What is the recommended treatment for a patient with a suspected 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 a PPI twice daily, bismuth subsalicylate, tetracycline 500 mg four times daily, and metronidazole 500 mg four times daily, taken at the start of meals. 1, 2, 3, 4

Initial Patient Assessment and Testing Strategy

Age-Based Triage

• Patients under 45 years without alarm symptoms (anemia, weight loss, dysphagia, palpable mass, malabsorption) can be tested non-invasively for H. pylori and treated empirically without endoscopy 1, 3
• Patients over 45 years with new dyspeptic symptoms or any patient with alarm symptoms must be referred for endoscopy before treatment to exclude gastric malignancy 1, 3
• Rule out family history of gastric cancer before proceeding with empiric treatment in younger patients 1

Diagnostic Testing Options

• Urea breath test (UBT) is the most accurate non-invasive method with sensitivity 94.7-97% and specificity 95-100% 2, 5
• Laboratory-based validated monoclonal stool antigen test is an acceptable alternative when UBT is unavailable 1
• Serology alone is unreliable for treatment decisions and should not be used for post-treatment confirmation 1
• Discontinue PPIs at least 2 weeks before testing to avoid false-negative results 3

First-Line Treatment Regimens

Bismuth Quadruple Therapy (Preferred)

This is the preferred regimen in areas of high clarithromycin resistance (>15%), which now includes most of North America and Europe. 1, 3, 4

Components for 14 days:

• PPI (high-dose, twice daily) 1
• Bismuth subsalicylate 1, 2
• Tetracycline 500 mg four times daily 1, 2, 6
• Metronidazole 500 mg four times daily 1, 2

Critical optimization factors:

• Duration must be 14 days (superior to 7 days) 1, 3
• High-dose PPI twice daily increases eradication success by approximately 5% 3
• All medications should be taken at the start of meals to minimize gastrointestinal intolerance 6

Alternative First-Line Regimens (When BQT Unavailable)

• Concomitant non-bismuth quadruple therapy for 14 days: PPI, amoxicillin, clarithromycin, and metronidazole (only in areas with clarithromycin resistance <15%) 1, 7, 8
• Rifabutin triple therapy for 14 days is suitable for patients without penicillin allergy 4

Penicillin Allergy Considerations

• In low clarithromycin resistance areas: PPI-clarithromycin-metronidazole for 14 days 1, 3
• In high clarithromycin resistance areas: bismuth quadruple therapy remains preferred (tetracycline is not a penicillin) 1, 3

Second-Line Treatment After First Failure

After failure of initial therapy, optimized bismuth quadruple therapy for 14 days is preferred if BQT was not used previously. 3, 4

Alternative Second-Line Options

• Levofloxacin triple therapy for 14 days (PPI, levofloxacin, amoxicillin) in areas of low fluoroquinolone resistance 1, 3
• Critical caveat: Never use levofloxacin in patients with chronic bronchopneumopathy who may have received fluoroquinolones previously 1
• Rising levofloxacin resistance rates limit this option's effectiveness 1, 3

Third-Line and Salvage Therapy

After failure of second-line therapy, treatment should be guided by antimicrobial susceptibility testing whenever possible. 1

Susceptibility Testing Options

• Culture of gastric biopsies is available from major reference laboratories (Mayo Clinic, ARUP, Labcorp, Quest Diagnostics) 1
• Molecular antimicrobial resistance testing using next-generation sequencing is available for clarithromycin, levofloxacin, metronidazole, amoxicillin, tetracycline, and rifabutin 1
• Reflex stool testing automatically performs susceptibility testing if H. pylori stool antigen is positive 1

Empiric Third-Line Options (When Testing Unavailable)

• Use antibiotics not previously prescribed 1, 8
• Rifabutin-containing regimens 1
• High-dose PPI/amoxicillin therapy 9
• Furazolidone-containing regimens (where available) 9, 8

Confirmation of Eradication (Test of Cure)

All patients must undergo test-of-cure at least 4 weeks after completing treatment. 1, 3

Testing Method and Timing

• UBT or laboratory-based validated monoclonal stool antigen test are the only acceptable methods 1, 2
• Serology has no role in confirming eradication 1
• Minimum 4 weeks after treatment completion 1, 2
• PPIs must be discontinued at least 2 weeks before testing 3
• Antibiotics must be discontinued at least 4 weeks before testing 5

Critical Pitfalls to Avoid

Antibiotic Resistance

• Clarithromycin, metronidazole, and fluoroquinolone triple therapies can no longer be used empirically due to widespread resistance 1
• Antibiotic resistance is the most important factor responsible for eradication failure 3
• Local surveillance of resistance patterns is mandatory for optimal treatment selection 3

Patient Compliance

• Poor compliance is a major cause of treatment failure 7
• Counsel patients on the importance of completing the full 14-day course 7, 3
• Smoking and high BMI increase risk of eradication failure (OR 1.95 for smoking) 7

Testing Errors

• Never perform H. pylori testing while patient is taking PPIs, antibiotics, or sucralfate within specified washout periods 3, 5
• False-negative results occur with active bleeding ulcers 5

Inappropriate Regimens

• Avoid monotherapy or suboptimal regimens to minimize development of antibiotic resistance 3, 9
• Never use 7-day regimens when 14-day therapy is indicated 1, 3

Special Populations

Pediatric Patients

• H. pylori treatment in children must be conducted by pediatric specialists in specialized centers, not in primary care 3
• Weight-based dosing is mandatory and differs substantially from adult regimens 3
• Tetracycline is contraindicated in children under 8 years due to risk of permanent tooth discoloration and impaired bone growth 3
• Fluoroquinolones should be avoided in children due to risk of cartilage damage and tendon rupture 3

H. pylori with Duodenal Ulcer Disease (Adults Only)

• Triple therapy: Amoxicillin 1 gram, clarithromycin 500 mg, and lansoprazole 30 mg, all twice daily for 14 days 6
• Dual therapy (for clarithromycin allergy/resistance): Amoxicillin 1 gram and lansoprazole 30 mg, both three times daily for 14 days 6

Renal Impairment

• Patients with GFR <30 mL/min should NOT receive the 875 mg amoxicillin dose 6
• GFR 10-30 mL/min: 500 mg or 250 mg every 12 hours 6
• GFR <10 mL/min: 500 mg or 250 mg every 24 hours 6
• Hemodialysis: Administer additional dose during and at end of dialysis 6