Helicobacter pylori infection medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: ;Yamuna Kondapally, M.B.B.S[2]

Overview

Indications for treatment of H. pylori infection include past or present duodenal and/or gastric ulcer, with or without complications, following resection of gastric cancer, gastric mucosa-associated lymphoid tissue (MALT) lymphoma, atrophic gastritis, dyspepsia, patients with first-degree relatives with gastric cancer and patient‘s wishes. Factors involved in choosing treatment regimens include prevalence of H. pylori infection, prevalence of gastric cancer, resistance to antibiotics, availability of bismuth, availability of endoscopy and H. pylori tests, ethnicity, drug allergies and tolerance, previous treatments and outcome, adverse effects, effectiveness of local treatment and recommended dosages and treatment duration.

Medical Therapy

Indications for treatment of H. pylori infection include:[1]

Factors involved in choosing treatment regimens include:[1]

  • Prevalence of H. pylori infection
  • Prevalence of gastric cancer
  • Resistance to antibiotics
  • Availability of bismuth
  • Cost of tests
  • Availability of endoscopy and H. pylori tests
  • Ethnicity
  • Drug allergies and tolerance
  • Previous treatments and outcome
  • Ease of administration
  • Adverse effects
  • Effectiveness of local treatment
  • Recommended dosages and treatment duration

First-Line Regimens for Helicobacter pylori Eradication

Regimen Duration Eradication rates Comments
Standard dose PPI b.i.d. (esomeprazole is q.d.),

clarithromycin 500 mg b.i.d., amoxicillin 1,000 mg b.i.d.

10–14 70–85% Consider in nonpenicillin allergic patients who have not previously received a macrolide
Standard dose PPI b.i.d., clarithromycin 500 mg b.i.d.

metronidazole 500 mg b.i.d.

10–14 70–85% Consider in penicillin allergic patients who have not previously received a macrolide or are unable to tolerate bismuth quadruple therapy
Bismuth subsalicylate 525 mg p.o. q.i.d. metronidazole

250 mg p.o. q.i.d., tetracycline 500 mg p.o. q.i.d.,

ranitidine 150 mg p.o. b.i.d. or standard dose

PPI q.d. to b.i.d.

10–14 75–90% Consider in penicillin allergic patients
PPI + amoxicillin 1 g b.i.d. followed by

PPI, clarithromycin 500 mg, tinidazole 500 mg b.i.d.

5

5

>90% Requires validation in North America
PPI = proton pump inhibitor; pcn = penicillin; p.o. = orally; q.d. = daily; b.i.d. = twice daily; t.i.d. = three times daily; q.i.d. = four times daily.

*Standard dosages for PPIs are as follows:

lansoprazole 30 mg p.o., omeprazole 20 mg p.o., pantoprazole 40 mg p.o., rabeprazole 20 mg p.o., esomeprazole 40 mg p.o.

Note: the above-recommended treatments are not all FDA approved.

FDA approved regimens are as follows:

1. Bismuth 525 mg q.i.d. + metronidazole 250 mg q.i.d. + tetracycline 500 mg q.i.d. × 2 wk + H2RA as directed × 4 wk.

2. Lansoprazole 30 mg b.i.d. + clarithromycin 500 mg b.i.d. + amoxicillin 1 g b.i.d. × 10 days.

3. Omeprazole 20 mg b.i.d. + clarithromycin 500 mg b.i.d. + amoxicillin 1 g b.i.d. × 10 days.

4. esomeprazole 40 mg q.d. + clarithromycin 500 mg b.i.d. + amoxicillin 1 g b.i.d. × 10 days.

5. Rabeprazole 20 mg b.i.d. + clarithromycin 500 mg b.i.d. + amoxicillin 1 g b.i.d. × 7 days.

Predictors of H.pylori Treatment Outcome

Predictors of treatment failure include:

  • Poor compliance
  • Antibiotic resistance (key factor in the failure of eradication therapy and recurrence of H. pylori infection)
  • Bacterial factors like CagA-negative strains are at increased risk of treatment failure compared with CagA-positive strains
  • CYP2C 19 polymorphisms may influence treatment outcomes when regimens containing PPIs are used as they influence the clearance of PPIs and thus their effect on gastric acid secretion.
Drugs Side effects Recommendations
Proton pump inhibitors (PPIs) PPIs should be taken 30-60 min before eating to optimize their effects on gastric acid secretion.
Clarithromycin
  • GI upset
  • Headache
  • Altered taste
Amoxicillin
Metronidazole
  • Metallic taste in the mouth
  • Dyspepsia
  • A disulfiram-like reaction with alcohol consumption
Tetracycline Tetracyclinhes should not be given to children under 8 yr of age because of possible tooth discoloration
Bismuth Compounds
  • Darkening of tongue and stool
  • Nausea
  • GI upset

