What is the first line therapy for H pylori (Helicobacter pylori) infection in adults?

First-Line H. pylori Therapy in Adults

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection in adults, consisting of a PPI twice daily, bismuth subsalicylate, metronidazole, and tetracycline. 1, 2, 3

Recommended First-Line Regimen

Bismuth Quadruple Therapy (14 days):

• PPI (standard dose) twice daily - taken 30 minutes before meals 1, 3
• Bismuth subsalicylate 262 mg (2 tablets) four times daily 1
• Metronidazole 500 mg three to four times daily (total 1.5-2 g daily) 1, 3
• Tetracycline 500 mg four times daily 1, 3

This regimen achieves 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance, because bismuth has no described bacterial resistance and overcomes metronidazole resistance through synergistic effects. 1, 3

Alternative First-Line Option When Bismuth is Unavailable

Concomitant Non-Bismuth Quadruple Therapy (14 days):

• PPI twice daily 1, 3
• Amoxicillin 1000 mg twice daily 1, 3, 4
• Clarithromycin 500 mg twice daily 1, 3
• Metronidazole 500 mg twice daily 1, 3

This regimen should only be used when bismuth is not available, as it administers all antibiotics simultaneously to prevent resistance development during treatment. 1

When Triple Therapy May Be Considered (Restricted Use)

PPI-Clarithromycin-Amoxicillin Triple Therapy may only be considered in areas with documented clarithromycin resistance <15%, which is now rare in most regions. 1, 2, 3 This consists of:

• PPI twice daily 2, 3
• Clarithromycin 500 mg twice daily 2, 3
• Amoxicillin 1000 mg twice daily 2, 3, 4
• Duration: 14 days 2, 3

Critical caveat: Standard triple therapy should be abandoned when regional clarithromycin resistance exceeds 15-20%, as eradication rates drop from 90% with susceptible strains to approximately 20% with resistant strains. 1, 2 Clarithromycin resistance has increased globally from 9% in 1998 to 17.6% in 2008-2009, and now exceeds 20% in most of North America and Central, Western, and Southern Europe. 1

Critical Optimization Factors

PPI Dosing

• Always use high-dose PPI twice daily (not standard once-daily dosing), which increases cure rates by 6-10% compared to standard dosing. 1, 2, 3
• Esomeprazole or rabeprazole 40 mg twice daily may increase cure rates by an additional 8-12% compared to other PPIs. 1, 2
• Take 30 minutes before meals on an empty stomach, without concomitant antacids. 1

Treatment Duration

• 14 days is mandatory for all regimens, improving eradication success by approximately 5% compared to 7-10 day regimens. 1, 2, 3, 5

Antibiotic Selection

• Avoid repeating antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin, as resistance develops rapidly after exposure. 1, 2, 3
• Never assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates. 1

Special Populations

Penicillin Allergy

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

H. pylori Dosing per FDA Label

For H. pylori infection specifically, the FDA-approved dosing for amoxicillin is 1 gram twice daily (every 12 hours) for 14 days when used in triple therapy with clarithromycin and lansoprazole. 4

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, 3
• Never use serology to confirm eradication—antibodies may persist long after successful treatment. 1, 3

Common Pitfalls to Avoid

• Inadequate PPI dosing (once daily or standard doses) significantly reduces efficacy—always use twice-daily high-dose PPI. 1, 2, 3
• Using clarithromycin-based triple therapy in areas with resistance >15% results in unacceptably low eradication rates. 1, 2, 3
• Repeating previously failed antibiotics, particularly clarithromycin or levofloxacin, dramatically reduces success rates. 1, 2, 3
• Shorter treatment durations (<14 days) compromise eradication rates. 1, 2, 3, 5
• Standard-dose PPI once daily is inadequate—this is a critical error that significantly reduces treatment success. 1

Patient Factors Affecting Success

• Smoking increases risk of eradication failure (odds ratio 1.95). 1
• High BMI/obesity increases failure risk due to lower drug concentrations at the gastric mucosal level. 1
• Poor compliance (>10% of patients) leads to much lower eradication rates—counsel patients on the importance of completing the full 14-day course. 1

Adjunctive Therapy

• Consider probiotics to reduce antibiotic-associated diarrhea (occurs in 21-41% of patients during the first week) and improve compliance, though evidence for increasing eradication rates is limited. 1, 2, 3