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

Treatment of Helicobacter pylori Infection

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection, consisting of a proton pump inhibitor (PPI) twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1

First-Line Treatment Selection

Bismuth quadruple therapy should be used as the preferred first-line regimen because clarithromycin resistance now exceeds 15% in most regions of North America and Europe, making traditional triple therapy unacceptably ineffective with eradication rates dropping to approximately 70%—well below the 80% minimum target. 1

Bismuth Quadruple Therapy Regimen:

• PPI (esomeprazole or rabeprazole 40 mg) twice daily 1
• Bismuth subsalicylate 1
• Metronidazole 1
• Tetracycline HCl 1
• Duration: 14 days (preferred over 10 days to maximize eradication rates) 1

This regimen achieves 80-90% eradication rates even against metronidazole-resistant strains due to the synergistic effect of bismuth, and bacterial resistance to bismuth is extremely rare. 1

Alternative First-Line Option (When Bismuth is Unavailable):

Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth cannot be used: 1

• PPI twice daily 1
• Amoxicillin 1000 mg twice daily 1
• Clarithromycin 500 mg twice daily 1
• Metronidazole 500 mg twice daily 1

This regimen administers all antibiotics simultaneously, preventing the development of resistance during treatment. 1

Triple Therapy (Only in Low Clarithromycin Resistance Areas):

Triple therapy may only be considered in regions with documented clarithromycin resistance <15%: 1

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

Critical caveat: Standard triple therapy should be abandoned when regional clarithromycin resistance exceeds 15-20%, as eradication rates drop to approximately 20% with resistant strains compared to 90% with susceptible strains. 1

Optimizing Treatment Success

PPI Dosing:

• Always use high-dose PPI twice daily (not once daily), as this increases eradication efficacy by 6-10% by reducing gastric acidity and enhancing antibiotic activity. 1, 2
• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by 8-12% compared to other PPIs. 1

Treatment Duration:

• 14-day duration is strongly preferred over 7-day regimens, as extending treatment improves eradication success by approximately 5%. 1

Administration:

• Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance. 3

Adjunctive Therapy:

• Consider probiotics to reduce diarrhea (which occurs in 21-41% of patients during the first week) and improve patient compliance. 1

Second-Line Treatment (After First-Line Failure)

If Bismuth Quadruple Therapy Was Not Used First-Line:

• Bismuth quadruple therapy for 14 days 1, 2

If Bismuth Quadruple Therapy Has Already Been Used:

• Levofloxacin-based triple therapy for 14 days: 1, 2
  • PPI twice daily
  • Amoxicillin 1000 mg twice daily
  • Levofloxacin 500 mg once daily (or 250 mg twice daily)

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

Alternative Second-Line Option:

• Rifabutin-based triple therapy for 14 days is highly effective as rescue therapy after previous treatment failures: 1, 2
  • PPI twice daily
  • Amoxicillin 1000 mg twice daily
  • Rifabutin 150 mg twice daily

Rifabutin has the advantage of rare bacterial resistance, making it particularly valuable for persistent infections. 1, 2

Third-Line and Rescue Therapy

After two failed eradication attempts, antimicrobial susceptibility testing should guide further treatment whenever possible. 1, 2

When susceptibility testing is unavailable:

• Avoid repeating antibiotics previously used, especially clarithromycin and levofloxacin, due to cross-resistance. 1, 2
• High-dose dual therapy (PPI twice daily + amoxicillin 1000 mg twice daily) for 14 days is an alternative rescue option. 1
• Consider rifabutin-based therapy if not previously used. 1

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test:

• At least 4 weeks after completion of therapy 1, 2, 4
• At least 2 weeks after PPI discontinuation 1, 2, 4

Do not use serology to confirm eradication, as antibodies may persist long after successful treatment. 2, 4

Critical Pitfalls to Avoid

• Never use standard-dose PPI once daily—always use twice-daily dosing to maximize gastric pH elevation. 1
• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates. 1
• Never repeat clarithromycin if the patient has prior macrolide exposure (for any indication), as cross-resistance is universal within the macrolide family. 1
• Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates and FDA warnings about serious side effects. 1
• Verify penicillin allergy before avoiding amoxicillin—consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare. 1

Patient Factors Affecting Success

• Smoking increases risk of eradication failure (odds ratio 1.95 for smokers versus non-smokers). 1
• High BMI, especially in obese patients, increases risk of failure due to lower drug concentrations at the gastric mucosal level. 1
• Ensure patient adherence by counseling about the importance of completing the full 14-day course. 1