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

H. pylori Diagnosis and Treatment in Adults

First-Line Treatment Recommendation

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection in adults, consisting of a PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2

This recommendation is based on:

• Eradication rates of 80-90% even in areas with high clarithromycin and metronidazole resistance 1, 2
• No bacterial resistance to bismuth has been described, making it effective against resistant strains 1, 2
• Clarithromycin resistance now exceeds 15-20% in most of North America and Europe, rendering traditional triple therapy inadequate with only 70% eradication rates 1

Specific Dosing Regimen

• PPI (esomeprazole or rabeprazole preferred): 40 mg twice daily, taken 30 minutes before meals 1
• Bismuth subsalicylate: 262 mg (2 tablets) four times daily 1
• Metronidazole: 500 mg three to four times daily (total 1.5-2 g daily) 1
• Tetracycline: 500 mg four times daily 1
• Duration: 14 days mandatory 1, 2

Alternative First-Line Option When Bismuth Unavailable

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

• PPI twice daily
• Amoxicillin 1000 mg twice daily 3
• Clarithromycin 500 mg twice daily
• Metronidazole 500 mg twice daily

This regimen should only be used when bismuth is not available, as it includes clarithromycin which has increasing resistance rates globally. 1, 2

Critical Optimization Factors

PPI Selection and Dosing

• High-dose PPI twice daily is mandatory - standard once-daily dosing significantly reduces efficacy 1, 2
• Esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8-12% compared to other PPIs 1
• Take 30 minutes before meals on an empty stomach, without concomitant antacids 1

Treatment Duration

• 14 days is superior to shorter regimens, improving eradication by approximately 5% compared to 7-10 day courses 1, 2, 4

Antibiotic Selection Based on Resistance

• Avoid clarithromycin-based triple therapy in regions where clarithromycin resistance exceeds 15% 1, 2
• When clarithromycin-resistant strains are present, eradication rates drop from 90% to approximately 20% 1

Second-Line Treatment After First-Line Failure

After failure of clarithromycin-containing therapy: 2, 5

• Use bismuth quadruple therapy for 14 days (if not previously used) 2, 5

After failure of bismuth quadruple therapy: 2, 5

• Levofloxacin-based triple therapy for 14 days (if no prior fluoroquinolone exposure):
  • PPI twice daily
  • Amoxicillin 1000 mg twice daily 3
  • Levofloxacin 500 mg once daily or 250 mg twice daily 2

Critical caveat: Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 1, 2

Third-Line and Rescue Therapies

After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment. 1, 2, 5

When susceptibility testing is unavailable: 5

• Rifabutin-based triple therapy for 14 days: 1, 2, 5

  • Rifabutin 150 mg twice daily
  • Amoxicillin 1000 mg twice daily 3
  • PPI twice daily

• High-dose dual amoxicillin-PPI therapy for 14 days (alternative rescue option): 1

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

Verification of Eradication

Confirm eradication with urea breath test or monoclonal stool antigen test: 1, 2

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

Never use serology to confirm eradication - antibodies persist long after successful treatment. 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 enable amoxicillin use, as amoxicillin resistance remains rare (<5%) 1

Renal Impairment

• Patients with GFR <30 mL/min should NOT receive the 875 mg amoxicillin dose 3
• For GFR 10-30 mL/min: 500 mg or 250 mg every 12 hours 3
• For GFR <10 mL/min: 500 mg or 250 mg every 24 hours 3

Common Pitfalls and How to Avoid Them

Inadequate PPI Dosing

• Always use high-dose PPI twice daily - this is the single most common correctable error 1, 2
• Standard once-daily dosing reduces efficacy by 6-10% 1

Repeating Failed Antibiotics

• Never re-use clarithromycin or levofloxacin after previous exposure, even for non-H. pylori indications 1, 2
• Cross-resistance is universal within the macrolide family 1

Insufficient Treatment Duration

• Never prescribe less than 14 days for any H. pylori regimen 1, 2, 4
• 7-day regimens are obsolete and achieve unacceptably low eradication rates 1

Assuming Low Clarithromycin Resistance

• Do not use clarithromycin-based triple therapy without local surveillance data showing resistance <15% 1
• Most regions now have resistance rates exceeding 20% 1

Poor Patient Compliance

• Address compliance issues, as more than 10% of patients are poor compliers 1
• Consider adjunctive probiotics to reduce antibiotic-associated diarrhea (occurs in 21-41% of patients) and improve compliance 1

Patient Factors Affecting Success

• Smoking increases risk of eradication failure (odds ratio 1.95) 1
• High BMI/obesity leads to lower drug concentrations at the gastric mucosal level 1
• Poor compliance is a major cause of treatment failure - ensure patients understand the importance of completing the full 14-day course 6, 7