What is the recommended treatment for a patient with Helicobacter pylori (H. pylori) positive gastritis?

Treatment of Helicobacter Pylori Positive Gastritis

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori positive gastritis, consisting of a high-dose PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1

First-Line Treatment Regimen

Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it superior to traditional triple therapy. 1 This regimen should include:

• Esomeprazole or rabeprazole 40 mg twice daily (preferred over other PPIs as they increase cure rates by 8-12%) 1
• Bismuth subsalicylate 262 mg (2 tablets) four times daily 1
• Metronidazole 500 mg three to four times daily (total 1.5-2 g daily) 1
• Tetracycline 500 mg four times daily 1
• Duration: 14 days (mandatory, as this improves eradication by approximately 5% compared to 7-10 day regimens) 1

The PPI should be taken 30 minutes before meals on an empty stomach, without concomitant use of other antacids. 1

Why Bismuth Quadruple Therapy is Preferred

The superiority of this regimen is based on several critical factors:

• No bacterial resistance to bismuth has been described 1
• Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, making traditional triple therapy achieve only 70% eradication rates 1
• Bismuth's synergistic effect overcomes metronidazole resistance, even when in vitro resistance exists 1
• Tetracycline and amoxicillin resistance remains rare (<5%) 1

Alternative First-Line Option When Bismuth is Unavailable

If bismuth is not available, concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative: 1

• PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
• Amoxicillin 1000 mg twice daily 1
• Clarithromycin 500 mg twice daily 1
• Metronidazole 500 mg twice daily 1

This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing the development of resistance during treatment. 1

Second-Line Treatment After First-Line Failure

Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 1 After first-line failure:

• If bismuth quadruple therapy was not used first-line, use it as second-line for 14 days 1
• If bismuth quadruple therapy failed, use levofloxacin triple therapy (only if no prior fluoroquinolone exposure): 1
  • Esomeprazole or rabeprazole 40 mg twice daily
  • Amoxicillin 1000 mg twice daily
  • Levofloxacin 500 mg once daily
  • Duration: 14 days

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1 Options include:

• Rifabutin triple therapy for 14 days: 1

  • Rifabutin 150 mg twice daily
  • Amoxicillin 1000 mg twice daily
  • High-dose PPI twice daily

• High-dose dual amoxicillin-PPI therapy for 14 days: 1

  • Amoxicillin 2-3 grams daily in 3-4 split doses
  • High-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily

Confirmation of Eradication

Mandatory verification of H. pylori eradication is required at least 4 weeks after completing therapy. 1 Use:

• Urea breath test (13C-UBT) as the gold standard 2
• Monoclonal stool antigen test as an equivalent alternative 2
• Discontinue PPIs at least 2 weeks before testing 1
• Never use serology to confirm eradication, as antibodies persist long after successful treatment 1

Critical Pitfalls to Avoid

• Do not use standard triple therapy (PPI + clarithromycin + amoxicillin) as first-line treatment in most regions, as clarithromycin resistance exceeds 15% 1
• Do not use standard-dose PPI once daily—always use high-dose twice-daily dosing 1
• Do not use 7-day regimens—14 days is mandatory for optimal outcomes 1
• Do not use levofloxacin as first-line therapy, as this accelerates resistance development 1
• Do not assume penicillin allergy without verification—consider penicillin allergy testing to enable amoxicillin use 1
• Avoid concomitant, sequential, or hybrid therapies, as they include unnecessary antibiotics that contribute to global antibiotic resistance 1

Special Clinical Considerations

In patients with penicillin allergy, bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin. 1

Patient compliance is critical, as more than 10% of patients have poor adherence, drastically reducing eradication rates. 3 Address this by:

• Explaining the importance of completing the full 14-day course 1
• Warning about potential side effects (diarrhea occurs in 21-41% during the first week) 1
• Considering adjunctive probiotics to reduce diarrhea and improve compliance 1

Why H. pylori Eradication Matters for Gastritis

H. pylori eradication is strongly recommended in all infected patients with gastritis, as it results in cure in over 90% of patients and prevents progression to more serious conditions. 4 Specific indications include:

• All patients with gastric ulcer 4
• Patients receiving long-term anti-secretory maintenance treatment 4
• Patients with advanced and progressively worsening forms of gastritis, such as intestinal metaplasia 4
• Patients with a family history of gastric cancer 4

H. pylori eradication heals gastritis and prevents progression to atrophic gastritis, though evidence for reducing gastric cancer risk is limited once preneoplastic changes have occurred. 1