What is the recommended antibiotic regimen for Helicobacter pylori (H. pylori)-related gastritis?

Antibiotic Treatment for H. pylori-Related Gastritis

For H. pylori-related gastritis, use bismuth quadruple therapy for 14 days as first-line treatment: bismuth ~300mg four times daily, metronidazole 500mg three times daily, tetracycline 500mg four times daily, and a PPI twice daily. 1, 2

First-Line Treatment Selection

The choice of first-line regimen depends critically on local clarithromycin resistance patterns:

In Areas with High Clarithromycin Resistance (>15-20%)

• Bismuth quadruple therapy is the preferred regimen consisting of bismuth ~300mg four times daily, metronidazole 500mg three times daily, tetracycline 500mg four times daily, and PPI twice daily for 14 days 1
• This regimen achieves eradication rates of 80-90% even in the presence of metronidazole resistance 1, 2
• Clarithromycin-containing triple therapy should be abandoned when local resistance exceeds 15-20% due to unacceptably low cure rates 1, 2

Alternative First-Line Option (When Bismuth Unavailable)

• Concomitant non-bismuth quadruple therapy can be used: PPI twice daily, amoxicillin 1000mg twice daily, metronidazole 500mg twice daily, and clarithromycin 500mg twice daily for 14 days 1
• This is appropriate only in areas of high clarithromycin resistance where bismuth is not available 1

In Areas with Low Clarithromycin Resistance (<15%)

• Clarithromycin triple therapy may be considered: PPI twice daily, clarithromycin 500mg twice daily, and amoxicillin 1000mg twice daily (or metronidazole 500mg twice daily) for 14 days 1
• However, bismuth quadruple therapy remains an excellent alternative even in low-resistance areas 1

Critical Treatment Optimization

PPI Dosing

• Always use high-dose PPI (twice daily) rather than standard dosing 1, 2
• High-dose PPI increases eradication efficacy by 6-10% compared to standard doses 1, 2
• Standard doses: pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, dexlansoprazole 30mg, rabeprazole 20mg 1
• Administer PPI 30 minutes before eating on an empty stomach without concomitant antacids 1

Treatment Duration

• 14 days is the recommended duration for all first-line regimens 1, 2
• Extending from 7 to 14 days improves eradication success by approximately 5% 1, 2
• Some guidelines accept 10-14 days for bismuth quadruple therapy if 10 days has been proven locally effective 1

Second-Line Treatment After First-Line Failure

After Clarithromycin-Based Therapy Fails

• Switch to bismuth quadruple therapy (if not used initially): bismuth ~300mg four times daily, metronidazole 500mg three times daily, tetracycline 500mg four times daily, PPI twice daily for 14 days 1

After Bismuth Quadruple Therapy Fails

• Assess for true penicillin allergy before proceeding 1
• If no penicillin allergy and levofloxacin resistance is unknown or low:
  • Levofloxacin triple therapy: levofloxacin 500mg once daily, amoxicillin 1000mg twice daily, PPI twice daily for 14 days 1
• Avoid levofloxacin if resistance is known or suspected due to rising resistance rates 1

After Two Failed Attempts

• Obtain antimicrobial susceptibility testing before any further treatment 1
• Options after susceptibility testing include rifabutin triple therapy, high-dose dual therapy, or levofloxacin quadruple therapy based on resistance patterns 1
• Rifabutin triple therapy: rifabutin 150-300mg daily, amoxicillin 1000mg twice daily, PPI twice daily for 10 days 1

Verification of Eradication

• Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy 1, 2
• Testing must be done at least 2 weeks after PPI discontinuation 2
• Never use serology to confirm eradication as antibodies persist long after successful treatment 1, 2

Common Pitfalls and Caveats

Antibiotic Resistance

• Clarithromycin resistance is the primary cause of triple therapy failure, with global rates increasing from 9% in 1998 to 17.6% in 2008-2009 2
• Rising levofloxacin resistance rates must be considered when selecting second-line therapy 1
• Rifabutin and amoxicillin resistance remain rare, making rifabutin triple therapy reasonable without prior susceptibility testing 1

Patient Factors

• Smoking significantly reduces eradication success with clarithromycin-based regimens 3
• Patients with mild gastritis have lower eradication rates compared to those with severe inflammation 3
• Patient adherence is critical—confirm compliance before declaring treatment failure 1

Medication Administration

• Inadequate PPI dosing is a major cause of treatment failure 2
• Do not use concomitant H2-receptor antagonists with PPIs as this reduces efficacy 1
• Probiotics may reduce side effects but are of unproven benefit for improving eradication rates 1