What is the first line treatment regimen for H. pylori (Helicobacter pylori) gastritis?

First-Line Treatment for H. pylori Gastritis

Bismuth quadruple therapy for 14 days is the most up-to-date first-line treatment for H. pylori gastritis, consisting of a PPI twice daily, bismuth subsalicylate (262 mg four times daily), metronidazole (500 mg three to four times daily), and tetracycline (500 mg four times daily). 1, 2, 3

Why Bismuth Quadruple Therapy is Now First-Line

The paradigm has shifted away from clarithromycin-based triple therapy because:

• Clarithromycin resistance now exceeds 15% in most regions of North America and Europe, making traditional triple therapy achieve only 70% eradication rates—well below the 80% minimum target 1, 2
• When H. pylori strains are clarithromycin-resistant, eradication rates drop from 90% to approximately 20% 2
• The WHO has identified H. pylori as one of only 12 bacterial species requiring urgent investment in new antibiotics due to high clarithromycin resistance 2

Bismuth quadruple therapy achieves 80-90% eradication rates even against metronidazole-resistant strains due to bismuth's synergistic effect with other antibiotics 1, 2, 3

The Complete First-Line Regimen

Standard Dosing:

• PPI twice daily (taken 30 minutes before meals on an empty stomach): pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, dexlansoprazole 30mg, or rabeprazole 20mg 3
• Bismuth subsalicylate 262 mg (2 tablets) four times daily or bismuth subcitrate 120 mg four times daily 2, 3
• Metronidazole 500 mg three to four times daily (total 1.5-2 g daily) 1, 2, 3
• Tetracycline 500 mg four times daily 1, 2, 3

Critical Optimization Factors:

High-dose PPI twice daily is mandatory—standard once-daily dosing is inadequate and reduces cure rates by 6-10% 4, 1. Using esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by an additional 8-12% compared to other PPIs 4, 1, 2

14-day duration is superior to 7-10 day regimens, improving eradication success by approximately 5% 4, 1, 2

Alternative First-Line Option When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days is the preferred alternative: 1, 2

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

This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing resistance development during treatment 4, 1

When Clarithromycin-Based Triple Therapy Can Still Be Used

Only in areas with documented clarithromycin resistance <15% can triple therapy (PPI + clarithromycin 500mg twice daily + amoxicillin 1000mg twice daily for 14 days) be considered 1, 2. However, most regions now exceed this threshold 2

Second-Line Treatment After First-Line Failure

If Bismuth Quadruple Therapy Fails:

Levofloxacin triple therapy for 14 days (if no prior fluoroquinolone exposure): 4, 1, 3

• PPI twice daily
• Amoxicillin 1000 mg twice daily
• Levofloxacin 500 mg once daily (or 250 mg twice daily)

Critical caveat: Levofloxacin should not be used empirically without susceptibility testing when population resistance rates exceed 15%, as rising fluoroquinolone resistance (11-30% primary, 19-30% secondary) significantly reduces efficacy 4, 1, 2

If Clarithromycin-Based Therapy Fails:

Use bismuth quadruple therapy as described above 1, 3

Third-Line and Rescue Therapies

After two failed eradication attempts, antibiotic susceptibility testing should guide further treatment whenever possible 4, 1

Rifabutin Triple Therapy (14 days):

• Rifabutin 150 mg twice daily (or 300 mg once daily)
• Amoxicillin 1000 mg twice daily
• PPI twice daily

Rifabutin resistance is rare, making this highly effective as rescue therapy 4, 1, 2, 3

High-Dose Dual Therapy (14 days):

• Amoxicillin 2-3 grams daily in 3-4 split doses
• High-dose PPI twice daily

This is an alternative rescue option when other regimens have been exhausted 4, 1, 3

Special Populations

In patients with penicillin allergy, bismuth quadruple therapy is the first choice since it contains tetracycline instead of amoxicillin 4, 1, 3. However, consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as amoxicillin resistance remains rare (<5%) 2

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 4, 1, 2, 3. Never use serology to confirm eradication—antibodies persist long after successful treatment 3

Critical Pitfalls to Avoid

• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates 2
• Avoid repeating clarithromycin if the patient has prior macrolide exposure (for any indication), as cross-resistance is universal within the macrolide family 2
• Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance 4, 1
• Never use concomitant antacids with PPIs during treatment, as this reduces efficacy 2
• Clarithromycin and levofloxacin should never be reused after treatment failure due to high resistance rates, while amoxicillin and tetracycline can be reused because resistance remains rare 3

Adjunctive Therapies

Probiotics can be used as adjunctive treatment to reduce antibiotic-associated diarrhea (which occurs in 21-41% of patients) and improve compliance, but have no proven benefit for improving eradication rates 4, 1, 2, 5