What is the recommended treatment regimen for a patient with a confirmed diagnosis of H. Pylori infection?

Treatment for H. Pylori Infection

Bismuth quadruple therapy for 14 days is the preferred first-line treatment for H. pylori infection in most patients, consisting of a proton pump inhibitor (PPI) twice daily, bismuth (~300mg four times daily), metronidazole (500mg three times daily), and tetracycline (500mg four times daily). 1, 2, 3

First-Line Treatment Regimen

The American College of Gastroenterology recommends bismuth quadruple therapy (BQT) as the preferred first-line regimen because it avoids clarithromycin entirely and maintains high eradication rates despite rising antibiotic resistance patterns. 1, 2, 4

Standard Bismuth Quadruple Therapy Components:

• PPI twice daily (pantoprazole 40mg, lansoprazole 30mg, omeprazole 20mg, esomeprazole 20mg, or rabeprazole 20mg) 2
• Bismuth subsalicylate ~300mg four times daily 1
• Metronidazole 500mg three times daily 1
• Tetracycline 500mg four times daily 1
• Duration: 14 days 1, 2, 3

Alternative First-Line Option (Low Clarithromycin Resistance Areas Only):

• PPI-clarithromycin-amoxicillin triple therapy for 14 days can be used only in areas with documented clarithromycin resistance <15% 2, 3
• This consists of: PPI twice daily, clarithromycin 500mg twice daily, and amoxicillin 1g twice daily 5

Critical Treatment Principles

Treatment duration of 14 days is superior to 7 days and should be standard for all regimens, significantly improving eradication rates regardless of which regimen is chosen. 1, 2, 3

High-dose PPI (twice daily) increases eradication success by approximately 5% compared to standard once-daily dosing and should be used in all regimens. 1, 2, 3

Patient adherence is crucial—incomplete treatment leads to antibiotic resistance and treatment failure. 1, 3 Ensure patients understand the importance of completing the full 14-day course, as this is the most common preventable cause of treatment failure. 6

Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance. 5

Second-Line Treatment After First-Line Failure

After failure of initial therapy, optimized bismuth quadruple therapy for 14 days is the preferred second-line regimen if BQT was not used previously. 1, 2, 4

Levofloxacin-containing triple therapy for 14 days is an alternative second-line option, consisting of levofloxacin 500mg once daily, amoxicillin 1g twice daily, and PPI twice daily for 14 days. 6, 1, 2 However, rising levofloxacin resistance rates must be considered when selecting this regimen. 2, 3

When re-treating after first-line failure, avoid antibiotics used previously to which the bacterium may be resistant. 6 Alternatively, culture and sensitivity testing should be used to ensure appropriate antimicrobial selection. 6

Confirmation of Eradication (Test-of-Cure)

All patients should undergo test-of-cure at least 4 weeks after completing treatment to ensure successful eradication and prevent complications. 1, 2, 3

Preferred Non-Invasive Testing Methods:

• Urea breath test (UBT): 88-95% sensitivity and 95-100% specificity 6, 1
• Laboratory-based validated monoclonal stool antigen test: >90% sensitivity and specificity 1

PPIs must be discontinued at least 2 weeks before testing to avoid false-negative results due to bacterial suppression. 2, 3 Antibiotics and bismuth should also be discontinued within specified washout periods. 1, 3

When Endoscopy-Based Testing is Mandatory:

Endoscopy with biopsy is required for confirmation of eradication in:

• Complicated peptic ulcer disease 6
• Gastric ulcer (to exclude malignancy, as some gastric malignancies can only be detected during or following the healing process) 6
• Low-grade gastric MALT lymphoma (to evaluate regression of malignancy) 6, 1

When performing endoscopy-based testing, obtain two biopsy specimens from both the antrum and body, plus one for rapid urease test. 6

Special Clinical Contexts

Bleeding Peptic Ulcer:

In patients with bleeding peptic ulcer and confirmed H. pylori infection, eradication therapy is strongly recommended to prevent recurrent bleeding. 6, 1 Start standard triple therapy after 72-96 hours of intravenous PPI administration and administer for 14 days. 6

All patients with bleeding peptic ulcer should undergo H. pylori testing, as eradication reduces rebleeding rates from 26% to minimal levels. 6 Empirical antimicrobial therapy without confirmed H. pylori infection is not recommended. 6

Peptic Ulcer Disease:

Eradication of H. pylori in patients with peptic ulcer disease reduces ulcer recurrence risk by >90%. 1 Non-recurrence of gastric and duodenal ulcer is strictly dependent on successful H. pylori eradication. 6

Gastric MALT Lymphoma:

Eradication is recommended as primary therapy for low-grade gastric MALT lymphoma, with confirmation of successful eradication mandatory in these patients. 6, 1

Special Populations

Penicillin Allergy:

• In high clarithromycin resistance areas: Use bismuth-containing quadruple therapy 2, 3
• In low clarithromycin resistance areas: Use PPI-clarithromycin-metronidazole combination for 14 days 2, 3

Renal Impairment:

Patients with severe renal impairment (GFR <30 mL/min) require dose adjustments:

• GFR 10-30 mL/min: Amoxicillin 500mg or 250mg every 12 hours 5
• GFR <10 mL/min: Amoxicillin 500mg or 250mg every 24 hours 5
• Hemodialysis: Administer additional dose both during and at the end of dialysis 5

Pediatric Patients:

H. pylori treatment in children should be conducted by pediatric specialists in specialized centers, not in primary care. 3 Weight-based dosing is mandatory and differs substantially from adult regimens. 3

Tetracycline should not be used in children under 8 years due to risk of permanent tooth discoloration and impaired bone growth. 3 Fluoroquinolones should be avoided in children due to risk of cartilage damage and tendon rupture. 3

Key Clinical Pitfalls to Avoid

Never perform H. pylori testing while a patient is taking PPIs, antibiotics, or bismuth within the specified washout periods, as bacterial suppression will yield false-negative results. 1, 2, 3 PPIs must be stopped at least 2 weeks before testing. 2

Antibiotic resistance is the most important factor responsible for eradication failure—local surveillance of resistance patterns is mandatory for optimal treatment selection. 1, 2, 3, 4

Avoid monotherapy or inappropriate regimens to minimize development of antibiotic resistance. 6, 3 The risk of antibiotic resistance must be minimized by avoiding use of inappropriate regimens and ensuring high patient compliance. 6

In uncomplicated peptic ulcer disease where symptoms resolve, test-of-cure may not be necessary, as symptom assessment at 3 and 6 months has been shown to be as valuable as the urea breath test in determining ulcer cure following eradication therapy. 6 However, this is the exception—most patients should undergo formal test-of-cure. 1, 2, 3