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

Recommended Treatment for H. pylori Infection

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

First-Line Treatment Selection

The choice of first-line therapy depends critically on local clarithromycin resistance patterns:

In Areas with High Clarithromycin Resistance (≥15%)

• Use bismuth quadruple therapy for 14 days as the preferred first-line regimen, which achieves eradication rates of 80-90% even against metronidazole-resistant strains due to bismuth's synergistic effects. 1
• This regimen is particularly valuable because bacterial resistance to bismuth is extremely rare, making it effective even when other antibiotics have developed resistance. 1
• The World Health Organization has identified H. pylori as one of only 12 bacterial species requiring urgent investment in new antibiotics due to high clarithromycin resistance rates exceeding 15% in most North American regions. 1

When Bismuth is Unavailable

• Concomitant non-bismuth quadruple therapy is the recommended alternative: PPI twice daily + amoxicillin 1000 mg twice daily + metronidazole 500 mg twice daily + clarithromycin 500 mg twice daily for 14 days. 1
• This regimen should only be used when bismuth-based therapy cannot be obtained, as it contributes more significantly to global antibiotic resistance. 1

In Areas with Low Clarithromycin Resistance (<15%)

• Triple therapy may be considered: PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1 g twice daily for 14 days. 1, 2
• However, given the global trend of increasing clarithromycin resistance, bismuth quadruple therapy remains the safer first-line choice even in low-resistance areas. 1

Critical Treatment Optimization Strategies

Dosing and Duration

• Always use high-dose PPI twice daily (not once daily) to reduce gastric acidity and enhance antibiotic activity, which significantly increases eradication success. 1, 2
• Treat for 14 days, not 7-10 days, as extending treatment duration improves eradication success by approximately 5%. 1, 2
• For bismuth quadruple therapy, higher doses of metronidazole (1.5-2 g daily in divided doses) improve eradication rates even with resistant strains. 1

Administration Timing

• Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance. 3

Antibiotic Selection Principles

• Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as resistance is likely to have developed. 1, 2
• Clarithromycin resistance dramatically reduces treatment success rates from approximately 90% to 20%. 2
• Amoxicillin and tetracycline resistance rates remain low at 1-5%, making them reliable choices. 1

Second-Line Treatment After First-Line Failure

• Levofloxacin-based triple therapy is the recommended second-line option: PPI twice daily + amoxicillin 1 g twice daily + levofloxacin 500 mg twice daily for 10-14 days. 1, 4
• This regimen achieves 75-81% eradication rates in patients who failed first-line therapy. 5, 6
• Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates and FDA warnings about serious side effects. 1
• If bismuth quadruple therapy was not used as first-line, it can be used as second-line treatment. 1, 4

Third-Line and Rescue Therapies

• After two failed eradication attempts, antibiotic susceptibility testing is mandatory to guide further treatment. 1, 2, 4
• If susceptibility testing is unavailable, use antibiotics not previously used or for which resistance is unlikely: amoxicillin, tetracycline, bismuth, or furazolidone. 4
• Rifabutin-based triple therapy (rifabutin 150 mg twice daily + amoxicillin + PPI) for 14 days is an acceptable rescue option, as rifabutin resistance is extremely rare. 1
• High-dose dual therapy with amoxicillin and PPI is an alternative rescue option. 1

Confirming Eradication

• Confirm eradication with urea breath test or monoclonal stool antigen test at least 4 weeks after completion of therapy and at least 2 weeks after PPI discontinuation. 1, 2
• This timing is critical to avoid false-negative results from residual PPI effects or incomplete bacterial clearance.

Managing Side Effects and Compliance

• Diarrhea occurs in 21-41% of patients during the first week due to disruption of normal gut microbiota. 1
• Consider adjunctive probiotics to reduce the risk of diarrhea and improve patient compliance. 1, 2, 4
• Adverse effects with levofloxacin-based therapy are generally mild (nausea 8%, metallic taste 5%, abdominal pain 3%, myalgias 3%) and rarely require discontinuation. 6

Common Pitfalls to Avoid

• Do not use 7-day treatment regimens—they are outdated and achieve significantly lower eradication rates than 14-day courses. 1, 2
• Do not use standard triple therapy empirically in most regions, as clarithromycin resistance now exceeds 15% in most of North America and Europe. 1, 2
• Do not assume penicillin allergy without verification—consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare. 1
• Do not use once-daily PPI dosing—twice-daily dosing is essential for adequate acid suppression and antibiotic efficacy. 1, 2