Treatment regimens for Helicobacter pylori

INTRODUCTION

Multiple regimens have been evaluated for Helicobacter pylori therapy in randomized controlled trials [1-5]. Despite the number of studies, the optimal therapeutic regimen has not yet been defined. The treatment regimen that is selected must be effective, but considerations such as cost, side effects, and ease of administration should also be taken into account. (See "Indications and diagnostic tests for Helicobacter pylori infection", section on 'When to test'.)

This topic review will discuss treatment regimens for H. pylori. The indications and diagnostic tests for H. pylori infection, as well as the bacteriology and epidemiology, are discussed elsewhere. (See "Indications and diagnostic tests for Helicobacter pylori infection" and "Bacteriology and epidemiology of Helicobacter pylori infection".)

INITIAL THERAPY

Triple therapy with a proton pump inhibitor (PPI) should be used in areas where clarithromycin resistance is low (<15 percent). In the United States, given the limited information on antimicrobial resistance rates, we generally begin treatment with triple therapy with a PPI [6]. However, in patients with recent or repeated exposure to clarithromycin or metronidazole or when clarithromycin resistance is high (≥15 percent), quadruple therapy should be used to treat H. pylori (table 1) [7-13].

Triple therapy — The regimen most commonly recommended for first line treatment of H. pylori is triple therapy with a PPI (lansoprazole 30 mg twice daily, omeprazole 20 mg twice daily, pantoprazole 40 mg twice daily, rabeprazole 20 mg twice daily, or esomeprazole 40 mg once daily), amoxicillin (1 g twice daily), and clarithromycin (500 mg twice daily) for 7 to 14 days. We suggest treatment for 10 days to two weeks.

A longer duration of treatment (14 versus 7 days) may be more effective in curing infection but this remains controversial [14-16]. A meta-analysis suggested that extension of PPI-based triple therapy from 7 to 14 days was associated with a 5 percent increase in eradication rates [16]. Most studies included were based upon amoxicillin-based triple therapy.

             

Subscribers log in here

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information or to purchase a personal subscription, click below on the option that best describes you:
Literature review current through: Oct 2014. | This topic last updated: Sep 25, 2014.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2014 UpToDate, Inc.
References
Top
  1. Qasim A, Sebastian S, Thornton O, et al. Rifabutin- and furazolidone-based Helicobacter pylori eradication therapies after failure of standard first- and second-line eradication attempts in dyspepsia patients. Aliment Pharmacol Ther 2005; 21:91.
  2. Gatta L, Zullo A, Perna F, et al. A 10-day levofloxacin-based triple therapy in patients who have failed two eradication courses. Aliment Pharmacol Ther 2005; 22:45.
  3. Gisbert JP, Gonzalez L, Calvet X. Systematic review and meta-analysis: proton pump inhibitor vs. ranitidine bismuth citrate plus two antibiotics in Helicobacter pylori eradication. Helicobacter 2005; 10:157.
  4. Fischbach LA, van Zanten S, Dickason J. Meta-analysis: the efficacy, adverse events, and adherence related to first-line anti-Helicobacter pylori quadruple therapies. Aliment Pharmacol Ther 2004; 20:1071.
  5. Graham DY, Hammoud F, El-Zimaity HM, et al. Meta-analysis: proton pump inhibitor or H2-receptor antagonist for Helicobacter pylori eradication. Aliment Pharmacol Ther 2003; 17:1229.
  6. 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.
  7. Chey WD, Wong BC, Practice Parameters Committee of the American College of Gastroenterology. American College of Gastroenterology guideline on the management of Helicobacter pylori infection. Am J Gastroenterol 2007; 102:1808.
  8. Malfertheiner P, Megraud F, O'Morain C, et al. Current concepts in the management of Helicobacter pylori infection: the Maastricht III Consensus Report. Gut 2007; 56:772.
  9. Malfertheiner P, Megraud F, O'Morain CA, et al. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut 2012; 61:646.
  10. Graham DY, Shiotani A. Which Therapy for Helicobacter pylori Infection? Gastroenterology 2012; 143:10.
  11. Tepes B, O'Connor A, Gisbert JP, O'Morain C. Treatment of Helicobacter pylori infection 2012. Helicobacter 2012; 17 Suppl 1:36.
  12. Horvath A, Dziechciarz P, Szajewska H. Meta-analysis: sequential therapy for Helicobacter pylori eradication in children. Aliment Pharmacol Ther 2012; 36:534.
  13. Gisbert JP, Calvet X. Review article: the effectiveness of standard triple therapy for Helicobacter pylori has not changed over the last decade, but it is not good enough. Aliment Pharmacol Ther 2011; 34:1255.
  14. Fischbach LA, Goodman KJ, Feldman M, Aragaki C. Sources of variation of Helicobacter pylori treatment success in adults worldwide: a meta-analysis. Int J Epidemiol 2002; 31:128.
  15. Vakil N, Connor J. Helicobacter pylori eradication: equivalence trials and the optimal duration of therapy. Am J Gastroenterol 2005; 100:1702.
  16. Fuccio L, Minardi ME, Zagari RM, et al. Meta-analysis: duration of first-line proton-pump inhibitor based triple therapy for Helicobacter pylori eradication. Ann Intern Med 2007; 147:553.
  17. Gisbert JP, González L, Calvet X, et al. Proton pump inhibitor, clarithromycin and either amoxycillin or nitroimidazole: a meta-analysis of eradication of Helicobacter pylori. Aliment Pharmacol Ther 2000; 14:1319.
  18. Vakil N. Helicobacter pylori: factors affecting eradication and recurrence. Am J Gastroenterol 2005; 100:2393.
  19. McColl KE. Clinical practice. Helicobacter pylori infection. N Engl J Med 2010; 362:1597.
  20. Wang Z, Wu S. Doxycycline-based quadruple regimen versus routine quadruple regimen for rescue eradication of Helicobacter pylori: an open-label control study in Chinese patients. Singapore Med J 2012; 53:273.
  21. Akyildiz M, Akay S, Musoglu A, et al. The efficacy of ranitidine bismuth citrate, amoxicillin and doxycycline or tetracycline regimens as a first line treatment for Helicobacter pylori eradication. Eur J Intern Med 2009; 20:53.
  22. Fischbach L, Evans EL. Meta-analysis: the effect of antibiotic resistance status on the efficacy of triple and quadruple first-line therapies for Helicobacter pylori. Aliment Pharmacol Ther 2007; 26:343.
  23. Sun Q, Liang X, Zheng Q, et al. High efficacy of 14-day triple therapy-based, bismuth-containing quadruple therapy for initial Helicobacter pylori eradication. Helicobacter 2010; 15:233.
  24. Laine L, Hunt R, El-Zimaity H, et al. Bismuth-based quadruple therapy using a single capsule of bismuth biskalcitrate, metronidazole, and tetracycline given with omeprazole versus omeprazole, amoxicillin, and clarithromycin for eradication of Helicobacter pylori in duodenal ulcer patients: a prospective, randomized, multicenter, North American trial. Am J Gastroenterol 2003; 98:562.
