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

H. pylori Treatment

First-Line Treatment Recommendation

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection, consisting of a high-dose PPI twice daily, bismuth subsalicylate (262 mg, 2 tablets four times daily), metronidazole (500 mg three to four times daily), and tetracycline (500 mg four times daily). 1, 2

Why Bismuth Quadruple Therapy is Preferred

• This regimen achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it superior to traditional triple therapy which now fails in over 30% of cases due to rising antibiotic resistance 1, 2
• Bacterial resistance to bismuth is extremely rare, and the synergistic effect of bismuth overcomes metronidazole resistance even when present 1, 2, 3
• Clarithromycin resistance now exceeds 15% in most regions of North America and Europe, making traditional triple therapy unacceptably ineffective 2, 3

Critical Optimization Factors

• Use high-dose PPI twice daily (not standard dosing) - this increases eradication efficacy by 6-10% by reducing gastric acidity and enhancing antibiotic activity 1, 2
• Esomeprazole or rabeprazole 40 mg twice daily are preferred over other PPIs as they increase cure rates by an additional 8-12% 1, 2
• Take PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1, 2
• 14-day duration is mandatory - this improves eradication success by approximately 5% compared to 7-10 day regimens 1, 2, 4

Alternative First-Line Option When Bismuth is Unavailable

Concomitant non-bismuth quadruple therapy for 14 days consisting of PPI twice daily, amoxicillin 1000 mg twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg twice daily 2, 3

• This regimen administers all antibiotics simultaneously, preventing resistance development during treatment 2
• Only use this option when bismuth is truly unavailable, as bismuth quadruple therapy has superior resistance profiles 1, 2

Triple Therapy: Restricted Use Only

• PPI + clarithromycin + amoxicillin for 14 days should only be used in areas with documented clarithromycin resistance below 15% 2, 3
• This regimen is no longer recommended as first-line in most regions due to rising clarithromycin resistance rates 2, 3
• When clarithromycin-resistant strains are present, eradication rates drop from 90% to approximately 20% 2

Second-Line Treatment After First-Line Failure

If Bismuth Quadruple Therapy Was Used First

• Levofloxacin triple therapy for 14 days: PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily (or 250 mg twice daily) 1, 2
• Only use if patient has no prior fluoroquinolone exposure, as resistance rates are rising (11-30% primary, 19-30% secondary) 1, 2

If Clarithromycin-Based Therapy Was Used First

• Bismuth quadruple therapy for 14 days (if not previously used) 1, 2
• This is highly effective as a rescue option due to rare bismuth resistance 1, 2

Critical Principle for Second-Line Therapy

• Never repeat antibiotics that failed previously - especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure 1, 2

Third-Line and Rescue Therapies

After Two Failed Eradication Attempts

• Antibiotic susceptibility testing should guide further treatment whenever possible 1, 2, 5
• When susceptibility testing is unavailable, treatment should be based on prior antibiotic exposure, avoiding previously used antibiotics 1

Rifabutin Triple Therapy

• Rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily for 14 days 1, 2
• Rifabutin resistance is extremely rare, making this an effective rescue option after multiple treatment failures 1, 2
• Reserve this regimen for patients who have failed at least 2-3 prior treatment attempts 1

High-Dose Dual Amoxicillin-PPI Therapy

• Amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily for 14 days 1
• This is an alternative rescue therapy when other options have been exhausted 1

Special Populations

Penicillin Allergy

• Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin 2, 3
• Consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as amoxicillin resistance remains rare (<5%) 1

Pediatric Patients

• 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
• Treatment should only be conducted by pediatricians in specialist centers 2

H. pylori with Duodenal Ulcer Disease (FDA-Approved Regimens)

• Triple therapy: 1 gram amoxicillin + 500 mg clarithromycin + 30 mg lansoprazole, all given twice daily for 14 days 6
• Dual therapy (for clarithromycin-allergic or intolerant patients): 1 gram amoxicillin + 30 mg lansoprazole, each given three times daily for 14 days 6

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

Common Pitfalls and How to Avoid Them

Inadequate PPI Dosing

• Standard once-daily PPI dosing is inadequate and significantly reduces treatment efficacy 1, 2
• Always use high-dose PPI twice daily (e.g., esomeprazole or rabeprazole 40 mg twice daily) 1, 2

Assuming Low Clarithromycin Resistance

• Never assume low clarithromycin resistance without local surveillance data - most regions now have resistance rates exceeding 15-20% 2, 3
• Avoid PPI-clarithromycin triple therapy as first-line unless you have documented local resistance data showing <15% resistance 2, 3

Repeating Failed Antibiotics

• Avoid repeating clarithromycin if the patient has prior macrolide exposure for any indication, as cross-resistance is universal within the macrolide family 2
• Do not use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates 1, 2

Inadequate Treatment Duration

• 7-10 day regimens are no longer acceptable - always use 14-day treatment duration to maximize eradication rates 1, 2, 4

Poor Patient Compliance

• More than 10% of patients are poor compliers, leading to much lower eradication rates 2
• Address compliance issues proactively by explaining the importance of completing the full course and taking medications at the start of meals to minimize gastrointestinal intolerance 6

Patient Factors Affecting Success

• Smoking increases the risk of eradication failure (odds ratio 1.95) 2
• High BMI, especially in obese patients, increases risk of failure due to lower drug concentrations at the gastric mucosal level 2

Adjunctive Therapies

• Probiotics can be used as adjunctive 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
• The primary focus should be on optimizing the antibiotic regimen, not on functional supplementation 2