Salvage Therapy for Persistent H.pylori Infection

  • In patients with persistent H. pylori infection, every effort should be made to avoid antibiotics that have been previously taken by the patient.[2]
  • Bismuth-based quadruple therapy for 7-14 days is an accepted salvage therapy.
  • Levofloxacin-based triple therapy for 10 days is another option in patients with persistent infection, which requires validation in the United States.
Regimen Duration Eradication rates Comments
Bismuth quadruple therapy

PPI q.d. tetracycline, Pepto Bismol, metronidazole q.i.d.

7 68% Accessible, cheap but high pill count, and frequent mild side effects
Levofloxacin triple therapy

PPI, amoxicillin 1 g b.i.d., levofloxacin 500 mg q.d.

10 10 87% Requires validation in North America
  • Triple therapy should be used if a patient has persistent infection who has previously not been treated with clarithromycin.
  • In patients who were treated with clarithromycin initially, bismuth quadruple therapy is used as salvage therapy.

Other Alternative Antibiotics

Rifabutin

Furazolindone

Levofloxacin

H.pylori Treatment Options in Developing Countries

H. pylori treatment options in developing countries include:[1]

First-Line therapies
PPI + amoxicillin + clarithromycin

(All twice daily for 7 days)

  • Used and accepted throughout the world
  • Eradication rates have fallen to 70-85% over the last few years, in part due to increasing resistance to clarithromycin
  • Cost considerations and compliance issues may favor 7-days therapy
  • Some groups suggest treatment for 10 or 14 days
  • Other inexpensive macrolides, such as azithromycin, are available over the counter in developing countries, and macrolide cross-resistance affects eradication rate
In case of a clarithromycin resistance rate of more than 20%:

Quadruple therapy: PPI b.i.d. + bismuth + tetracycline + metronidazole all q.i.d. for 7 - 10 days

  • May be cheaper than triple therapy
  • More difficult to take than triple therapy. A single triple capsule has been shown to facilitate its use
  • Equivalent eradication rates in comparison with standard triple therapy
  • In vitro metronidazole resistance may be overcome by prolonging therapy or using high doses of metronidazole
If there is no known clarithromycin resistance or clarithromycin resistance is not likely:
  • PPI + amoxicillin + clarithromycin for 7 days
  • Quadruple therapy: PPI + bismuth + tetracycline + metronidazole for 7-10 days
  • If bismuth not available: concomitant therapy: PPI + clarithromycin + metronidazole + amoxicillin for 14 days
  • Furazolidone-containing regimens: PPI + furazolidone + antibiotic is slightly less effective than the standard triple regimens
  • Furazolidone can replace amoxicillin in standard triple therapy
  • Sequential regimen: 10-day therapy with PPI + amoxicillin for 5 days followed by PPI + clarithromycin and a nitroimidazole (tinidazole) for 5 days
B Second-line therapies, after failure of clarithromycin incontaining regimens
  • PPI + bismuth + tetracycline + metronidazole for 10-14 days
  • PPI + amoxicillin + levofloxacin for 10 days
  • PPI + furazolidone + tetracycline + bismuth for 10 days
  • PPI + furazolidone + levofloxacine for 10 days
  • PPI + amoxicillin + clarithromycin for 7 days
  • PPI + amoxicillin + levofloxacin for 10 days
  • PPI + furazolidone + levofloxacin for 10 days
C Third-line therapies, after failure of clarithromycin-containing regimens and quadruple therapy
  • PPI + amoxicillin + levofloxacin for 10 days
  • PPI + amoxicillin + rifabutin for 10 days
  • PPI + furazolidone + levofloxacin for 7-10 days

B.i.d (twice a day); q.i.d (four times a day); PPI, proton-pump inhibitor

Testing to Prove Eradication After Antibiotic Therapy

The following are the indications for testing to prove eradication after antibiotic therapy.[13]

  • Any patient with an H.pylori-associated ulcer.
  • Individuals with persistent dyspeptic symptoms despite the test-and-treat strategy.
  • Those with H.pylori associated MALT lymphoma.
  • Individuals who have undergone resection of early gastric cancer.

