What is the recommended first‑line regimen for an adult with confirmed Helicobacter pylori infection who has no drug allergies, no prior eradication attempts, and no severe hepatic or renal impairment?

First-Line Treatment for Helicobacter pylori Infection

Bismuth quadruple therapy for 14 days is the definitive first-line treatment for adults with confirmed H. pylori infection who have no drug allergies, no prior eradication attempts, and no severe hepatic or renal impairment, achieving 80–90% eradication rates even in regions with high antibiotic resistance. 1, 2

Recommended Regimen Components

The optimal bismuth quadruple therapy consists of four components taken for 14 days 1, 2, 3:

• Proton-pump inhibitor (PPI): Esomeprazole or rabeprazole 40 mg twice daily is strongly preferred over other PPIs, as it increases cure rates by 8–12% compared with standard-dose PPIs 1, 2
• Bismuth subsalicylate: 262 mg (two tablets) four times daily 1, 2
• Metronidazole: 500 mg three to four times daily (total 1.5–2 g/day) 1, 2
• Tetracycline: 500 mg four times daily 1, 2

Critical Administration Instructions

Proper timing and administration are essential for maximizing efficacy 1, 2:

• Take the PPI 30 minutes before meals on an empty stomach, without concomitant antacids 1, 2
• Take bismuth 30 minutes before meals and at bedtime 2
• Take metronidazole 30 minutes after meals 2
• The 14-day duration is mandatory—extending therapy from 7 to 14 days improves eradication by approximately 5% 1, 2, 3

Why Bismuth Quadruple Therapy Is First-Line

This regimen has become the preferred first-line choice for several compelling reasons 1, 2:

• Clarithromycin resistance now exceeds 15–20% across North America and most of Europe, reducing traditional triple therapy success to only ~70% 1, 2
• Bismuth quadruple therapy is unaffected by clarithromycin resistance and maintains 80–90% eradication even against strains with dual resistance to clarithromycin and metronidazole 1, 2
• No bacterial resistance to bismuth has been reported, and tetracycline resistance remains rare (<5%) 1, 2
• The regimen uses WHO "Access" antibiotics (tetracycline, metronidazole) rather than "Watch" agents (clarithromycin, levofloxacin), supporting antimicrobial stewardship 1

Alternative First-Line Option (When Bismuth Unavailable)

If bismuth is unavailable and local clarithromycin resistance is documented to be <15%, concomitant non-bismuth quadruple therapy may be used 1, 2, 3:

• PPI (esomeprazole or rabeprazole 40 mg) twice daily
• Amoxicillin 1000 mg twice daily
• Clarithromycin 500 mg twice daily
• Metronidazole 500 mg twice daily
• Duration: 14 days 1, 2

However, this option should be avoided in most clinical settings because clarithromycin resistance exceeds 15% in the majority of North America and Europe 1, 2.

Critical Pitfalls to Avoid

Several common errors dramatically reduce eradication success 1, 2:

• Never use once-daily PPI dosing—it is a major cause of treatment failure 1
• Avoid pantoprazole because 40 mg provides acid suppression equivalent to only ~9 mg omeprazole, yielding inferior outcomes 1
• Do not shorten therapy below 14 days—this reduces eradication by ~5% 1, 2, 3
• Do not use clarithromycin-based triple therapy empirically unless local surveillance confirms resistance <15%, which is rare in most regions 1, 2

Expected Side Effects and Patient Counseling

Prepare patients for common adverse effects to improve adherence 4, 1:

• Diarrhea occurs in 21–41% of patients during the first week due to gut microbiota disruption; this does not indicate treatment failure 4, 1
• Adjunctive probiotics may be considered to reduce diarrhea risk and improve compliance 1
• Emphasize the importance of completing the full 14-day course, as poor compliance is a leading cause of failure 1, 2

Patient Factors That Reduce Success

Certain host factors lower eradication rates and should be addressed 1:

• Smoking roughly doubles the odds of treatment failure (OR ≈1.95)—advise cessation during therapy 1
• Elevated BMI/obesity may lower gastric mucosal drug concentrations, potentially reducing efficacy 1

Confirmation of Eradication (Test-of-Cure)

Eradication must be confirmed in all patients 1, 2:

• Perform a urea breath test or monoclonal stool antigen test at least 4 weeks after completing therapy 1, 2
• Discontinue PPI at least 2 weeks before testing to avoid false-negative results 1, 2
• Never use serology for confirmation because antibodies persist long after successful eradication 1

Second-Line Therapy (If First-Line Fails)

If bismuth quadruple therapy fails, the next step depends on prior antibiotic exposure 4, 1, 2:

• Levofloxacin triple therapy for 14 days (PPI + amoxicillin + levofloxacin) is recommended only if the patient has had no prior fluoroquinolone exposure 4, 1, 2
• After two documented treatment failures with confirmed adherence, antibiotic susceptibility testing should guide further therapy 5, 4, 1, 2