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:

• 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
• Patients wishes

Factors involved in choosing treatment regimens include:

• 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

• Bismuth quadruple therapy has been advocated as a primary therapy for H. pylori.
• In patients who have not previously received clarithromycin and who are not allergic to penicillin, PPI, clarithromycin, and amoxicillin are considered.
• For patients allergic to penicillin, metronidazole is given as an alternative for amoxicillin.
• In patients who are allergic to penicillin or those who have previously been treated with a macrolide antibiotic, bismuth quadraple therapy is considered.

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)	Headache Diarrhea	PPIs should be taken 30-60 min before eating to optimize their effects on gastric acid secretion.
Clarithromycin	GI upset Headache Altered taste
Amoxicillin	GI upset Headache Diarrhea
Metronidazole	Metallic taste in the mouth Dyspepsia A disulfiram-like reaction with alcohol consumption
Tetracycline	GI upset Photosensitivity	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.
• 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

• Rifabutin is used as an alternate antibiotic in patients with clarithromycin or metronidazole resistance.
• Side effects include rash, nausea, vomiting, dyspepsia, diarrhea, myelotoxicity and ocular toxicity

Furazolindone

• Furazolidone is used as an alternative to clarithromycin, metronidazole, or amoxicillin
• Not currently used in the United states
• Side effects include nausea, vomiting, headache and malaise

Levofloxacin

• Levofloxacin-based triple therapy (PPI, levofloxacin, and amoxicillin) can be used as second and third-line therapy in patients with persistent H. pylori infection.

H.pylori Treatment Options in Developing Countries

H. pylori treatment options in developing countries include:

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.

• 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.