What is the recommended treatment regimen for a patient with a confirmed diagnosis of Helicobacter pylori (H. pylori) infection?

Treatment of Helicobacter pylori Infection

For treatment-naive patients with confirmed H. pylori infection, bismuth quadruple therapy for 14 days is the preferred first-line regimen, 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

First-Line Treatment Selection

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

In High Clarithromycin Resistance Areas (>15-20%)

• Bismuth quadruple therapy (BQT) for 14 days is the preferred first-line treatment, as it avoids clarithromycin entirely and maintains high eradication rates despite antibiotic resistance patterns 1, 2, 3
• Concomitant therapy (non-bismuth quadruple therapy) for 14 days is an alternative, consisting of PPI twice daily, clarithromycin 500mg twice daily, amoxicillin 1g twice daily, and metronidazole 500mg twice daily 1, 4
• Rifabutin triple therapy for 14 days (rifabutin 150-300mg daily, amoxicillin 1g twice daily, PPI twice daily) is a suitable empiric alternative in patients without penicillin allergy 3

In Low Clarithromycin Resistance Areas (<15%)

• PPI-clarithromycin-amoxicillin triple therapy for 14 days can be used (clarithromycin 500mg twice daily, amoxicillin 1g twice daily, PPI twice daily) 1, 2
• BQT for 14 days remains an excellent option even in low-resistance areas 1, 4

Critical Dosing Considerations

• High-dose PPI (twice daily) increases eradication success by approximately 5% compared to standard dosing 1, 2
• Standard PPI doses are: pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, rabeprazole 20mg 5
• Treatment duration of 14 days is superior to 7 days and should be standard 1, 2
• PPIs should be dosed 30 minutes before eating on an empty stomach, without concomitant antacids 5

Second-Line Treatment After First-Line Failure

If BQT Was Not Used Previously

• Optimized bismuth quadruple therapy for 14 days is the preferred second-line regimen 5, 3

If BQT Was Used Previously

• Levofloxacin-containing triple therapy for 14 days (levofloxacin 500mg once daily, amoxicillin 1g twice daily, PPI twice daily) is an alternative, though rising levofloxacin resistance rates must be considered 5, 2
• Rifabutin triple therapy for 14 days is suitable for patients who have failed previous treatments 3

Third-Line Treatment and Refractory Infection

• After two failed therapies with confirmed patient adherence, H. pylori susceptibility testing should be performed to guide subsequent regimens 5
• If susceptibility testing is unavailable, use antibiotics not previously used or for which resistance is unlikely (amoxicillin, tetracycline, bismuth, furazolidone) 4
• High-dose dual therapy (amoxicillin 2-3g daily in 3-4 split doses, high-dose PPI twice daily for 14 days) is an option after sensitivity testing 5

Special Populations

Patients with Penicillin Allergy

• In low clarithromycin resistance areas: PPI-clarithromycin-metronidazole combination for 14 days 1, 2
• In high clarithromycin resistance areas: bismuth-containing quadruple therapy (which does not contain penicillin) 1, 2

FDA-Approved Regimens for H. pylori and Duodenal Ulcer

• Triple therapy: amoxicillin 1g, clarithromycin 500mg, and lansoprazole 30mg, all given twice daily for 14 days 6
• Dual therapy: amoxicillin 1g and lansoprazole 30mg, given three times daily for 14 days 6

Confirmation of Eradication

• All patients should undergo test-of-cure at least 4 weeks after completing treatment 1, 2, 3
• Urea breath test or laboratory-based validated monoclonal stool antigen test are the preferred non-invasive methods 1, 2
• PPIs must be discontinued at least 2 weeks before testing to avoid false-negative results 1, 2
• Sucralfate must be discontinued at least 4 weeks before testing 2
• Antibiotics must be discontinued at least 4 weeks before testing 2

Key Clinical Pitfalls to Avoid

• Never perform H. pylori testing while a patient is taking PPIs, antibiotics, or sucralfate within the specified washout periods, as bacterial suppression will yield false-negative results 1, 2
• Antibiotic resistance is the most important factor responsible for eradication failure—local surveillance of resistance patterns is mandatory for optimal treatment selection 1, 2, 4
• Avoid monotherapy or inappropriate regimens to minimize development of antibiotic resistance 5, 1
• Patient compliance is crucial—ensure patients understand the importance of completing the full 14-day course, as incomplete treatment leads to resistance and treatment failure 1, 2
• Never use clarithromycin or levofloxacin in salvage regimens unless antibiotic susceptibility is confirmed 3

Indications for H. pylori Eradication

• Active or history of peptic ulcer disease 2, 4, 7
• Gastric MALT lymphoma 2, 4
• First-degree relatives of patients with gastric cancer 2, 4
• Previous gastric neoplasia treated by endoscopic or subtotal gastric resection 2
• Chronic NSAID or aspirin use 4, 7
• Iron deficiency anemia, idiopathic thrombocytopenic purpura, or vitamin B12 deficiency 4

Who to Test

• Patients under 45-55 years without alarm symptoms should be tested for H. pylori non-invasively and treated if positive 1
• Patients over 45-55 years with new dyspeptic symptoms or any patient with alarm symptoms should be referred for endoscopy 1