What are the guidelines for treating Helicobacter pylori (H. pylori) infection?

H. pylori Treatment Guidelines

First-Line Treatment: Bismuth Quadruple Therapy is Preferred

Bismuth quadruple therapy (BQT) for 14 days is the recommended first-line treatment for H. pylori infection in most clinical scenarios, consisting of a PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

Why Bismuth Quadruple Therapy is Superior

• Bacterial resistance to bismuth is extremely rare, making BQT effective even against metronidazole-resistant strains, with eradication rates consistently exceeding 80-90% 1, 2
• Clarithromycin resistance now exceeds 15% in most regions of North America, rendering traditional triple therapy unacceptably ineffective with failure rates over 20% 1, 3
• The World Health Organization has identified H. pylori as one of only 12 bacterial species requiring urgent investment in new antibiotics due to high clarithromycin resistance rates 1

Specific Dosing for Bismuth Quadruple Therapy

• PPI (standard dose) twice daily
• Bismuth subsalicylate 525 mg four times daily
• Metronidazole 500 mg three to four times daily (higher doses of 1.5-2 g daily in divided doses improve eradication rates even with resistant strains) 1
• Tetracycline 500 mg four times daily
• Duration: 14 days is strongly preferred over 10 days to maximize eradication rates 1, 2

Alternative First-Line Regimens When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth is not available, consisting of PPI twice daily, amoxicillin 1000 mg twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg twice daily 1, 2

When Triple Therapy May Still Be Considered

• Only in areas with documented clarithromycin resistance below 15% should triple therapy (PPI + clarithromycin 500 mg + amoxicillin 1000 mg, all twice daily for 14 days) be considered 1, 2
• Standard triple therapy should be completely abandoned when regional clarithromycin resistance exceeds 15-20% 1, 2

Rifabutin Triple Therapy as an Alternative

• For patients without penicillin allergy, rifabutin triple therapy (rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily) for 14 days is an acceptable first-line alternative 1, 3
• Resistance to rifabutin and amoxicillin remains extremely rare (1-5%) 1

Optimizing Treatment Success

Critical Treatment Principles

• High-dose PPI twice daily is essential to reduce gastric acidity and enhance antibiotic activity 1, 2
• 14-day treatment duration improves eradication success by approximately 5% compared to 7-day regimens 1, 2
• Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance 4

Managing Side Effects

• Diarrhea occurs in 21-41% of patients during the first week due to disruption of normal gut microbiota 1
• Consider adjunctive probiotics to reduce diarrhea risk and improve patient compliance 1, 2

Second-Line Treatment After First-Line Failure

After failed first-line therapy, select an alternative regimen based on prior antibiotic exposure—never repeat antibiotics the patient has already received, especially clarithromycin and levofloxacin. 1, 2

Recommended Second-Line Options

• If BQT was not used initially, use optimized BQT for 14 days 2, 3
• Levofloxacin-based triple therapy (PPI + amoxicillin 1000 mg + levofloxacin 500 mg, all twice daily for 14 days) only in areas with low levofloxacin resistance and if not previously used 1, 2
• Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates and FDA warnings about serious side effects 1

Third-Line and Rescue Therapies

After two failed eradication attempts, antibiotic susceptibility testing is strongly recommended to guide further treatment. 1, 2

Rescue Options When Susceptibility Testing is Unavailable

• Rifabutin-based triple therapy (rifabutin 150 mg + amoxicillin 1000 mg + PPI, all twice daily for 14 days) is highly effective as rescue therapy 1, 3
• High-dose dual therapy with amoxicillin (1000 mg three times daily) and PPI (high-dose twice daily) for 14 days 1, 4
• Use antibiotics not previously used or for which resistance is unlikely: amoxicillin, tetracycline, bismuth, or furazolidone 5

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy and at least 2 weeks after PPI discontinuation. 1, 2

• Do not use serology for post-treatment confirmation 2
• Universal test-of-cure is recommended for all patients 3

Critical Pitfalls to Avoid

Antibiotic Selection Errors

• Never repeat clarithromycin or levofloxacin if previously used—resistance is highly likely to have developed 1, 2
• Avoid concomitant, sequential, or hybrid therapies as they include unnecessary antibiotics that contribute to global antibiotic resistance 1
• Do not assume penicillin allergy without verification—consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 1

Treatment Duration Mistakes

• Never use 7-day regimens when 14-day regimens are feasible—the additional week significantly improves eradication rates 1, 2
• Continue treatment for the full duration even if symptoms resolve early 4

Dosing Adjustments for Renal Impairment

• Patients with GFR less than 30 mL/min should NOT receive the 875 mg amoxicillin dose 4
• For GFR 10-30 mL/min: amoxicillin 500 mg or 250 mg every 12 hours 4
• For GFR less than 10 mL/min: amoxicillin 500 mg or 250 mg every 24 hours 4