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

Treatment for H. pylori Infection

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

First-Line Treatment Selection

The choice of first-line therapy depends primarily on local clarithromycin resistance patterns, though bismuth quadruple therapy is now preferred universally due to rising global resistance:

Preferred First-Line Regimen (Universal)

• Bismuth quadruple therapy achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, making it the most reliable empiric choice. 1
• The regimen consists of: PPI (standard dose twice daily), bismuth subsalicylate (~300 mg four times daily), metronidazole (500 mg three to four times daily), and tetracycline (500 mg four times daily) for 14 days. 1
• Bismuth has no described bacterial resistance, and tetracycline resistance remains rare (<5%), making this regimen highly effective even against multi-drug resistant strains. 1

Alternative First-Line Options

• In areas with documented low clarithromycin resistance (<15%), triple therapy with PPI twice daily, clarithromycin 500 mg twice daily, and amoxicillin 1000 mg twice daily for 14 days may be considered. 1, 2
• However, clarithromycin resistance now exceeds 15% in most regions of North America and Europe, making this option increasingly obsolete. 1
• Concomitant non-bismuth quadruple therapy (PPI twice daily + amoxicillin 1000 mg twice daily + clarithromycin 500 mg twice daily + metronidazole 500 mg twice daily for 14 days) is an alternative when bismuth is unavailable. 1

Critical Optimization Factors

Treatment Duration

• 14 days of treatment is mandatory and superior to shorter durations, improving eradication success by approximately 5% compared to 7-10 day regimens. 1

PPI Dosing

• High-dose PPI twice daily is mandatory—standard once-daily dosing is inadequate. 1
• Take PPI 30 minutes before meals on an empty stomach, without concomitant use of other antacids. 1
• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by 8-12% compared to other PPIs. 1

Medication Timing

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

Second-Line Treatment After First-Line Failure

If Bismuth Quadruple Therapy Was Not Used First-Line

• Use bismuth quadruple therapy for 14 days as the second-line option. 1

If Bismuth Quadruple Therapy Failed

• Levofloxacin-based triple therapy (PPI twice daily + amoxicillin 1000 mg twice daily + levofloxacin 500 mg once daily or 250 mg twice daily) for 14 days is the preferred second-line option, provided the patient has no prior fluoroquinolone exposure. 1, 4
• Levofloxacin-based therapy achieves 77-81% eradication rates in intention-to-treat analysis after clarithromycin-based therapy failure. 4
• Do not use levofloxacin if the patient has been previously exposed to any fluoroquinolone antibiotic, as cross-resistance is universal within this class. 1

Third-Line and Rescue Therapies

After Two Failed Eradication Attempts

• Antibiotic susceptibility testing should guide further treatment whenever possible—this is the current standard recommendation. 1
• Molecular testing for clarithromycin and levofloxacin resistance is available and can guide therapy selection earlier in the treatment algorithm. 1

Empiric Rescue Options (When Susceptibility Testing Unavailable)

• Rifabutin-based triple therapy: rifabutin 150 mg twice daily + amoxicillin 1000 mg twice daily + PPI twice daily for 14 days. 1
• Rifabutin resistance is extremely rare, making this an effective rescue option. 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 is an alternative when other options have been exhausted. 1

Special Populations

Patients with Penicillin Allergy

• Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin. 1
• In triple therapy regimens, metronidazole can be substituted for amoxicillin. 1

Pediatric Patients

• Treatment should only be conducted by pediatricians in specialist centers. 1
• First-line options include PPI + amoxicillin + clarithromycin, PPI + amoxicillin + metronidazole, or bismuth + amoxicillin + metronidazole. 1

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

Critical Pitfalls to Avoid

Antibiotic Selection Errors

• Never repeat antibiotics that failed previously, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 1
• When clarithromycin-resistant strains are present, eradication rates drop from 90% to approximately 20%. 1
• Avoid using clarithromycin-containing regimens empirically in areas where clarithromycin resistance exceeds 15-20%—this threshold has been surpassed in most of North America and Europe. 1

Dosing and Duration Errors

• Never use standard-dose PPI once daily—always use twice-daily dosing to maximize gastric pH elevation. 1
• Never use treatment durations shorter than 14 days—this is associated with significantly lower eradication rates. 1

Patient Factors Affecting Success

• Smoking increases the risk of eradication failure with an odds ratio of 1.95. 1
• High BMI, especially in obese patients, increases risk of failure due to lower drug concentrations at the gastric mucosal level. 1
• Poor compliance (>10% of patients) leads to much lower eradication rates—address this proactively. 1

Adjunctive Therapies

Probiotics

• Consider adjunctive probiotics to reduce the risk of antibiotic-associated diarrhea (which occurs in 21-41% of patients) and improve patient compliance. 1
• Probiotics reduce side effects but have no solid evidence to significantly increase eradication rates. 1

Antimicrobial Stewardship Considerations

• Bismuth quadruple therapy 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. 1
• The FDA recommends fluoroquinolones (like levofloxacin) be used as a last choice due to risk of serious side effects. 1