What is the recommended treatment for eradication of Helicobacter pylori (H. pylori) infection?

H. pylori Eradication Treatment

Bismuth-containing quadruple therapy for 14 days is the preferred first-line treatment for H. pylori eradication in most clinical settings, particularly in areas with high clarithromycin resistance (>15-20%). 1

First-Line Treatment Selection

The choice of initial eradication regimen depends critically on local clarithromycin resistance rates:

High Clarithromycin Resistance Areas (>15-20%)

• Bismuth quadruple therapy for 14 days is the standard of care, consisting of a proton pump inhibitor (PPI) + bismuth + tetracycline + metronidazole 1
• This regimen achieves eradication rates exceeding 80% even in areas with high antibiotic resistance 2, 1
• High-dose PPI (rabeprazole 40 mg or esomeprazole 40 mg twice daily) should be used rather than pantoprazole to optimize acid suppression 1

Low Clarithromycin Resistance Areas (<15%)

• PPI-clarithromycin-amoxicillin triple therapy for 14 days can be used as an alternative 1
• PPI-clarithromycin-metronidazole triple therapy for 14 days is another option 1
• Extending treatment duration from 7 to 14 days improves eradication success by approximately 5% 1
• The combination of omeprazole plus clarithromycin plus amoxicillin achieved 69-83% eradication rates in intention-to-treat analyses 3

Critical caveat: Triple therapy with clarithromycin should be avoided as monotherapy or in inappropriate regimens to minimize antibiotic resistance development 2

Second-Line Treatment After First-Line Failure

After PPI-Clarithromycin Triple Therapy Failure

• Bismuth-containing quadruple therapy for 14 days is the preferred second-line option if not used initially 1
• Levofloxacin-containing triple therapy for 14 days is an alternative, though rising levofloxacin resistance rates must be considered 1
• Avoid antibiotics used in the first-line regimen to prevent resistance 2, 1

Third-Line Treatment After Multiple Failures

• Antimicrobial susceptibility testing should guide treatment selection whenever possible 1
• Rifabutin triple therapy for 14 days is an option for patients who have failed previous treatments 1
• Use antibiotics not previously administered or to which resistance is unlikely (amoxicillin, tetracycline, bismuth, or furazolidone) 4

Special Populations

Patients with Penicillin Allergy

• In low clarithromycin resistance areas: PPI-clarithromycin-metronidazole combination 1
• In high clarithromycin resistance areas: Bismuth-containing quadruple therapy (which does not contain penicillin) 1

Patients on Long-Term NSAIDs or Aspirin

• H. pylori eradication should be undertaken in patients with a history of peptic ulcers before starting or continuing NSAIDs 2
• Eradication is mandatory in patients with peptic ulcer history before NSAID initiation 2
• The residual risk of peptic ulcer bleeding after successful eradication in aspirin users is very low 2

Confirmation of Eradication

Testing to confirm eradication must be performed at least 4 weeks after completing treatment 2, 1:

Non-Invasive Testing (Preferred for Most Patients)

• Urea breath test (13C-UBT) is the gold standard for non-invasive confirmation 2, 1
• Laboratory-based validated monoclonal stool antigen test is an alternative 1
• Serology should NOT be used for early assessment of eradication success, as antibody titers take up to 6 months to fall by 50% 2

Endoscopy-Based Testing (Required for Specific Conditions)

Mandatory confirmation via endoscopy with biopsy in 2, 1:

• Complicated peptic ulcer disease
• Gastric ulcer (also requires histological assessment to exclude malignancy)
• Low-grade gastric MALT lymphoma
• Any situation requiring histological assessment of mucosal abnormalities

Biopsy protocol: Two specimens from both antrum and body, plus one for rapid urease test 2

Critical Indications for H. pylori Eradication

Strongly recommended indications 2, 1:

• All patients with peptic ulcer disease (active or history)
• Gastric ulcer (eradication achieves >90% healing rates) 2
• Duodenal ulcer (eradication eliminates need for prolonged PPI in uncomplicated cases) 2
• Low-grade gastric MALT lymphoma (first-line treatment) 2
• First-degree relatives of patients with gastric cancer 1
• Patients with previous gastric neoplasia treated endoscopically or by subtotal gastrectomy 1
• Iron-deficiency anemia, idiopathic thrombocytopenic purpura, or vitamin B12 deficiency 2

PPI Management After Eradication

• Uncomplicated duodenal ulcer: Prolonged PPI after eradication is NOT recommended 2
• Gastric ulcer and complicated duodenal ulcer: Continue PPI until complete healing is confirmed 2
• In bleeding ulcers, start eradication therapy when oral feeding is reintroduced 2

Key Factors for Treatment Success

Patient compliance is the most critical factor for successful eradication 2:

• Ensure patients understand the importance of completing the full 14-day course
• Avoid mono-antibiotic therapy, which promotes resistance 2
• Never use antibiotics to which the patient has been previously exposed 1

Antibiotic resistance is the primary reason for eradication failure 1:

• Local surveillance of H. pylori antibiotic resistance patterns is mandatory 1
• Culture and sensitivity testing should be used after second-line treatment failure 2, 1

Important Testing Precautions

Medications that must be discontinued before H. pylori testing 1:

• PPIs: Discontinue at least 2 weeks before testing
• Antibiotics: Discontinue at least 4 weeks before testing
• Sucralfate: Discontinue at least 4 weeks before testing (suppresses but does not eradicate H. pylori, causing false-negative results) 1