What are the recommended treatment regimens and dosages for H. pylori infection?

H. pylori Treatment Regimens and Dosages

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a PPI twice daily, bismuth subsalicylate 524 mg (or 262 mg as 2 tablets) four times daily, metronidazole 500 mg three to four times daily (total 1.5-2 g daily), and tetracycline 500 mg four times daily. 1, 2, 3

First-Line Treatment Options

Bismuth Quadruple Therapy (Preferred)

• PPI (high-dose): Esomeprazole or rabeprazole 40 mg twice daily, taken 30 minutes before meals on an empty stomach 1, 2
• Bismuth subsalicylate: 524 mg four times daily (or 262 mg as 2 tablets four times daily) 1, 3
• Metronidazole: 500 mg three to four times daily (total daily dose 1.5-2 g) 1, 2, 3
• Tetracycline: 500 mg four times daily 1, 2
• Duration: 14 days (mandatory to maximize eradication rates of 80-90%) 1, 2, 4

This regimen is preferred because bacterial resistance to bismuth is extremely rare, and it achieves high eradication rates even against strains resistant to clarithromycin and metronidazole. 1, 2, 3

Alternative First-Line: Concomitant Non-Bismuth Quadruple Therapy

• PPI (high-dose): Twice daily 1, 2
• Amoxicillin: 1000 mg twice daily 1, 2, 5
• Clarithromycin: 500 mg twice daily 1, 2
• Metronidazole: 500 mg twice daily 1, 2
• Duration: 14 days 1, 2

This regimen should only be used when bismuth is unavailable, as it includes clarithromycin which has increasing resistance rates globally (>15-20% in most regions). 1, 2

Triple Therapy (Only in Low Clarithromycin Resistance Areas <15%)

• PPI (high-dose): Twice daily 1, 2
• Amoxicillin: 1000 mg twice daily 1, 2, 5
• Clarithromycin: 500 mg twice daily 1, 2
• Duration: 14 days 1, 2

Critical caveat: This regimen should be abandoned in most North American and European regions where clarithromycin resistance now exceeds 15%, as eradication rates drop to only 20% with resistant strains compared to 90% with susceptible strains. 1, 2

Second-Line Treatment After First-Line Failure

If Bismuth Quadruple Therapy Not Previously Used

• Use the bismuth quadruple therapy regimen detailed above for 14 days 1, 2, 4

Levofloxacin Triple Therapy (If No Prior Fluoroquinolone Exposure)

• PPI (high-dose): Twice daily 1, 2
• Amoxicillin: 1000 mg twice daily 1, 2, 5
• Levofloxacin: 500 mg once daily OR 250 mg twice daily 1, 2
• Duration: 14 days 1, 2

Important warning: Levofloxacin resistance rates are rising (11-30% primary, 19-30% secondary), and the FDA recommends fluoroquinolones be used as a last choice due to serious side effects. 1, 2

Third-Line and Rescue Therapies

Rifabutin Triple Therapy

• PPI (high-dose): Twice daily 1, 2
• Amoxicillin: 1000 mg twice daily 1, 2, 5
• Rifabutin: 150 mg twice daily 1, 2
• Duration: 14 days 1, 2

Rifabutin resistance is extremely rare, making this an effective rescue option after multiple treatment failures. 1, 2

High-Dose Dual Amoxicillin-PPI Therapy

• Amoxicillin: 2-3 grams daily in 3-4 divided doses 1, 2
• PPI (high-dose): Double standard dose, twice daily 1, 2
• Duration: 14 days 1, 2

This is reserved for patients who have exhausted other options. 1, 2

After Two Failed Attempts

• Antibiotic susceptibility testing should guide further treatment whenever possible 1, 2, 4
• Molecular testing for clarithromycin and levofloxacin resistance can guide therapy selection earlier 1

FDA-Approved Regimens for H. pylori (Adults)

Triple Therapy with Lansoprazole

• Amoxicillin: 1 gram twice daily (every 12 hours) 5
• Clarithromycin: 500 mg twice daily 5
• Lansoprazole: 30 mg twice daily 5
• Duration: 14 days 5

Dual Therapy with Lansoprazole

• Amoxicillin: 1 gram three times daily (every 8 hours) 5
• Lansoprazole: 30 mg three times daily 5
• Duration: 14 days 5

Critical Optimization Factors

PPI Dosing

• Always use high-dose PPI twice daily (not standard once-daily dosing), as this increases cure rates by 6-12% 1, 2
• Esomeprazole or rabeprazole 40 mg twice daily are preferred over other PPIs, increasing cure rates by an additional 8-12% 1, 2
• Take 30 minutes before meals on an empty stomach, without concomitant antacids 1, 2

Treatment Duration

• 14 days is mandatory for all regimens, as it improves eradication success by approximately 5% compared to 7-10 day regimens 1, 2, 4

Antibiotic Selection

• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 1, 2
• Amoxicillin and tetracycline can be re-used because resistance remains rare (<5%) 1, 2
• Metronidazole can be re-used with bismuth because bismuth's synergistic effect 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
• Consider penicillin allergy testing to delist the allergy and enable amoxicillin use 1, 2

Renal Impairment (Amoxicillin Dosing)

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

Pediatric Patients (>3 months, <40 kg)

• Amoxicillin: 45 mg/kg/day in divided doses every 12 hours (or 40 mg/kg/day every 8 hours) for severe infections 5
• Avoid fluoroquinolones and tetracyclines in children 2
• Treatment should only be conducted by pediatricians in specialist centers 1

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 1, 2, 4
• Never use serology to confirm eradication, as antibodies persist long after successful treatment 1, 2

Common Pitfalls to Avoid

• Inadequate PPI dosing: Standard once-daily PPI is inadequate; always use twice-daily high-dose PPI 1, 2
• Assuming low clarithromycin resistance: Most regions now have resistance >15-20%; do not use triple therapy empirically without local surveillance data 1, 2
• Repeating failed antibiotics: Avoid re-using clarithromycin or levofloxacin after exposure, as cross-resistance is universal 1, 2
• Short treatment duration: 7-10 day regimens are inferior; always use 14 days 1, 2, 4

Adjunctive Measures

• Probiotics can reduce antibiotic-associated diarrhea (occurs in 21-41% of patients) and improve compliance, though evidence for increasing eradication rates is limited 1, 2, 6
• Smoking cessation should be encouraged, as smoking increases eradication failure risk (OR 1.95) 1
• Address compliance issues, as >10% of patients are poor compliers, leading to much lower eradication rates 1