Treatment of H. pylori Infection
First-Line Treatment Recommendation
Bismuth quadruple therapy (BQT) for 14 days is the preferred first-line treatment for confirmed H. pylori infection, consisting of a proton pump inhibitor (PPI) twice daily, bismuth (~300mg four times daily), metronidazole (500mg three times daily), and tetracycline (500mg four times daily). 1, 2, 3
Why Bismuth Quadruple Therapy?
BQT is recommended as the preferred first-line regimen because it avoids clarithromycin entirely and maintains high eradication rates despite antibiotic resistance patterns, which is the most important factor responsible for eradication failure 1, 2, 3
This regimen is particularly appropriate in high clarithromycin resistance areas (>15%), which now includes most of North America 1, 3, 4
The American College of Gastroenterology and American Gastroenterological Association both endorse this as the preferred empiric first-line treatment when antibiotic susceptibility is unknown 1, 2, 5
Critical Treatment Principles
A 14-day treatment duration is mandatory and superior to 7 days, significantly improving eradication rates regardless of the regimen chosen 1, 2, 3
High-dose PPI (twice daily) increases eradication success by approximately 5% compared to standard dosing and should be used in all regimens 1, 2, 3
Standard PPI doses are: pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, or rabeprazole 20mg, all given twice daily 1
Patient adherence is crucial—incomplete treatment leads to antibiotic resistance and treatment failure 1, 2, 3
Alternative First-Line Regimens (When BQT Unavailable)
In low clarithromycin resistance areas (<15%), PPI-clarithromycin-amoxicillin triple therapy for 14 days can be used, though this is increasingly rare in North America 1, 4
The FDA-approved triple therapy regimen consists of: amoxicillin 1 gram, clarithromycin 500mg, and lansoprazole 30mg, all given twice daily for 14 days 6
Second-Line Treatment After First-Line Failure
After failure of initial therapy, optimized bismuth quadruple therapy for 14 days is the preferred second-line regimen if BQT was not used previously 1, 2, 3
Levofloxacin-containing triple therapy for 14 days is an alternative second-line option (levofloxacin 500mg once daily, amoxicillin 1g twice daily, and PPI twice daily), though rising levofloxacin resistance rates must be considered 1, 2, 5
Rifabutin triple therapy for 14 days is a suitable empiric alternative in patients previously treated with optimized BQT 5
Confirmation of Eradication (Test-of-Cure)
All patients should undergo test-of-cure at least 4 weeks after completing treatment to ensure successful eradication and prevent complications. 1, 2, 3
Testing Methods
Preferred non-invasive testing methods include urea breath test (88-95% sensitivity, 95-100% specificity) or laboratory-based validated monoclonal stool antigen test (>90% sensitivity and specificity) 2
PPIs must be discontinued at least 2 weeks before testing to avoid false-negative results 1, 2, 3
Antibiotics and bismuth must also be discontinued within specified washout periods before testing 1, 2, 3
Special Populations
Penicillin Allergy
In patients with penicillin allergy, bismuth-containing quadruple therapy is recommended in high clarithromycin resistance areas 1, 3
In low clarithromycin resistance areas, PPI-clarithromycin-metronidazole combination for 14 days can be used 1, 3
The FDA-approved dual therapy with amoxicillin and lansoprazole is indicated for patients allergic or intolerant to clarithromycin, but this requires three-times-daily dosing (amoxicillin 1g and lansoprazole 30mg every 8 hours for 14 days) 6
Pediatric Patients
H. pylori treatment in children should 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 should not be used 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
Clinical Context and Indications
When to Test and Treat
Patients under 45-55 years without alarm symptoms should be tested for H. pylori non-invasively and treated if positive ("test and treat" strategy) 7, 3
All patients with confirmed H. pylori infection should be offered eradication therapy 7
Testing and treatment is strongly recommended in patients with active or past peptic ulcer disease, as eradication reduces ulcer recurrence risk by >90% 2, 4
High-Risk Populations Requiring Confirmation of Eradication
Patients with increased risk of gastric cancer must have successful eradication confirmed 7
Patients with low-grade gastric MALT lymphoma require eradication as primary therapy, with mandatory confirmation of successful eradication 2
Patients with bleeding peptic ulcer should start eradication therapy after 72-96 hours of intravenous PPI administration to prevent recurrent bleeding 2
Key Clinical Pitfalls to Avoid
Never perform H. pylori testing while a patient is taking PPIs, antibiotics, or bismuth within the specified washout periods, as bacterial suppression will yield false-negative results. 1, 2, 3
Antibiotic resistance is the most important factor responsible for eradication failure—local surveillance of resistance patterns is mandatory for optimal treatment selection 1, 2, 3
Ensure patients understand the importance of completing the full 14-day course, as incomplete treatment leads to resistance and treatment failure 1, 2, 3
Avoid monotherapy or inappropriate regimens to minimize development of antibiotic resistance 3
Do not use 7-day regimens, as they are inferior to 14-day treatment 1, 2, 3
Residual Symptoms After Successful Eradication
Many patients will have residual dyspeptic symptoms after successful H. pylori eradication, particularly those with functional dyspepsia 7
The primary benefit of eradication is elimination of peptic ulcer mortality risk and prevention of gastric cancer, not necessarily symptom resolution 7
Residual symptoms should be managed with empirical acid suppression therapy (PPIs) if epigastric pain predominates, as these are efficacious for functional dyspepsia 7
Full dose PPI therapy (e.g., omeprazole 20mg once daily) should be first-line for ulcer-like dyspepsia symptoms 7