al. The effects of varying acidity on Helicobacter pylori growth and the bactericidal efficacy of ampicillin. Aliment Pharmacol Ther, 2012, 36(10): 972-979.
13. Savoldi A, Carrara E, Graham DY, et al. Prevalence of antibiotic resistance in Helicobacter pylori: a systematic review and meta-analysis in world health organization regions. Gastroenterology, 2018, 155(5): 1372-1382.e17.
14. Shiota S, Reddy R, Alsarraj A, et al. Antibiotic resistance of Helicobacter pylori among male United States veterans. Clin Gastroenterol Hepatol, 2015, 13(9): 1616-1624.
15. Schwartz H, Krause R, Sahba B, et al. Triple versus dual therapy for eradicating Helicobacter pylori and preventing ulcer recurrence: a randomized, double-blind, multicenter study of lansoprazole, clarithromycin, and/or amoxicillin in different dosing regimens. Am J Gastroenterol, 1998, 93(4): 584-590.
16. Kim SY, Jung SW, Kim JH, et al. Effectiveness of three times daily lansoprazole/amoxicillin dual therapy for Helicobacter pylori infection in Korea. Br J Clin Pharmacol, 2012, 73(1): 140-143.
17. Sapmaz F, Kalkan IH, Atasoy P, et al. A non-inferiority study: modified dual therapy consisting higher doses of rabeprazole is as successful as standard quadruple therapy in eradication of Helicobacter pylori. Am J Ther, 2017, 24(4): e393-e398.
18. 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(11): 622-627.
19. Öztürk K, Kurt Ö, Çelebi G, et al. High-dose dual therapy is effective as first-line treatment for Helicobacter pylori infection. Turk J Gastroenterol, 2020, 31(3): 234-238.
20. Zullo A, Ridola L, Francesco VD, et al. High-dose esomeprazole and amoxicillin dual therapy for first-line Helicobacter pylori eradication: a proof of concept study. Ann Gastroenterol, 2015, 28(4): 448-451.
21. Yu L, Luo L, Long X, et al. High-dose PPI-amoxicillin dual therapy with or without bismuth for first-line Helicobacter pylori therapy: a randomized trial. Helicobacter, 2019, 24(4): e12596.
22. Murakami K, Furuta T, Ando T, et al. Multi-center randomized controlled study to establish the standard third-line regimen for Helicobacter pylori eradication in Japan. J Gastroenterol, 2013, 48(10): 1128-1135.
23. Hu JL, Yang J, Zhou YB, et al. Optimized high-dose amoxicillin-proton-pump inhibitor dual therapies fail to achieve high cure rates in China. Saudi J Gastroenterol, 2017, 23(5): 275-280.
24. Hwong-Ruey Leow A, Chang JV, Goh KL. Searching for an optimal therapy for H pylori eradication: high-dose proton-pump inhibitor dual therapy with amoxicillin vs. standard triple therapy for 14 days. Helicobacter, 2020, 25(5): e12723.
25. Zhang Y, Zhu YJ, Zhao Z, et al. Efficacy of modified esomeprazole-amoxicillin dual therapies for Helicobacter pylori infection: an open-label, randomized trial. Eur J Gastroenterol Hepatol, 2020, 32(5): 563-568.
26. Song Z, Zhou L, Xue Y, et al. A comparative study of 14-day dual therapy (esomeprazole and amoxicillin four times daily) and triple plus bismuth therapy for first-line Helicobacter pylori infection eradication: a randomized trial. Helicobacter, 2020, 25(6): e12762.
27. Yang J, Zhang Y, Fan L, et al. Eradication efficacy of modified dual therapy compared with bismuth-containing quadruple therapy as a first-line treatment of Helicobacter pylori. Am J Gastroenterol, 2019, 114(3): 437-445.
28. Tai WC, Liang CM, Kuo CM, et al. A 14 day esomeprazole- and amoxicillin-containing high-dose dual therapy regimen achieves a high eradication rate as first-line anti-Helicobacter pylori treatment in Taiwan: a prospective randomized trial. J Antimicrob Chemother, 2019, 74(6): 1718-1724.
29. 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(4): 310-319.
30. Miehlke S, Hansky K, Schneider-Brachert W, et al. Randomized trial of rifabutin-based triple therapy and high-dose dual therapy for rescue treatment of Helicobacter pylori resistant to both metronidazole and clarithromycin. Aliment Pharmacol Ther, 2006, 24(2): 395-403.
31. Shirai N, Sugimoto M, Kodaira C, et al. Dual therapy with high doses of rabeprazole and amoxicillin versus triple therapy with rabeprazole, amoxicillin, and metronidazole as a rescue regimen for Helicobacter pylori infection after the standard triple therapy. Eur J Clin Pharmacol, 2007, 63(8): 743-749.
32. Nishizawa T, Suzuki H, Maekawa T, et al. Dual therapy for third-line Helicobacter pylori eradication and urea breath test prediction. World J Gastroenterol, 2012, 18(21): 2735-2738.
33. Gao W, Ye H, Deng X, et al. Rabeprazole-amoxicillin dual therapy as first-line treatment for H pylori eradication in special patients: a retrospective, real-life study. Helicobacter, 2020, 25(5): e12717.

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