What is the recommended first-line treatment regimen, including specific doses, for managing H pylori (Helicobacter pylori) infection?

H. pylori Infection Management with Specific Doses

For treatment-naive patients, bismuth quadruple therapy for 14 days is the first-line treatment: PPI twice daily + bismuth ~300mg four times daily + metronidazole 500mg three times daily + tetracycline 500mg four times daily. 1, 2

First-Line Treatment Regimens

Bismuth Quadruple Therapy (Preferred)

• PPI standard dose twice daily (pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, dexlansoprazole 30mg, or rabeprazole 20mg) 1
• Bismuth subsalicylate 262mg, 2 tablets four times daily OR bismuth subcitrate 120mg, 1 tablet four times daily 1
• Metronidazole 500mg three to four times daily (total 1.5-2g daily) 1, 2
• Tetracycline 500mg four times daily 1, 2
• Duration: 14 days 1, 2, 3

This regimen achieves 80-90% eradication rates even against metronidazole-resistant strains due to bismuth's synergistic effect, and bacterial resistance to bismuth is extremely rare. 2, 4

Concomitant Non-Bismuth Quadruple Therapy (Alternative First-Line)

• PPI standard dose twice daily 1, 2
• Amoxicillin 1000mg twice daily 1
• Clarithromycin 500mg twice daily 1
• Metronidazole 500mg twice daily 1
• Duration: 14 days 1, 2

Use this regimen only when bismuth is unavailable or in areas with documented low clarithromycin resistance (<15%). 1, 2, 4

PPI Triple Therapy (Restricted Use)

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

Critical restriction: Only use in areas with documented clarithromycin resistance <15%, as eradication rates drop from 90% to 20% with resistant strains. 1, 2, 4 Most regions in North America and Europe now exceed 20% resistance. 2

Second-Line Treatment After First Failure

If Clarithromycin-Based Therapy Failed

Bismuth quadruple therapy (as detailed above) if not previously used. 1, 2

If Bismuth Quadruple Therapy Failed

Levofloxacin triple therapy:

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

Never reuse clarithromycin or levofloxacin after prior exposure—resistance develops rapidly and is essentially universal within the macrolide family. 1, 2

Third-Line and Rescue Therapies

Rifabutin Triple Therapy

• PPI standard dose twice daily 1
• Amoxicillin 1000mg twice daily 1
• Rifabutin 150mg twice daily OR 300mg once daily 1
• Duration: 10-14 days 1

Reserve for patients who have failed at least 2-3 prior regimens, as rifabutin and amoxicillin resistance remain rare. 1, 2

High-Dose Dual Therapy

• Amoxicillin 2-3 grams daily in 3-4 split doses (e.g., 750mg four times daily) 1
• PPI high-dose twice daily (double the standard dose: pantoprazole 80mg, omeprazole 40mg, etc.) 1
• Duration: 14 days 1

Consider as a rescue option when other regimens have been exhausted. 1

Critical Optimization Factors

PPI Dosing

Always use twice-daily dosing taken 30 minutes before meals on an empty stomach—standard once-daily dosing is inadequate and reduces eradication by 6-10%. 1, 2, 5, 4 Do not use concomitant H2-receptor antagonists. 1

Treatment Duration

14 days is superior to 7-10 day regimens, improving eradication by approximately 5%. 1, 2, 5, 4, 3 All three major consensus guidelines (Toronto, Maastricht V/Florence, ACG) recommend 14 days. 1, 3

Antibiotic Reuse Rules

• Never reuse: Clarithromycin, levofloxacin (resistance develops after single exposure) 1, 2
• Can reuse: Amoxicillin, tetracycline (resistance remains rare <5%) 1, 2
• Can reuse with bismuth: Metronidazole (bismuth overcomes in vitro resistance) 1, 2

Special Populations

Penicillin Allergy

Bismuth quadruple therapy is the first choice as it contains tetracycline, not amoxicillin. 1, 2 Alternatively, use clarithromycin + metronidazole triple therapy only in areas with documented low clarithromycin resistance. 1

H. pylori with Dual Therapy (FDA-Approved)

For specific FDA-approved dual therapy regimens:

• Amoxicillin 1 gram + clarithromycin 500mg + lansoprazole 30mg, all twice daily for 14 days 6
• Amoxicillin 1 gram + lansoprazole 30mg, both three times daily for 14 days 6

These regimens are less effective than quadruple therapies and should only be used in areas with very low clarithromycin resistance. 1, 2

After Two Failed Attempts

Obtain antibiotic susceptibility testing before attempting further treatment. 1, 5, 4 Molecular testing for clarithromycin and levofloxacin resistance can guide therapy selection earlier in the algorithm. 1

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy and at least 2 weeks after stopping PPIs. 2, 5, 4 Never use serology for confirmation as antibodies persist long after successful treatment. 5, 4

Common Pitfalls to Avoid

• Do not use standard once-daily PPI dosing—this significantly reduces efficacy 1, 2, 5, 4
• Do not assume low clarithromycin resistance without local surveillance data—most regions now have >15% resistance 2
• Do not use levofloxacin empirically as first-line therapy—resistance rates are 11-30% primary and 19-30% secondary 2
• Do not use sequential or hybrid therapies—concomitant therapy is superior as it prevents resistance development during treatment 2
• Confirm patient adherence before declaring treatment failure—over 10% of patients are poor compliers 2
• Consider smoking cessation counseling—smoking increases eradication failure risk (OR 1.95) 2