What is the recommended treatment for a patient suspected of having Helicobacter pylori (H. pylori) infection?

Treatment of Helicobacter pylori Infection

For treatment-naive patients with suspected or confirmed H. pylori infection, bismuth quadruple therapy for 14 days is the preferred first-line regimen, consisting of high-dose PPI (esomeprazole or rabeprazole 40 mg) twice daily, bismuth subsalicylate 2 tablets four times daily, tetracycline 500 mg four times daily, and metronidazole 500 mg four times daily. 1, 2, 3

Initial Diagnostic Approach

Who to test:

• Patients under 45 years with dyspeptic symptoms without alarm symptoms (anemia, weight loss, dysphagia, palpable mass) should undergo non-invasive H. pylori testing 4, 2
• Patients over 45 years with new dyspeptic symptoms or any patient with alarm symptoms require endoscopy, not empiric testing 4, 2
• All patients with active or past peptic ulcer disease, first-degree relatives of gastric cancer patients, and those with gastric MALT lymphoma require testing 1, 3

Critical testing pitfall: Never perform H. pylori testing while patients are taking PPIs (discontinue ≥2 weeks before), antibiotics, bismuth, or sucralfate (discontinue ≥4 weeks before), as these suppress but do not eradicate the bacteria, yielding false-negative results 1, 2

First-Line Treatment Regimens

Bismuth quadruple therapy (BQT) - Preferred for all patients: 1, 2, 3, 5

• Esomeprazole or rabeprazole 40 mg twice daily (30 minutes before meals)
• Bismuth subsalicylate 2 tablets (524 mg) four times daily (30 minutes before meals)
• Tetracycline 500 mg four times daily (30 minutes after meals)
• Metronidazole 500 mg four times daily (30 minutes after meals)
• Duration: 14 days (superior to 7 days with ~5% improvement in eradication rates) 4, 1

Why BQT is preferred: This regimen avoids clarithromycin entirely, which has resistance rates exceeding 15-20% in most North American regions, making empiric clarithromycin-based triple therapy obsolete 4, 1, 5

Alternative first-line option (rifabutin triple therapy): 1, 3

• Rifabutin 150 mg twice daily
• Amoxicillin 1 gram three times daily
• Esomeprazole or rabeprazole 40 mg twice daily
• Duration: 14 days

Critical PPI selection: Use esomeprazole 40 mg or rabeprazole 40 mg twice daily—avoid pantoprazole due to inferior potency (40 mg pantoprazole equals only 9 mg omeprazole equivalent, which is inadequate) 1

Regimens to Avoid

Never use these empirically without confirmed susceptibility: 1

• Clarithromycin triple therapy (only with confirmed susceptibility)
• Levofloxacin triple therapy (only with confirmed susceptibility)
• Metronidazole triple therapy (only with confirmed susceptibility)
• Concomitant, hybrid, reverse hybrid, or sequential therapies (expose patients to antibiotics providing no benefit while increasing global antimicrobial resistance) 1

Second-Line Treatment After First-Line Failure

If BQT was not used previously: 1, 2, 3

• Optimized bismuth quadruple therapy for 14 days (same regimen as above, ensuring high-dose PPI and full 14-day duration)

If BQT was used previously: 1, 3

• Levofloxacin 500 mg once daily + amoxicillin 1 gram twice daily + PPI twice daily for 14 days
• Caution: Rising levofloxacin resistance rates must be considered; local surveillance data should guide this choice 4, 1

After multiple treatment failures: 4, 1

• Antimicrobial susceptibility testing should be performed whenever possible
• Culture-based testing available through Mayo Clinic, ARUP, Labcorp, Quest Diagnostics 4
• Molecular testing (next-generation sequencing) available through American Molecular Laboratories for susceptibility to amoxicillin, clarithromycin, levofloxacin, tetracycline, metronidazole, and rifabutin 4

Special Populations

Patients with penicillin allergy: 1, 2

• In areas with low clarithromycin resistance (<15%): PPI-clarithromycin-metronidazole for 14 days
• In areas with high clarithromycin resistance (≥15%): Bismuth quadruple therapy (does not contain penicillin)

Pediatric patients: 2

• Treatment must be conducted by pediatric specialists in specialized centers, not primary care
• Weight-based dosing is mandatory
• Tetracycline contraindicated in children under 8 years (permanent tooth discoloration, impaired bone growth)
• Fluoroquinolones should be avoided (cartilage damage, tendon rupture risk)

Confirmation of Eradication (Test-of-Cure)

All patients require test-of-cure at least 4 weeks after completing treatment: 4, 1, 2, 3

• Preferred methods: Urea breath test (88-95% sensitivity, 95-100% specificity) or laboratory-based validated monoclonal stool antigen test (>90% sensitivity and specificity) 4, 1, 3
• PPIs must be discontinued ≥2 weeks before testing to avoid false-negative results 1, 2
• Antibiotics and bismuth must be discontinued ≥4 weeks before testing 1

Why test-of-cure is mandatory: Provides indirect measure of resistance/susceptibility in the population, distinguishes locally successful regimens from those that should be avoided, and ensures eradication in high-risk patients 4, 3

Endoscopy-based testing required for: 1

• Complicated peptic ulcer disease
• Gastric ulcer (repeat endoscopy with biopsy until healed to exclude malignancy)
• Gastric MALT lymphoma

Key Clinical Principles

Treatment duration: 14 days is optimal and superior to 7 days for all regimens 4, 1, 3

Antibiotic resistance is the most important factor causing treatment failure: 4, 1, 2, 3

• Local surveillance of resistance patterns is mandatory for optimal treatment selection
• Exclude antibiotics where preexisting resistance is likely by thorough history of prior antibiotic use 4
• Review medical and pharmacy records for prior antibiotic exposures 4

Patient adherence is crucial: 1, 3

• Incomplete treatment leads to antibiotic resistance and treatment failure
• Ensure patients understand the importance of completing the full 14-day course
• Take medications at the start of meals to minimize gastrointestinal intolerance 6

Surveillance After Eradication

For patients with gastric atrophy or intestinal metaplasia: 4

• Moderate to severe or multifocal gastric atrophy/intestinal metaplasia requires endoscopic surveillance every 3 years
• Shorter intervals may be advisable in those with multiple risk factors (family history of gastric cancer, extensive anatomic involvement)

For patients with normal mucosa after eradication: 4

• If first-degree family history of gastric cancer or persistent H. pylori infection despite eradication attempts: screening endoscopy every 3-5 years
• Without additional risk factors: further endoscopies for gastric cancer screening are not advised