What is the best antibiotic regimen for treating gastritis caused by Helicobacter pylori (H. pylori)?

Best Antibiotic for H. pylori Gastritis

Bismuth quadruple therapy for 14 days is the best first-line antibiotic regimen for H. pylori gastritis, consisting of a PPI twice daily, bismuth 300mg four times daily, metronidazole 500mg three times daily, and tetracycline 500mg four times daily. 1

Why Bismuth Quadruple Therapy is Superior

• Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it the most reliable first-line option in the current era of widespread antibiotic resistance 2, 1
• Traditional clarithromycin-based triple therapy now fails in approximately 30% of cases due to clarithromycin resistance exceeding 15% in most regions of North America and Europe 2, 3
• No bacterial resistance to bismuth has been documented, and the synergistic effect of bismuth overcomes metronidazole resistance even when present in vitro 3
• Tetracycline resistance remains rare (<5%), making this combination effective regardless of prior antibiotic exposures 3

Specific Dosing Regimen

Standard bismuth quadruple therapy: 2, 1

• PPI (standard dose) twice daily: omeprazole 20mg, lansoprazole 30mg, pantoprazole 40mg, esomeprazole 20mg, or rabeprazole 20mg
• Bismuth subsalicylate 262mg or bismuth subcitrate 120mg four times daily
• Metronidazole 500mg three times daily (total 1.5g/day)
• Tetracycline 500mg four times daily
• Duration: 14 days (superior to 7-10 day regimens by approximately 5%) 2, 1

Critical Optimization Factors

• Take PPI 30 minutes before meals on an empty stomach without concurrent antacids to maximize acid suppression 2, 1
• Consider high-potency PPIs (esomeprazole 40mg or rabeprazole 40mg twice daily) to increase cure rates by 8-12% 3
• Counsel patients to avoid alcohol during metronidazole therapy due to disulfiram-like reactions 4

Second-Line Options After First-Line Failure

If bismuth quadruple therapy fails, use levofloxacin triple therapy: 2, 1

• PPI twice daily
• Amoxicillin 1000mg twice daily
• Levofloxacin 500mg once daily (or 250mg twice daily)
• Duration: 14 days

Critical caveat: Only use levofloxacin if the patient has no prior fluoroquinolone exposure for any indication, as resistance develops rapidly 2

Third-Line and Rescue Therapies

After two failed attempts, obtain antibiotic susceptibility testing before proceeding 2

If susceptibility testing is unavailable, consider: 2, 1

• Rifabutin triple therapy: rifabutin 150mg twice daily + amoxicillin 1000mg twice daily + PPI twice daily for 14 days
• High-dose dual therapy: amoxicillin 2-3g daily in 3-4 divided doses + high-dose PPI twice daily for 14 days

Alternative When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days: 2, 3

• PPI twice daily
• Amoxicillin 1000mg twice daily
• Clarithromycin 500mg twice daily
• Metronidazole 500mg twice daily

This regimen should only be used when bismuth is truly unavailable, as it exposes patients to clarithromycin (a "Watch" category antibiotic per WHO) and contributes to antimicrobial resistance 3

Special Populations

• Penicillin allergy: Bismuth quadruple therapy is ideal as it contains tetracycline instead of amoxicillin 1, 3
• Prior clarithromycin exposure: Never reuse clarithromycin—resistance is universal after macrolide exposure for any indication 2, 1
• Prior levofloxacin exposure: Never reuse fluoroquinolones—resistance develops rapidly 2, 1

Critical Antibiotic Reuse Rules

Can be reused: 1, 3

• Amoxicillin (resistance remains <5%)
• Tetracycline (resistance remains <5%)
• Metronidazole (when combined with bismuth, which overcomes resistance)

Never reuse: 2, 1

• Clarithromycin (resistance rates 10-34% primary, 15-67% secondary)
• Levofloxacin (resistance rates 11-30% primary, 19-30% secondary)

Verification of Eradication

• Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy 1, 3
• Stop PPIs at least 2 weeks before testing to avoid false-negative results 1, 3
• Never use serology to confirm eradication—antibodies persist long after successful treatment 3

Common Pitfalls to Avoid

• Do not use standard clarithromycin triple therapy as first-line treatment—it now achieves only 70% eradication rates in most regions due to resistance 2, 5, 6
• Do not use 7-day regimens—14 days improves success by approximately 5% 2, 1
• Do not use once-daily PPI dosing—twice-daily dosing is mandatory for optimal acid suppression 1, 3
• Do not assume low clarithromycin resistance without local surveillance data—most regions now exceed 15% resistance 3
• Do not prescribe levofloxacin as first-line therapy—reserve it for second-line use only 2

Why Not Other Regimens?

• Clarithromycin triple therapy: Fails in 30% of cases due to resistance exceeding 15% in most regions 2, 3, 5
• Sequential therapy: No advantage over concomitant therapy and adds unnecessary complexity 6
• Probiotics: Unproven benefit for eradication; may reduce side effects but should be considered experimental 2, 3

2, 1, 3, 4, 7, 5, 8, 6, 9, 10