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

Treatment Recommendations for Adults with H. pylori Infection

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

First-Line Treatment Regimen

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, 3

The specific regimen consists of:

• PPI (standard dose) twice daily - taken 30 minutes before meals on an empty stomach 1
• 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, 2
• Tetracycline 500 mg four times daily 1, 2
• Duration: 14 days 1, 2, 3

Critical Optimization Factors

Use high-potency PPIs at high doses—esomeprazole or rabeprazole 40 mg twice daily increases cure rates by 8-12% compared to other PPIs. 1, 4 Standard once-daily PPI dosing is inadequate and significantly reduces treatment efficacy. 1, 4

The 14-day duration is mandatory, as it improves eradication by approximately 5% compared to 7-10 day regimens. 1, 2, 3

Why Bismuth Quadruple Therapy is Preferred

• No bacterial resistance to bismuth has been described 1
• Tetracycline and amoxicillin resistance remains rare (<5%) 1
• Bismuth's synergistic effect overcomes metronidazole resistance in vitro 1
• Uses antibiotics from the WHO "Access group" rather than "Watch group," making it preferable from an antimicrobial stewardship perspective 1
• Clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective 1, 4

Alternative First-Line Options (When Bismuth is Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth is not available. 1, 2

This consists of:

• PPI twice daily 1
• Amoxicillin 1000 mg twice daily 1, 5
• Clarithromycin 500 mg twice daily 1
• Metronidazole 500 mg twice daily 1
• Duration: 14 days 1

This regimen avoids the pitfall of sequential therapy by administering all antibiotics simultaneously, preventing the development of resistance during treatment. 1

Second-Line Treatment After First-Line Failure

After bismuth quadruple therapy failure, levofloxacin-based triple therapy for 14 days is recommended if the patient has no prior fluoroquinolone exposure. 1, 2, 3

The regimen consists of:

• PPI twice daily 1
• Amoxicillin 1000 mg twice daily 1, 5
• Levofloxacin 500 mg once daily or 250 mg twice daily 1, 2
• Duration: 14 days 1

Critical caveat: Rising rates of levofloxacin resistance (11-30% primary, 19-30% secondary) make this unsuitable as empiric first-line therapy. 1 The FDA recommends fluoroquinolones be used as a last choice due to risk of serious side effects. 1

Never reuse 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 with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment whenever possible. 1, 2, 3

Rifabutin Triple Therapy

Rifabutin-based triple therapy for 14 days is a reasonable rescue option after multiple failures. 1, 2, 3

The regimen consists of:

• Rifabutin 150 mg twice daily 1
• Amoxicillin 1000 mg twice daily or three times daily 1, 5
• High-dose PPI twice daily 1
• Duration: 14 days 1

Rifabutin resistance is rare, making it highly effective as rescue therapy. 1 However, rifabutin should be reserved for patients who have failed previous eradication attempts with other antibiotics. 1

High-Dose Dual Amoxicillin-PPI Therapy

High-dose dual amoxicillin-PPI therapy for 14 days is an alternative rescue therapy when other options have been exhausted. 1

The regimen consists of:

• Amoxicillin 2-3 grams daily in 3-4 split doses 1
• High-dose PPI (double standard dose) twice daily 1
• Duration: 14 days 1

Special Populations

Patients with Penicillin Allergy

Bismuth quadruple therapy is the first choice in patients with penicillin allergy, as it contains tetracycline, not amoxicillin. 1, 2

Consider penicillin allergy testing to delist the allergy and enable amoxicillin use, as many reported penicillin allergies are not true IgE-mediated reactions. 1 Amoxicillin resistance remains extremely rare (<5%), making it a highly reliable antibiotic when it can be used. 1

Patients with Obesity

High BMI increases risk of treatment failure due to lower drug concentrations at the gastric mucosal level. 1 Consider this when counseling patients about expected success rates.

Smokers

Smoking is a risk factor for eradication failure, with an odds ratio of 1.95 for failure among smokers versus non-smokers. 1 Counsel patients to stop smoking during treatment.

Verification of Eradication

Confirm eradication with urea breath test or validated monoclonal stool antigen test at least 4 weeks after completion of therapy and at least 2 weeks after PPI discontinuation. 1, 2, 4

Never use serology to confirm eradication—antibodies may persist long after successful treatment, yielding false-positive results. 1

Sucralfate must be discontinued at least 4 weeks before H. pylori testing to avoid false-negative results, as it can suppress but not eradicate the bacteria. 2

Common Pitfalls and How to Avoid Them

Inadequate PPI Dosing

Standard once-daily PPI dosing is inadequate—always use high-dose (twice daily) PPI, preferably esomeprazole or rabeprazole 40 mg. 1, 4 This single factor can reduce treatment efficacy by 6-12%. 1

Using Clarithromycin Empirically

Never assume low clarithromycin resistance without local surveillance data—most regions now have resistance rates exceeding 20%. 1, 4 When H. pylori strains are clarithromycin-resistant, eradication rates drop from 90% to approximately 20%. 1

Avoid repeating clarithromycin if the patient has prior macrolide exposure for any indication, as cross-resistance is universal within the macrolide family. 1

Insufficient Treatment Duration

Seven-day regimens are obsolete—always use 14-day treatment to maximize first-attempt success. 1, 2, 3 The 5% improvement in eradication rates with 14 days versus 7-10 days is clinically significant. 1, 2

Poor Patient Compliance

More than 10% of patients are poor compliers, leading to much lower eradication rates. 1 Address compliance issues proactively:

• Counsel patients about the importance of completing the full 14-day course 1
• Warn about potential side effects, particularly diarrhea (occurs in 21-41% during first week) 1
• Consider adjunctive probiotics to reduce antibiotic-associated diarrhea and improve compliance 1, 4

Repeating Failed Antibiotics

Never reuse antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin. 1, 2 However, metronidazole can be reused with bismuth because bismuth's synergistic effect overcomes in vitro resistance. 1 Amoxicillin and tetracycline can also be reused because resistance to these agents remains rare. 1

Adjunctive Therapies

Probiotics can be used as adjunctive treatment to reduce side effects, particularly antibiotic-associated diarrhea, though evidence for increasing eradication rates is limited. 1, 2, 4 The benefit is primarily in preventing side effects and improving compliance, not in directly enhancing eradication. 1

The Paradigm Shift in H. pylori Management

H. pylori gastritis should be treated as an infectious disease with the goal of near-100% cure rates, not as a typical gastroenterological disease with modest success rates. 1 The primary outcome variable should be actual cure rate, prioritizing morbidity and mortality reduction through gastric cancer prevention. 6