References

  1. 1.0 1.1 1.2 Hunt RH, Xiao SD, Megraud F, Leon-Barua R, Bazzoli F, van der Merwe S; et al. (2011). "Helicobacter pylori in developing countries. World Gastroenterology Organisation Global Guideline". J Gastrointestin Liver Dis. 20 (3): 299–304. PMID 21961099.
  2. 2.0 2.1 Isakov V, Domareva I, Koudryavtseva L, Maev I, Ganskaya Z (2002). "Furazolidone-based triple 'rescue therapy' vs. quadruple 'rescue therapy' for the eradication of Helicobacter pylori resistant to metronidazole". Aliment Pharmacol Ther. 16 (7): 1277–82. PMID 12144577.
  3. Miehlke S, Hansky K, Schneider-Brachert W, Kirsch C, Morgner A, Madisch A; et al. (2006). "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. 24 (2): 395–403. doi:10.1111/j.1365-2036.2006.02993.x. PMID 16842467.
  4. Perri F, Festa V, Clemente R, Villani MR, Quitadamo M, Caruso N; et al. (2001). "Randomized study of two "rescue" therapies for Helicobacter pylori-infected patients after failure of standard triple therapies". Am J Gastroenterol. 96 (1): 58–62. doi:10.1111/j.1572-0241.2001.03452.x. PMID 11197288.
  5. Bock H, Koop H, Lehn N, Heep M (2000). "Rifabutin-based triple therapy after failure of Helicobacter pylori eradication treatment: preliminary experience". J Clin Gastroenterol. 31 (3): 222–5. PMID 11034001.
  6. Wong WM, Gu Q, Lam SK, Fung FM, Lai KC, Hu WH; et al. (2003). "Randomized controlled study of rabeprazole, levofloxacin and rifabutin triple therapy vs. quadruple therapy as second-line treatment for Helicobacter pylori infection". Aliment Pharmacol Ther. 17 (4): 553–60. PMID 12622764.
  7. Borody TJ, Pang G, Wettstein AR, Clancy R, Herdman K, Surace R; et al. (2006). "Efficacy and safety of rifabutin-containing 'rescue therapy' for resistant Helicobacter pylori infection". Aliment Pharmacol Ther. 23 (4): 481–8. doi:10.1111/j.1365-2036.2006.02793.x. PMID 16441468.
  8. Ali BH (1999). "Pharmacological, therapeutic and toxicological properties of furazolidone: some recent research". Vet Res Commun. 23 (6): 343–60. PMID 10543364.
  9. Wong WM, Wong BC, Lu H, Gu Q, Yin Y, Wang WH; et al. (2002). "One-week omeprazole, furazolidone and amoxicillin rescue therapy after failure of Helicobacter pylori eradication with standard triple therapies". Aliment Pharmacol Ther. 16 (4): 793–8. PMID 11929398.
  10. Saad RJ, Schoenfeld P, Kim HM, Chey WD (2006). "Levofloxacin-based triple therapy versus bismuth-based quadruple therapy for persistent Helicobacter pylori infection: a meta-analysis". Am J Gastroenterol. 101 (3): 488–96. doi:10.1111/j.1572-0241.1998.455_t.x. PMID 16542284.
  11. Gisbert JP, Morena F (2006). "Systematic review and meta-analysis: levofloxacin-based rescue regimens after Helicobacter pylori treatment failure". Aliment Pharmacol Ther. 23 (1): 35–44. doi:10.1111/j.1365-2036.2006.02737.x. PMID 16393278.
  12. Gisbert JP, Castro-Fernández M, Bermejo F, Pérez-Aisa A, Ducons J, Fernández-Bermejo M; et al. (2006). "Third-line rescue therapy with levofloxacin after two H. pylori treatment failures". Am J Gastroenterol. 101 (2): 243–7. doi:10.1111/j.1572-0241.2006.00457.x. PMID 16454825.
  13. Laine L, Sugg J, Suchower L, Neil G (2000). "Endoscopic biopsy requirements for post-treatment diagnosis of Helicobacter pylori". Gastrointest Endosc. 51 (6): 664–9. PMID 10840297.

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