What is the recommended testing and treatment approach for a patient with a suspected Helicobacter pylori (H. pylori) infection?

H. pylori Testing and Treatment Approach

For patients with suspected H. pylori infection, perform non-invasive testing with urea breath test (UBT) or laboratory-based monoclonal stool antigen test, and if positive, treat with bismuth quadruple therapy for 14 days, followed by mandatory test-of-cure at least 4 weeks after completing treatment. 1, 2, 3

Diagnostic Testing Strategy

Non-Invasive Testing (Preferred for Most Patients)

• Urea breath test (UBT) is the gold standard non-invasive test with sensitivity of 88-95% (up to 94.7-97% for test-of-cure) and specificity of 95-100% 4, 5
• Laboratory-based monoclonal stool antigen test has sensitivity of 94% and specificity of 92%, and is an acceptable alternative to UBT 4, 1
• These tests are appropriate for patients under 45-55 years without alarm symptoms (weight loss, dysphagia, bleeding, anemia, persistent vomiting) 2

Endoscopy-Based Testing (For Specific Situations)

• Patients over 45 years with new dyspeptic symptoms or any patient with alarm symptoms require endoscopy with biopsy for H. pylori testing 2
• Endoscopic testing is also indicated for patients with suspected peptic ulcer disease or gastric cancer 4
• Histologic examination with immunohistochemical staining provides definitive diagnosis when organisms are difficult to visualize 4

Critical Testing Requirements to Avoid False Results

• Discontinue PPIs for at least 2 weeks (preferably) before testing - PPIs cause false-negative results by suppressing bacterial load 4, 1, 2
• Withhold antibiotics and bismuth for at least 4 weeks before testing - these medications can eradicate or suppress H. pylori, causing false-negative results 1, 2
• Never use serology for diagnosis or test-of-cure - antibody levels remain elevated long after successful eradication and cannot distinguish active from past infection 4, 1
• Avoid rapid in-office stool tests - they have significantly lower accuracy than laboratory-based monoclonal antibody tests 1

First-Line Treatment Regimens

Bismuth Quadruple Therapy (Preferred)

Bismuth quadruple therapy for 14 days is the preferred first-line treatment in North America due to high clarithromycin resistance rates (>15%). 1, 2, 3

• Regimen components: PPI twice daily + bismuth subsalicylate + tetracycline 500 mg four times daily + metronidazole 500 mg four times daily 5, 2
• This regimen achieves superior eradication rates without requiring susceptibility testing 5, 2
• High-dose PPI (twice daily) increases eradication success by approximately 5% 2
• 14-day duration is mandatory - significantly superior to 7-day courses 1, 2

Alternative First-Line Options

• Standard triple therapy (PPI + clarithromycin + amoxicillin for 14 days) achieves eradication rates near 90% only in areas with low clarithromycin resistance (<15%) 1, 6
• For penicillin allergy: Use bismuth quadruple therapy (tetracycline is acceptable) or PPI-clarithromycin-metronidazole in low resistance areas 1, 2
• Rifabutin triple therapy for 14 days is a suitable empiric alternative in penicillin-allergic patients 3

Mandatory Test-of-Cure

All patients must undergo confirmation testing at least 4 weeks after completing eradication therapy - this is non-negotiable. 1, 2, 3

• Use UBT or laboratory-based stool antigen test - never serology 5, 1
• Timing is critical: Minimum 4 weeks post-treatment to allow bacterial regrowth if eradication failed 5, 2
• Discontinue PPIs for at least 2 weeks before test-of-cure to avoid false-negative results 5, 2
• Test-of-cure is essential for monitoring treatment success and tracking resistance patterns 1

Management of Treatment Failure

Second-Line Therapy

• After first-line failure: Use optimized bismuth quadruple therapy for 14 days if not previously used 2, 3
• Levofloxacin-containing triple therapy for 14 days is an alternative, but rising levofloxacin resistance limits its utility 2, 3
• Never re-use clarithromycin without confirmed susceptibility - clarithromycin resistance is the primary cause of triple therapy failure 1, 3

Antibiotic Susceptibility Testing

• Perform antimicrobial susceptibility testing after multiple treatment failures 1, 3
• Molecular resistance testing is now available from stool samples for clarithromycin, levofloxacin, and metronidazole 1
• Salvage regimens containing clarithromycin or levofloxacin should only be used if antibiotic susceptibility is confirmed 3

Special Clinical Contexts

Bleeding Peptic Ulcer

• All patients with bleeding peptic ulcer must undergo H. pylori testing 4
• H. pylori eradication significantly reduces rebleeding risk from 26% to much lower rates 4, 1
• Start eradication therapy after 72-96 hours of intravenous PPI administration 4
• In H. pylori-positive patients with prior ulcer bleeding on aspirin, confirmed eradication reduces annualized rebleeding rates from 4.6% to 1.1% 1

Gastric Cancer Prevention

• H. pylori is a Class I carcinogen causing gastric cancer through progression from chronic gastritis to atrophic gastritis to metaplasia to dysplasia to carcinoma 4
• Eradication halts the increase in gastric cancer risk and reduces overall risk, though it does not eliminate risk entirely 4
• High-risk populations (Asian descent, family history of gastric cancer, immigrants from high-prevalence areas) warrant increased screening efforts 4

Common Pitfalls to Avoid

• Do not test patients currently taking PPIs, antibiotics, or bismuth - wait for appropriate washout periods 1, 2
• Do not use 7-day treatment regimens - 14 days is superior and mandatory 1, 2
• Do not skip test-of-cure - this is essential for confirming eradication and monitoring resistance 1, 2
• Do not empirically use clarithromycin triple therapy in North America - high resistance rates (>15%) make bismuth quadruple therapy preferred 1, 2, 3
• Do not use serology to confirm eradication - antibodies persist long after successful treatment 4, 1
• Do not prescribe monotherapy or inappropriate regimens - this promotes antibiotic resistance 2

Pediatric Considerations

• H. pylori treatment in children should be conducted by pediatric specialists in specialized centers, not primary care 2
• Weight-based dosing is mandatory and differs substantially from adult regimens 2
• Tetracycline is contraindicated in children under 8 years due to permanent tooth discoloration and impaired bone growth 2
• Fluoroquinolones should be avoided in children due to cartilage damage and tendon rupture risk 2