What is the recommended treatment for H. Pylori (Helicobacter pylori) management?

H. Pylori Management

First-Line Treatment Recommendation

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection in most clinical settings, consisting of a PPI twice daily, bismuth subsalicylate or subcitrate, metronidazole, and tetracycline. 1, 2, 3

This recommendation is based on:

• Eradication rates of 80-90% even against metronidazole-resistant strains due to bismuth's synergistic effect 1
• Clarithromycin resistance now exceeds 15% in most regions of North America and Europe, making traditional triple therapy unacceptably ineffective 1, 2
• No bacterial resistance to bismuth has been described, and tetracycline resistance remains rare 1

Specific Dosing Regimen

Bismuth Quadruple Therapy (14 days): 1, 2

• PPI: Twice daily, 30 minutes before meals (esomeprazole or rabeprazole 40 mg preferred for 8-12% higher cure rates) 1, 2
• Bismuth subsalicylate: 262 mg four times daily OR bismuth subcitrate 120 mg four times daily 1
• Metronidazole: 500 mg three to four times daily (total 1.5-2 g daily) 1
• Tetracycline: 500 mg four times daily 1

Alternative First-Line Options

When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days: 1, 2

• PPI twice daily
• Amoxicillin 1000 mg twice daily
• Clarithromycin 500 mg twice daily
• Metronidazole 500 mg twice daily

This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing resistance development during treatment. 1

In Regions with Low Clarithromycin Resistance (<15%)

Triple therapy for 14 days may be considered: 4, 2

• PPI twice daily
• Clarithromycin 500 mg twice daily
• Amoxicillin 1000 mg twice daily

Critical caveat: Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates. 1

For Penicillin Allergy

Bismuth quadruple therapy is the first choice as it contains tetracycline, not amoxicillin. 1, 2

Second-Line Treatment After First-Line Failure

If bismuth quadruple therapy was not used first-line, use it as second-line for 14 days. 1, 2

If bismuth quadruple therapy has already been used, levofloxacin triple therapy for 14 days: 1, 2

• PPI twice daily
• Amoxicillin 1000 mg twice daily
• Levofloxacin 500 mg once daily or 250 mg twice daily

Important considerations:

• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 1, 2
• Rising levofloxacin resistance rates (11-30% primary, 19-30% secondary) make empiric use problematic 1

Third-Line and Rescue Therapies

After two failed eradication attempts, antibiotic susceptibility testing should guide further treatment whenever possible. 1, 2, 5

Rifabutin triple therapy for 14 days (when susceptibility testing unavailable): 1, 2

• Rifabutin 150 mg twice daily
• Amoxicillin 1000 mg twice daily
• PPI twice daily

Alternative rescue option: High-dose dual amoxicillin-PPI therapy for 14 days: 1

• Amoxicillin 2-3 grams daily in 3-4 divided doses
• High-dose PPI twice daily

Critical Optimization Factors

Treatment Duration

Always prescribe 14 days of treatment—this improves eradication success by approximately 5% compared to 7-10 day regimens. 4, 1, 2

PPI Dosing

High-dose PPI twice daily is mandatory—standard once-daily dosing is inadequate. 1, 2

• Esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8-12% compared to other PPIs 1, 2
• Take 30 minutes before meals on an empty stomach 1

Antibiotic Selection Based on Resistance

Local antibiotic resistance patterns must guide therapy selection, particularly clarithromycin resistance. 4, 1, 2

• When clarithromycin resistance exceeds 15-20%, abandon PPI-clarithromycin triple therapy 4, 1
• Avoid repeating clarithromycin if patient has prior macrolide exposure for any indication—cross-resistance is universal 1

Confirmation of Eradication

Test for eradication success at least 4 weeks after completing therapy using urea breath test or validated monoclonal stool antigen test. 1, 2

Critical timing requirements:

• Discontinue PPI at least 2 weeks before testing 1, 2
• Discontinue sucralfate at least 4 weeks before testing 2
• Never use serology to confirm eradication—antibodies persist long after successful treatment 1

Endoscopy-based testing is necessary for:

• Complicated peptic ulcer disease 4, 2
• Gastric ulcer (to exclude malignancy) 4, 2
• MALT lymphoma 4, 2

Indications for H. Pylori Eradication

Strongly recommended indications: 4, 2

• Active or history of peptic ulcer disease
• Gastric MALT lymphoma
• First-degree relatives of patients with gastric cancer
• Previous gastric neoplasia treated by endoscopic or subtotal gastric resection
• Severe pan-gastritis or corpus-predominant gastritis
• Severe atrophy or intestinal metaplasia
• Chronic NSAID or aspirin use
• Unexplained iron deficiency anemia
• Idiopathic thrombocytopenic purpura

Common Pitfalls to Avoid

Do not use standard triple therapy where clarithromycin resistance exceeds 15%—this is the most common mistake, occurring in 46% of cases. 6

Do not prescribe treatment for only 7-10 days—this occurs in 69% of cases but significantly reduces efficacy. 6

Do not use low-dose PPI once daily—this occurs in 48% of cases and compromises eradication. 6

Do not repeat antibiotics after eradication failure—this occurs in >15% of cases and perpetuates resistance. 6

Do not fail to check eradication success—this occurs in 6% of cases but is essential for confirming cure. 6

Patient Factors Affecting Success

Smoking increases eradication failure risk (odds ratio 1.95). 1

High BMI increases failure risk due to lower drug concentrations at the gastric mucosal level. 1

Poor compliance occurs in >10% of patients—address this proactively with patient education about the importance of completing the full course. 1

Adjunctive Therapies

Consider probiotics to reduce antibiotic-associated diarrhea (occurs in 21-41% of patients during first week) and improve compliance. 1

However, probiotics have no solid evidence to increase eradication rates and should not be considered primary treatment. 1

Special Populations

Pediatric Patients

Treatment should only be conducted by pediatricians in specialist centers. 1

First-line options include: 1

• PPI + amoxicillin + clarithromycin
• PPI + amoxicillin + metronidazole
• Bismuth + amoxicillin + metronidazole

Renal Impairment

Patients with GFR <30 mL/min should NOT receive the 875 mg amoxicillin dose. 7

Dosing adjustments: 7

• GFR 10-30 mL/min: 500 mg or 250 mg every 12 hours
• GFR <10 mL/min: 500 mg or 250 mg every 24 hours
• Hemodialysis: Additional dose during and at end of dialysis

Paradigm Shift in Management

H. pylori gastritis should be treated as an infectious disease with the goal of near-100% cure rates, not as a typical gastroenterological disease with modest success rates. 1

This requires:

• Optimizing the primary antibiotic regimen rather than relying on functional supplementation 1
• Using high-dose PPI twice daily 1
• Extending treatment duration to 14 days 1
• Selecting appropriate antibiotics based on local resistance patterns 1