Treatment regimens for Helicobacter pylori
- Sheila E Crowe, MD, FRCPC, FACP, FACG, AGAF
Sheila E Crowe, MD, FRCPC, FACP, FACG, AGAF
- Professor of Medicine
- University of California, San Diego
Multiple antibiotic regimens have been evaluated for Helicobacter pylori therapy [1-5]. However, few regimens have consistently achieved high eradication rates. There are also limited data on H. pylori antibiotic resistance rates to guide therapy. The treatment regimen that is selected must consider local antibiotic resistance patterns (if known), previous exposure and allergies to specific antibiotics, cost, side effects, and ease of administration.
This topic will review treatment regimens for H. pylori. The bacteriology, epidemiology, and diagnostic tests for H. pylori infection are discussed elsewhere. (See "Indications and diagnostic tests for Helicobacter pylori infection" and "Bacteriology and epidemiology of Helicobacter pylori infection".)
INDICATIONS FOR TREATMENT
All patients with evidence of active infection with H. pylori should be offered treatment. Indications for testing for H. pylori infection are discussed in detail separately. (See "Indications and diagnostic tests for Helicobacter pylori infection", section on 'Indications for testing'.)
INITIAL ANTIBIOTIC THERAPY
Approach to selecting an antibiotic regimen — The choice of initial antibiotic regimen to treat H. pylori should be guided by the presence of risk factors for macrolide resistance and the presence of a penicillin allergy. In patients with risk factors for macrolide resistance, clarithromycin-based therapy should be avoided. A suggested approach to the selection of antibiotics for initial treatment of H. pylori infection is outlined in the algorithm (algorithm 1 and table 1). (See 'Clarithromycin-based therapy' below.)
Risk factors for macrolide resistance include:
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- Fallone CA, Chiba N, van Zanten SV, et al. The Toronto Consensus for the Treatment of Helicobacter pylori Infection in Adults. Gastroenterology 2016; 151:51.
- 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.
- 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.
- Malfertheiner P, Megraud F, O'Morain CA, et al. Management of Helicobacter pylori infection--the Maastricht IV/ Florence Consensus Report. Gut 2012; 61:646.
- Graham DY, Shiotani A. Which Therapy for Helicobacter pylori Infection? Gastroenterology 2012; 143:10.
- Tepes B, O'Connor A, Gisbert JP, O'Morain C. Treatment of Helicobacter pylori infection 2012. Helicobacter 2012; 17 Suppl 1:36.
- Horvath A, Dziechciarz P, Szajewska H. Meta-analysis: sequential therapy for Helicobacter pylori eradication in children. Aliment Pharmacol Ther 2012; 36:534.
- 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.
- Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG Clinical Guideline: Treatment of Helicobacter pylori Infection. Am J Gastroenterol 2017; 112:212.
- 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.
- Luther J, Higgins PD, Schoenfeld PS, et al. Empiric quadruple vs. triple therapy for primary treatment of Helicobacter pylori infection: Systematic review and meta-analysis of efficacy and tolerability. Am J Gastroenterol 2010; 105:65.
- McColl KE. Clinical practice. Helicobacter pylori infection. N Engl J Med 2010; 362:1597.
- 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.
- 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.
- 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.
- 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.
- Venerito M, Krieger T, Ecker T, et al. Meta-analysis of bismuth quadruple therapy versus clarithromycin triple therapy for empiric primary treatment of Helicobacter pylori infection. Digestion 2013; 88:33.
- 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.
- Yuan Y, Ford AC, Khan KJ, et al. Optimum duration of regimens for Helicobacter pylori eradication. Cochrane Database Syst Rev 2013; :CD008337.
- 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.
- Gisbert JP, Calvet X. Update on non-bismuth quadruple (concomitant) therapy for eradication of Helicobacter pylori. Clin Exp Gastroenterol 2012; 5:23.
- Wang B, Wang YH, Lv ZF, et al. Review: efficacy and safety of hybrid therapy for Helicobacter pylori infection: a systematic review and meta-analysis. Helicobacter 2015; 20:79.
- Li BZ, Threapleton DE, Wang JY, et al. Comparative effectiveness and tolerance of treatments for Helicobacter pylori: systematic review and network meta-analysis. BMJ 2015; 351:h4052.
