What is the recommended treatment regimen for H pylori (Helicobacter pylori) infection?

H. pylori Treatment Regimens

For first-line H. pylori eradication, use 14-day bismuth quadruple therapy (bismuth ~300mg four times daily, metronidazole 500mg three times daily, tetracycline 500mg four times daily, and PPI twice daily) as the preferred regimen, particularly in areas with clarithromycin resistance >15%. 1, 2

First-Line Treatment Selection Based on Local Resistance Patterns

In areas with high clarithromycin resistance (>15-20%):

• Bismuth quadruple therapy for 14 days is the strongly recommended first-line option 1, 2
• If bismuth is unavailable, use concomitant non-bismuth quadruple therapy (PPI twice daily, amoxicillin 1000mg twice daily, metronidazole 500mg twice daily, clarithromycin 500mg twice daily) for 14 days 1, 3
• Standard clarithromycin-containing triple therapy should be abandoned when clarithromycin resistance exceeds 15-20% 1, 2

In areas with low clarithromycin resistance (<15%):

• Clarithromycin-containing triple therapy (PPI twice daily, clarithromycin 500mg twice daily, amoxicillin 1000mg twice daily) for 14 days is acceptable 1, 2
• Bismuth quadruple therapy remains an alternative first-line option 1

Critical Treatment Optimization Factors

PPI dosing is crucial for success:

• Use high-dose PPI (twice daily) rather than standard dosing, which increases eradication efficacy by 6-10% 1, 2, 4
• Standard PPI doses: pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, dexlansoprazole 30mg, rabeprazole 20mg 1
• Administer PPI 30 minutes before eating on an empty stomach 1

Treatment duration matters:

• All first-line regimens should be 14 days in duration 1, 2
• Extending from 7 to 14 days improves eradication success by approximately 5% 1, 2, 4

Second-Line Treatment After First-Line Failure

After clarithromycin-containing triple therapy fails:

• Use bismuth quadruple therapy for 14 days (if not previously used) 1
• Alternative: levofloxacin triple therapy (PPI twice daily, levofloxacin 500mg once daily, amoxicillin 1000mg twice daily) for 14 days 1

After bismuth quadruple therapy fails:

• Use levofloxacin triple therapy for 14 days 1
• Consider high-dose dual therapy (amoxicillin 2-3g daily in 3-4 split doses, high-dose PPI twice daily) for 14 days 1

Third-Line and Rescue Therapy

After two failed eradication attempts:

• Antimicrobial susceptibility testing should guide further treatment selection 1, 2
• If susceptibility testing is unavailable, use rifabutin triple therapy (rifabutin 150-300mg daily, amoxicillin 1000mg twice daily, PPI twice daily) for 10 days 1
• Rifabutin can be prescribed without prior susceptibility testing since rifabutin and amoxicillin resistance are rare 1

Specific Regimen Details

Bismuth quadruple therapy:

• Bismuth subsalicylate ~300mg four times daily
• Metronidazole 500mg three times daily
• Tetracycline 500mg four times daily
• PPI standard dose twice daily
• Duration: 14 days (10-14 days acceptable if 10 days proven locally effective) 1

Concomitant non-bismuth quadruple therapy:

• PPI standard dose twice daily
• Amoxicillin 1000mg twice daily
• Metronidazole 500mg twice daily
• Clarithromycin 500mg twice daily
• Duration: 14 days 1

Levofloxacin triple therapy:

• PPI standard dose twice daily
• Levofloxacin 500mg once daily (or 250mg twice daily)
• Amoxicillin 1000mg twice daily
• Duration: 14 days 1

Testing for H. pylori Infection

Non-invasive testing options:

• Urea breath test: sensitivity 88-95%, specificity 95-100% 1
• Stool antigen testing: sensitivity 94%, specificity 92% 1
• Both are acceptable for initial diagnosis and confirmation of eradication 1, 2

Confirmation of eradication:

• Test at least 4 weeks after completing therapy 2, 4
• Test at least 2 weeks after discontinuing PPI 2, 4
• Do not use serology to confirm eradication, as antibodies persist after successful treatment 2, 4

Common Pitfalls and How to Avoid Them

Inadequate acid suppression:

• Always use high-dose (twice daily) PPI, not standard once-daily dosing 1, 2, 4
• Avoid concomitant use of H2-receptor antagonists with PPIs 1

Insufficient treatment duration:

• Do not use 7-day regimens; 14 days is the recommended standard 1, 2
• The Toronto Consensus specifically recommends 14 days for all first-line treatments to maximize first-attempt success 1

Ignoring local resistance patterns:

• Clarithromycin resistance is the primary reason for triple therapy failure, with global resistance rates reaching 17.6% 1
• In regions where clarithromycin resistance exceeds 15-20%, standard triple therapy achieves only 70% eradication rates, well below the 80% minimum target 1

Sequential therapy limitations:

• Sequential therapy (5 days PPI + amoxicillin, followed by 5 days PPI + clarithromycin + metronidazole) is not recommended as a first-line option by recent consensus guidelines 1
• This regimen is considered a non-ideal option compared to bismuth quadruple or concomitant therapy 1

Adjunctive Therapies

Probiotics:

• May reduce antibiotic-associated side effects 1, 2, 4
• Evidence for improving eradication rates is limited and considered experimental for refractory infection 1
• Can improve compliance by reducing diarrhea 4

Special Populations

Bleeding peptic ulcer patients:

• Start standard triple therapy after 72-96 hours of intravenous PPI administration 1
• Administer for 14 days 1
• All patients with bleeding peptic ulcer should undergo H. pylori testing 1

Renal impairment:

• For GFR 10-30 mL/min: 500mg or 250mg amoxicillin every 12 hours 5
• For GFR <10 mL/min: 500mg or 250mg amoxicillin every 24 hours 5
• Hemodialysis patients: administer additional dose during and at end of dialysis 5