  25. Malfertheiner P, Bazzoli F, Delchier JC, et al. Helicobacter pylori eradication with a capsule containing bismuth subcitrate potassium, metronidazole, and tetracycline given with omeprazole versus clarithromycin-based triple therapy: a randomised, open-label, non-inferiority, phase 3 trial. Lancet 2011; 377:905.
  26. Katelaris PH, Forbes GM, Talley NJ, Crotty B. A randomized comparison of quadruple and triple therapies for Helicobacter pylori eradication: The QUADRATE Study. Gastroenterology 2002; 123:1763.
  27. Lara LF, Cisneros G, Gurney M, et al. One-day quadruple therapy compared with 7-day triple therapy for Helicobacter pylori infection. Arch Intern Med 2003; 163:2079.
  28. Basu PP, Rayapudi K, Pacana T, et al. A randomized study comparing levofloxacin, omeprazole, nitazoxanide, and doxycycline versus triple therapy for the eradication of Helicobacter pylori. Am J Gastroenterol 2011; 106:1970.
  29. Moayyedi P, Malfertheiner P. Editorial: Sequential therapy for eradication of Helicobacter pylori: a new guiding light or a false dawn? Am J Gastroenterol 2009; 104:3081.
  30. Federico A, Nardone G, Gravina AG, et al. Efficacy of 5-day levofloxacin-containing concomitant therapy in eradication of Helicobacter pylori infection. Gastroenterology 2012; 143:55.
  31. Wu DC, Hsu PI, Wu JY, et al. Sequential and concomitant therapy with four drugs is equally effective for eradication of H pylori infection. Clin Gastroenterol Hepatol 2010; 8:36.
  32. McNicholl AG, Marin AC, Molina-Infante J, et al. Randomised clinical trial comparing sequential and concomitant therapies for Helicobacter pylori eradication in routine clinical practice. Gut 2014; 63:244.
  33. Zullo A, De Francesco V, Hassan C, et al. The sequential therapy regimen for Helicobacter pylori eradication: a pooled-data analysis. Gut 2007; 56:1353.
  34. Jafri NS, Hornung CA, Howden CW. Meta-analysis: sequential therapy appears superior to standard therapy for Helicobacter pylori infection in patients naive to treatment. Ann Intern Med 2008; 148:923.
  35. Vaira D, Zullo A, Vakil N, et al. Sequential therapy versus standard triple-drug therapy for Helicobacter pylori eradication: a randomized trial. Ann Intern Med 2007; 146:556.
  36. Kim YS, Kim SJ, Yoon JH, et al. Randomised clinical trial: the efficacy of a 10-day sequential therapy vs. a 14-day standard proton pump inhibitor-based triple therapy for Helicobacter pylori in Korea. Aliment Pharmacol Ther 2011; 34:1098.
  37. Gatta L, Vakil N, Leandro G, et al. Sequential therapy or triple therapy for Helicobacter pylori infection: systematic review and meta-analysis of randomized controlled trials in adults and children. Am J Gastroenterol 2009; 104:3069.
  38. Greenberg ER, Anderson GL, Morgan DR, et al. 14-day triple, 5-day concomitant, and 10-day sequential therapies for Helicobacter pylori infection in seven Latin American sites: a randomised trial. Lancet 2011; 378:507.
  39. Liou JM, Chen CC, Chen MJ, et al. Sequential versus triple therapy for the first-line treatment of Helicobacter pylori: a multicentre, open-label, randomised trial. Lancet 2013; 381:205.
  40. Morgan DR, Torres J, Sexton R, et al. Risk of recurrent Helicobacter pylori infection 1 year after initial eradication therapy in 7 Latin American communities. JAMA 2013; 309:578.
  41. Romano M, Cuomo A, Gravina AG, et al. Empirical levofloxacin-containing versus clarithromycin-containing sequential therapy for Helicobacter pylori eradication: a randomised trial. Gut 2010; 59:1465.
  42. Albrecht P, Kotowska M, Szajewska H. Sequential therapy compared with standard triple therapy for Helicobacter pylori eradication in children: a double-blind, randomized, controlled trial. J Pediatr 2011; 159:45.
  43. Bontems P, Kalach N, Oderda G, et al. Sequential therapy versus tailored triple therapies for Helicobacter pylori infection in children. J Pediatr Gastroenterol Nutr 2011; 53:646.
  44. Vakil N. Primary and secondary treatment for Helicobacter pylori in the United States. Rev Gastroenterol Disord 2005; 5:67.
  45. Hojo M, Miwa H, Nagahara A, Sato N. Pooled analysis on the efficacy of the second-line treatment regimens for Helicobacter pylori infection. Scand J Gastroenterol 2001; 36:690.
  46. Kearney DJ. Retreatment of Helicobacter pylori infection after initial treatment failure. Am J Gastroenterol 2001; 96:1335.
  47. Malfertheiner P, Leodolter A, Peitz U. Cure of Helicobacter pylori-associated ulcer disease through eradication. Baillieres Best Pract Res Clin Gastroenterol 2000; 14:119.
  48. Lamouliatte H, Mégraud 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.
  49. Megraud F, Coenen S, Versporten A, et al. Helicobacter pylori resistance to antibiotics in Europe and its relationship to antibiotic consumption. Gut 2013; 62:34.
  50. Chi CH, Lin CY, Sheu BS, et al. Quadruple therapy containing amoxicillin and tetracycline is an effective regimen to rescue failed triple therapy by overcoming the antimicrobial resistance of Helicobacter pylori. Aliment Pharmacol Ther 2003; 18:347.
  51. Dore MP, Marras L, Maragkoudakis E, et al. Salvage therapy after two or more prior Helicobacter pylori treatment failures: the super salvage regimen. Helicobacter 2003; 8:307.
  52. Bilardi C, Dulbecco P, Zentilin P, et al. A 10-day levofloxacin-based therapy in patients with resistant Helicobacter pylori infection: a controlled trial. Clin Gastroenterol Hepatol 2004; 2:997.
  53. Saad RJ, Schoenfeld P, Kim HM, Chey WD. Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis. Am J Gastroenterol 2006; 101:488.
  54. Gisbert JP, Castro-Fernández M, Bermejo F, et al. Third-line rescue therapy with levofloxacin after two H. pylori treatment failures. Am J Gastroenterol 2006; 101:243.
  55. Gisbert JP, Bermejo F, Castro-Fernández M, et al. Second-line rescue therapy with levofloxacin after H. pylori treatment failure: a Spanish multicenter study of 300 patients. Am J Gastroenterol 2008; 103:71.
  56. Jodlowski TZ, Lam S, Ashby CR Jr. Emerging therapies for the treatment of Helicobacter pylori infections. Ann Pharmacother 2008; 42:1621.
  57. Perri F, Festa V, Clemente R, et al. Randomized study of two "rescue" therapies for Helicobacter pylori-infected patients after failure of standard triple therapies. Am J Gastroenterol 2001; 96:58.
  58. Gisbert JP, Castro-Fernandez M, Perez-Aisa A, et al. Fourth-line rescue therapy with rifabutin in patients with three Helicobacter pylori eradication failures. Aliment Pharmacol Ther 2012; 35:941.
  59. Miehlke S, Schneider-Brachert W, Kirsch C, et al. One-week once-daily triple therapy with esomeprazole, moxifloxacin, and rifabutin for eradication of persistent Helicobacter pylori resistant to both metronidazole and clarithromycin. Helicobacter 2008; 13:69.
  60. van der Hulst RW, Keller JJ, Rauws EA, Tytgat GN. Treatment of Helicobacter pylori infection: a review of the world literature. Helicobacter 1996; 1:6.
  61. Graham DY, Lew GM, Malaty HM, et al. Factors influencing the eradication of Helicobacter pylori with triple therapy. Gastroenterology 1992; 102:493.
  62. Noach LA, Langenberg WL, Bertola MA, et al. Impact of metronidazole resistance on the eradication of Helicobacter pylori. Scand J Infect Dis 1994; 26:321.
  63. Lind T, Mégraud F, Unge P, et al. The MACH2 study: role of omeprazole in eradication of Helicobacter pylori with 1-week triple therapies. Gastroenterology 1999; 116:248.
  64. Vakil N, Hahn B, McSorley D. Clarithromycin-resistant Helicobacter pylori in patients with duodenal ulcer in the United States. Am J Gastroenterol 1998; 93:1432.
  65. Osato MS, Reddy R, Reddy SG, et al. Pattern of primary resistance of Helicobacter pylori to metronidazole or clarithromycin in the United States. Arch Intern Med 2001; 161:1217.
  66. 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.
  67. De Francesco V, Margiotta M, Zullo A, et al. Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. Ann Intern Med 2006; 144:94.
  68. McMahon BJ, Hennessy TW, Bensler JM, et al. The relationship among previous antimicrobial use, antimicrobial resistance, and treatment outcomes for Helicobacter pylori infections. Ann Intern Med 2003; 139:463.
  69. Windsor HM, Ho GY, Marshall BJ. Successful recovery of H. pylori from rapid urease tests (CLO tests). Am J Gastroenterol 1999; 94:3181.
  70. de Boer WA, Tytgat GN. The best therapy for Helicobacter pylori infection: should efficacy or side-effect profile determine our choice? Scand J Gastroenterol 1995; 30:401.
  71. Nseir W, Diab H, Mahamid M, et al. Randomised clinical trial: simvastatin as adjuvant therapy improves significantly the Helicobacter pylori eradication rate--a placebo-controlled study. Aliment Pharmacol Ther 2012; 36:231.
  72. Cindoruk M, Erkan G, Karakan T, et al. Efficacy and safety of Saccharomyces boulardii in the 14-day triple anti-Helicobacter pylori therapy: a prospective randomized placebo-controlled double-blind study. Helicobacter 2007; 12:309.
  73. Song MJ, Park DI, Park JH, et al. The effect of probiotics and mucoprotective agents on PPI-based triple therapy for eradication of Helicobacter pylori. Helicobacter 2010; 15:206.
  74. Franceschi F, Cazzato A, Nista EC, et al. Role of probiotics in patients with Helicobacter pylori infection. Helicobacter 2007; 12 Suppl 2:59.
  75. Szajewska H, Horvath A, Piwowarczyk A. Meta-analysis: the effects of Saccharomyces boulardii supplementation on Helicobacter pylori eradication rates and side effects during treatment. Aliment Pharmacol Ther 2010; 32:1069.
  76. Mahadevan U, Kane S. American gastroenterological association institute technical review on the use of gastrointestinal medications in pregnancy. Gastroenterology 2006; 131:283.
  77. Golberg D, Szilagyi A, Graves L. Hyperemesis gravidarum and Helicobacter pylori infection: a systematic review. Obstet Gynecol 2007; 110:695.
  78. Mansour GM, Nashaat EH. Role of Helicobacter pylori in the pathogenesis of hyperemesis gravidarum. Arch Gynecol Obstet 2011; 284:843.