- Hsu PI, Kao SS, Wu DC, et al. A Randomized Controlled Study Comparing Reverse Hybrid Therapy and Standard Triple Therapy for Helicobacter pylori Infection. Medicine (Baltimore) 2015; 94:e2104.
- 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.
- Gatta L, Vakil N, Vaira D, Scarpignato C. Global eradication rates for Helicobacter pylori infection: systematic review and meta-analysis of sequential therapy. BMJ 2013; 347:f4587.
- 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.
- 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.
- 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.
- 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.
- 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.
- Kale-Pradhan PB, Mihaescu A, Wilhelm SM. Fluoroquinolone Sequential Therapy for Helicobacter pylori: A Meta-analysis. Pharmacotherapy 2015; 35:719.
- 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.
- Vakil N. Primary and secondary treatment for Helicobacter pylori in the United States. Rev Gastroenterol Disord 2005; 5:67.
- 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.
- De Francesco V, Margiotta M, Zullo A, et al. Clarithromycin-resistant genotypes and eradication of Helicobacter pylori. Ann Intern Med 2006; 144:94.
- 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.
- Malfertheiner P, Leodolter A, Peitz U. Cure of Helicobacter pylori-associated ulcer disease through eradication. Baillieres Best Pract Res Clin Gastroenterol 2000; 14:119.
- Magaret N, Burm M, Faigel D, et al. A randomized trial of lansoprazole, amoxycillin, and clarithromycin versus lansoprazole, bismuth, metronidazole and tetracycline in the retreatment of patients failing initial Helicobacter pylori therapy. Dig Dis 2001; 19:174.
- 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.
- Cao Z, Chen Q, Zhang W, et al. Fourteen-day optimized levofloxacin-based therapy versus classical quadruple therapy for Helicobacter pylori treatment failures: a randomized clinical trial. Scand J Gastroenterol 2015; 50:1185.
- Gisbert JP, H. pylori Study Group of the Spanish Gastroenterology Association. Letter: third-line rescue therapy with levofloxacin after failure of two treatments to eradicate Helicobacter pylori infection. Aliment Pharmacol Ther 2012; 35:1484.
- 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.
- 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.
- Gisbert JP, Calvet X. Review article: rifabutin in the treatment of refractory Helicobacter pylori infection. Aliment Pharmacol Ther 2012; 35:209.
- 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.
- Yamato M, Watanabe T, Higuchi K, et al. Anti-inflammatory effects of pravastatin on Helicobacter pylori-induced gastritis in mice. Dig Dis Sci 2007; 52:2833.
- Liao WC, Huang MZ, Wang ML, et al. Statin Decreases Helicobacter pylori Burden in Macrophages by Promoting Autophagy. Front Cell Infect Microbiol 2016; 6:203.
- Murakami K, Sakurai Y, Shiino M, et al. 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.
- Sakurai K, Suda H, Ido Y, et al. Comparative study: Vonoprazan and proton pump inhibitors in Helicobacter pylori eradication therapy. World J Gastroenterol 2017; 23:668.
- Mahadevan U, Kane S. American gastroenterological association institute technical review on the use of gastrointestinal medications in pregnancy. Gastroenterology 2006; 131:283.
- Golberg D, Szilagyi A, Graves L. Hyperemesis gravidarum and Helicobacter pylori infection: a systematic review. Obstet Gynecol 2007; 110:695.
- Mansour GM, Nashaat EH. Role of Helicobacter pylori in the pathogenesis of hyperemesis gravidarum. Arch Gynecol Obstet 2011; 284:843.
- INDICATIONS FOR TREATMENT
- INITIAL ANTIBIOTIC THERAPY
- Approach to selecting an antibiotic regimen
- - Patients with risk factors for macrolide resistance
- - Patients without risk factors for macrolide resistance
- Duration of therapy
- Tolerability and compliance
- Antibiotic regimens
- - Bismuth quadruple therapy
- - Clarithromycin-based therapy
- Triple therapy
- Concomitant therapy
- Hybrid therapy
- Sequential therapy
- - Levofloxacin based therapy
- CONFIRMATION OF ERADICATION
- TREATMENT FAILURE
- Factors associated with antibiotic treatment failure
- Salvage therapy for persistent H. pylori infection
- - Suggested approach
- - Salvage regimens
- ADJUVANT THERAPIES WITH UNCLEAR ROLE
- TREATMENT DURING PREGNANCY AND LACTATION
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS