Treatment for H. pylori Infection
Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a proton pump inhibitor (PPI) twice daily, bismuth, metronidazole, and tetracycline. 1, 2, 3
First-Line Treatment Regimens
Bismuth quadruple therapy is strongly recommended as the preferred empirical first-line treatment, particularly in areas with high clarithromycin resistance (>15-20%), which includes most of North America. 4, 1, 2 This regimen avoids clarithromycin entirely and maintains high eradication rates despite antibiotic resistance patterns. 2
The standard bismuth quadruple therapy consists of:
- PPI twice daily (pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, or rabeprazole 20mg) 2
- Bismuth subsalicylate
- Metronidazole 500mg twice daily 4
- Tetracycline 500mg four times daily 4
- Duration: 14 days 4, 1, 2, 3
Alternative First-Line Options
In areas with documented low clarithromycin resistance (<15%), PPI-clarithromycin-amoxicillin triple therapy for 14 days can be used, though this is increasingly rare in North America. 1, 2 The triple therapy regimen includes:
High-dose PPI (twice daily) is critical, as it increases eradication success by approximately 5% compared to standard dosing. 1, 2 Rabeprazole 40mg or esomeprazole 40mg twice daily are preferred over pantoprazole for optimal results. 1
Concomitant non-bismuth quadruple therapy (PPI + amoxicillin + metronidazole + clarithromycin) for 14 days is appropriate in high clarithromycin resistance areas where bismuth is not available. 4
For Patients with Penicillin Allergy
In patients with penicillin allergy, bismuth-containing quadruple therapy remains the preferred regimen in high clarithromycin resistance areas. 1, 2 In low clarithromycin resistance areas, PPI-clarithromycin-metronidazole combination for 14 days can be used. 1, 2
Second-Line Treatment After First-Line Failure
After failure of first-line therapy, optimized bismuth quadruple therapy for 14 days is the preferred second-line regimen for patients who have not previously received optimized bismuth therapy and for whom antibiotic susceptibility is unknown. 4, 3
Levofloxacin-containing triple therapy for 14 days is an alternative second-line option, though rising levofloxacin resistance rates (now significant in many regions) must be considered. 4, 1, 2 Levofloxacin-based regimens should only be used if local resistance rates are low or susceptibility is confirmed. 4, 3
The key principle for second-line therapy is to avoid antibiotics used in the first-line regimen, as the bacterium may have developed resistance. 4
Third-Line and Salvage Therapy
After failure of second-line therapy, treatment should be guided by antimicrobial susceptibility testing whenever possible. 1, 3 Culture and sensitivity testing should be used to ensure choice of appropriate antimicrobial therapy. 4
Rifabutin triple therapy for 14 days is an option for patients who have failed previous treatments, consisting of PPI, amoxicillin, and rifabutin. 1, 3 This is particularly useful when other regimens have failed and susceptibility testing is not available.
Salvage regimens containing clarithromycin or levofloxacin should only be used if antibiotic susceptibility is confirmed, as resistance to these antibiotics is the most important factor responsible for treatment failure. 4, 3
Confirmation of Eradication (Test-of-Cure)
All patients must undergo test-of-cure at least 4 weeks after completing treatment. 1, 2, 6 This timing is critical because testing earlier may yield false-negative results due to bacterial suppression rather than true eradication. 6
The urea breath test (UBT) or laboratory-based validated monoclonal stool antigen test are the recommended non-invasive tests for confirming eradication. 1, 2
Critical Testing Pitfalls to Avoid
PPIs must be discontinued at least 2 weeks before testing to avoid false-negative results. 2 Similarly, sucralfate must be discontinued at least 4 weeks before H. pylori testing, as it can suppress but not eradicate the bacteria. 1
Never perform H. pylori testing while a patient is taking PPIs, antibiotics, or sucralfate within the specified washout periods, as bacterial suppression will yield unreliable results and may lead to missed diagnoses. 1, 2
Endoscopy-based testing is necessary for patients with complicated peptic ulcer disease, gastric ulcer, and MALT lymphoma, using biopsy specimens from both the antrum and body. 4, 1 In gastric ulcer cases, histological examination should also be performed to exclude malignancy, as some gastric malignancies can only be detected during or following the healing process. 4
Key Clinical Considerations
Antibiotic resistance is the most important factor responsible for the falling success rate of H. pylori eradication treatment. 4, 1, 2 Local surveillance of H. pylori antibiotic resistance is mandatory, and the antibiotic combination should be chosen according to local resistance patterns. 4
Patient compliance is crucial for successful eradication—ensure patients understand the importance of completing the full 14-day course, as incomplete treatment leads to resistance and treatment failure. 4, 2 The risk of antibiotic resistance is minimized by avoiding inappropriate regimens such as mono-antibiotic therapy and by ensuring high patient compliance. 4
The best approach is to succeed on the first attempt, thus avoiding retreating and retesting, and reducing cost, anxiety, and negative impacts on other gut microbiota. 4
Amoxicillin should be taken at the start of a meal to minimize the potential for gastrointestinal intolerance. 5
Indications for H. pylori Eradication
Eradication is recommended for all patients with peptic ulcer disease (active or history). 1, 3 Non-recurrence of gastric and duodenal ulcer is strictly dependent on the success of H. pylori eradication, and persistence of infection is a negative prognostic marker for ulcer complications such as bleeding. 4
First-degree relatives of family members with gastric cancer should undergo eradication, as they have a two to three times increased risk of developing gastric cancer. 4, 1
Patients with previous gastric neoplasia treated by endoscopic or subtotal gastric resection, severe pan-gastritis, corpus-predominant gastritis, or severe atrophy should be considered for eradication. 4, 1 H. pylori eradication for gastric cancer prevention is most effective before the development of gastric atrophy and should be undertaken in populations at high risk. 4