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

H. pylori Treatment

Bismuth quadruple therapy for 14 days is the recommended first-line treatment for H. pylori infection, consisting of a high-dose PPI twice daily, bismuth subsalicylate, tetracycline, and metronidazole. 1, 2

First-Line Treatment Regimen

Bismuth quadruple therapy achieves 80-90% eradication rates even against metronidazole-resistant strains due to the synergistic effect of bismuth with other antibiotics. 1, 2 This regimen is preferred because:

• Clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective 2, 3
• Bismuth has no described bacterial resistance, making it highly reliable 2, 3
• The regimen uses antibiotics from the WHO "Access group" (tetracycline and metronidazole) rather than the "Watch group" (clarithromycin, levofloxacin), making it preferable from an antimicrobial stewardship perspective 3

Specific Dosing for Bismuth Quadruple Therapy

• PPI (esomeprazole or rabeprazole 40 mg) twice daily, taken 30 minutes before meals 3, 4
• Bismuth subsalicylate 262 mg or bismuth subcitrate 120 mg four times daily 2
• Metronidazole 500 mg three to four times daily (total 1.5-2 g daily) 3
• Tetracycline 500 mg four times daily 3
• Duration: 14 days 1, 2, 3

Alternative First-Line Option When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth is not available. 3 This consists of:

• PPI twice daily 3
• Amoxicillin 1000 mg twice daily 3, 4
• Clarithromycin 500 mg twice daily 3
• Metronidazole 500 mg twice daily 3

This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing the development of resistance during treatment. 3

Critical Optimization Factors

PPI Dosing is Crucial

• High-dose PPI (twice daily) is mandatory and increases eradication efficacy by 6-10% compared to standard doses 1, 2
• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by 8-12% 3
• Standard-dose PPI once daily is inadequate—always use twice-daily dosing to maximize gastric pH elevation 3
• Take PPI 30 minutes before meals on an empty stomach, without concomitant use of other antacids 3

Treatment Duration Matters

• 14-day duration is superior to 7-10 day regimens, improving eradication success by approximately 5% 1, 2, 3
• The 14-day duration is preferred to maximize eradication rates on the first attempt 1, 3

Second-Line Treatment After First-Line Failure

After failure of first-line therapy, choose between bismuth quadruple therapy (if not previously used) or levofloxacin triple therapy for 14 days. 1, 2

Levofloxacin Triple Therapy

• PPI twice daily 1, 3
• Amoxicillin 1000 mg twice daily 1, 3, 4
• Levofloxacin 500 mg once daily or 250 mg twice daily 1, 3
• Duration: 14 days 1

Important caveat: Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates (11-30% primary, 19-30% secondary). 1, 3

Third-Line and Rescue Therapies

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

Rifabutin Triple Therapy

Rifabutin triple therapy for 14 days is highly effective for persistent infection after multiple failures, with rare bacterial resistance to rifabutin. 1, 3

• Rifabutin 150 mg twice daily 3
• Amoxicillin 1000 mg twice daily 3, 4
• PPI twice daily 3
• Duration: 14 days 1

High-Dose Dual Therapy

• Amoxicillin 2-3 grams daily in 3-4 split doses 3, 4
• High-dose PPI twice daily 3
• Duration: 14 days 3

This is reserved for when other options have been exhausted. 3

When Susceptibility Testing is Not Available

Treatment should be based on prior antibiotic exposure, avoiding previously used antibiotics, especially clarithromycin and levofloxacin. 1, 2

• Never repeat clarithromycin if the patient has prior macrolide exposure (for any indication), as cross-resistance is universal within the macrolide family 3
• Amoxicillin and tetracycline can be re-used because resistance to these agents remains rare 2
• Metronidazole can be re-used with bismuth because bismuth's synergistic effect overcomes in vitro resistance 2

Verification of 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

• Never use serology to confirm eradication—antibodies may persist long after successful treatment 1, 2

Special Populations

Penicillin Allergy

Bismuth quadruple therapy is the first choice in patients with penicillin allergy, as it contains tetracycline, not amoxicillin. 2, 3

Pediatric Patients

• Treatment of H. pylori infection in pediatric patients should only be conducted by pediatricians in specialist centers 3
• Fluoroquinolones and tetracyclines should not be used in children 2
• First-line options include PPI + amoxicillin + clarithromycin, PPI + amoxicillin + metronidazole, or bismuth + amoxicillin + metronidazole 2

Critical Pitfalls to Avoid

Antibiotic Resistance Patterns

• When H. pylori strains are clarithromycin-resistant, eradication rates drop to approximately 20% compared to 90% with susceptible strains 3
• Clarithromycin resistance has increased globally from 9% in 1998 to 17.6% in 2008-2009, making traditional triple therapy achieve only 70% eradication rates in many regions—well below the 80% minimum target 3
• Standard triple therapy regimen should be abandoned when regional clarithromycin resistance exceeds 15-20% 2, 3

Patient Compliance and Factors Affecting Success

• More than 10% of patients are poor compliers, leading to much lower eradication rates—address compliance issues proactively 3
• Smoking increases the risk of eradication failure (odds ratio 1.95) 3
• High BMI, especially in obese patients, increases risk of failure due to lower drug concentrations at the gastric mucosal level 3

Medication Administration

• Confirm that patients are taking the PPI correctly (30 minutes before meals on an empty stomach) to maximize absorption and activation 1, 3
• Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance 4

Adjunctive Therapy

Probiotics can be used as adjuvant treatment to reduce side effects, particularly antibiotic-associated diarrhea (which occurs in 21-41% of patients), though evidence for increased eradication rates is limited. 2, 3, 5