What are the treatment guidelines for Helicobacter pylori (H. pylori) gastritis?

Treatment Guidelines for H. pylori Gastritis

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori gastritis, consisting of a high-dose PPI twice daily, bismuth subsalicylate (524 mg four times daily), metronidazole (500 mg three to four times daily), and tetracycline (500 mg four times daily). 1, 2

First-Line Treatment Selection

The choice of first-line therapy depends critically on local clarithromycin resistance patterns, though bismuth quadruple therapy is now preferred in most settings:

Bismuth Quadruple Therapy (Preferred)

• This regimen achieves 80-90% eradication rates even against metronidazole-resistant strains due to bismuth's synergistic effect with other antibiotics. 1
• Bacterial resistance to bismuth is extremely rare, and tetracycline resistance remains uncommon. 1, 2
• The regimen consists of:
  • PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
  • Bismuth subsalicylate 524 mg four times daily 2
  • 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 is mandatory (not 10 days) 1, 2

Alternative: Concomitant Non-Bismuth Quadruple Therapy

• Use only when bismuth is unavailable. 1
• Regimen: PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days. 1
• This avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing resistance development during treatment. 1

Clarithromycin-Based Triple Therapy (Rarely Appropriate)

• Standard triple therapy should be abandoned when regional clarithromycin resistance exceeds 15-20%, which now includes most of North America and Central, Western, and Southern Europe. 1
• When clarithromycin-resistant strains are present, eradication rates drop from 90% to approximately 20%. 1
• Only consider in areas with documented low clarithromycin resistance (<15%): PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily for 14 days. 1, 3, 4

Critical Optimization Factors

PPI Selection and Dosing

• Use high-potency PPIs at high doses: esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8-12%. 5, 1
• Avoid pantoprazole (40 mg pantoprazole = only 9 mg omeprazole equivalent). 5
• Take PPI 30 minutes before meals on an empty stomach. 1
• Standard once-daily PPI dosing is inadequate and should never be used. 1

Treatment Duration

• 14 days is superior to 7-10 day regimens, improving eradication by approximately 5%. 1, 6
• This is non-negotiable for maximizing first-attempt success. 1

Patient Factors Affecting Success

• Smoking increases eradication failure risk (odds ratio 1.95). 1
• High BMI/obesity reduces drug concentrations at the gastric mucosal level. 1
• Poor compliance (>10% of patients) dramatically reduces eradication rates—address this proactively. 1

Second-Line Treatment After First Failure

Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 1, 2

Preferred Second-Line Options

• Bismuth quadruple therapy for 14 days (if not used first-line). 1
• Levofloxacin triple therapy: PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) for 14 days. 1
  • Use only in areas with low levofloxacin resistance and if not previously exposed. 1
  • Rising levofloxacin resistance rates (11-30% primary, 19-30% secondary) limit this option. 1

Third-Line and Rescue Therapies

After Two Failed Attempts

• Antibiotic susceptibility testing should guide further treatment whenever possible. 1, 6
• Molecular testing for clarithromycin and levofloxacin resistance can guide earlier therapy selection. 1

Rescue Regimen Options

• Rifabutin triple therapy: Rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily for 14 days. 1
  • Rifabutin resistance is extremely rare. 1
  • Reserve for patients who have failed multiple prior attempts. 1
• High-dose dual therapy: Amoxicillin 2-3 grams daily in 3-4 divided doses + high-dose PPI twice daily for 14 days. 1
  • Use only when other options are exhausted. 1

Special Populations

Penicillin Allergy

• Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin. 1
• Verify penicillin allergy—consider allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare. 1

Pediatric Patients

• Treatment should only be conducted by pediatric gastroenterologists in specialist centers. 1
• First-line options: PPI + amoxicillin + clarithromycin, PPI + amoxicillin + metronidazole, or bismuth + amoxicillin + metronidazole. 1

Confirmation of Eradication

• Test at least 4 weeks after completion of therapy using urea breath test or validated monoclonal stool antigen test. 1
• Discontinue PPI at least 2 weeks before testing. 1
• Never use serology to confirm eradication—antibodies persist long after successful treatment. 1

Adjunctive Therapy

• Consider probiotics to reduce antibiotic-associated diarrhea (occurs in 21-41% of patients) and improve compliance. 1, 6
• Evidence for probiotics improving eradication rates is limited, but they reduce side effects. 1, 6

Critical Pitfalls to Avoid

• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates. 1
• Avoid repeating clarithromycin if the patient has any prior macrolide exposure (for any indication), as cross-resistance is universal. 1
• Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates. 1
• Never use concomitant, sequential, or hybrid therapies as they include unnecessary antibiotics that contribute to global antibiotic resistance. 1
• Metronidazole can be re-used with bismuth because bismuth's synergistic effect overcomes in vitro resistance. 1
• Amoxicillin and tetracycline can be re-used because resistance to these agents remains rare. 1

Antimicrobial Stewardship Considerations

• Bismuth quadruple therapy uses antibiotics from the WHO "Access group" (tetracycline and metronidazole) rather than the "Watch group" (clarithromycin, levofloxacin), making it preferable from an antimicrobial stewardship perspective. 1
• The FDA recommends fluoroquinolones be used as a last choice due to risk of serious side effects. 1

Paradigm Shift in H. pylori Management

• H. pylori gastritis should be treated as an infectious disease with the goal of near-100% cure rates, not as a typical gastroenterological disease with modest success rates. 5
• The primary outcome variable is actual cure rate, with the comparator being the theoretical 100% cure rate, not comparison to other marginally effective therapies. 5
• Future treatment trials will focus on actual cure rates ≥90%, preferably ≥95%, requiring abandonment of prior approaches based on comparisons of poorly effective therapies. 5