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

Treatment of Helicobacter pylori Ulcers

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

First-Line Treatment Regimen

Bismuth quadruple therapy achieves eradication rates of 80-90% and is preferred because:

• Clarithromycin resistance now exceeds 15% in most regions of North America, making traditional triple therapy unacceptably ineffective 1
• Bacterial resistance to bismuth is extremely rare, making this regimen effective even against metronidazole-resistant strains 1, 2
• The World Health Organization has identified H. pylori as requiring urgent investment in new antibiotics due to high clarithromycin resistance rates 1
• This regimen 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

Treatment duration of 14 days is mandatory - extending from 7 to 14 days improves eradication success by approximately 5% 1, 2

High-dose PPI (twice daily) is essential - this increases eradication efficacy by 6-10% compared to standard doses by reducing gastric acidity and enhancing antibiotic activity 2

Alternative First-Line Options (When Bismuth Unavailable)

Concomitant non-bismuth quadruple therapy for 14 days:

• PPI twice daily + amoxicillin 1000 mg twice daily + metronidazole 500 mg twice daily + clarithromycin 500 mg twice daily 1, 2
• This is the preferred alternative when bismuth quadruple therapy cannot be used 1
• Critical caveat: Avoid this regimen if the patient has had previous clarithromycin exposure due to potential resistance 1, 2

Triple therapy (only in areas with clarithromycin resistance <15%):

• PPI twice daily + clarithromycin 500 mg twice daily + amoxicillin 1000 mg twice daily for 14 days 1, 2
• This option should be abandoned in regions where clarithromycin resistance exceeds 15-20% 1, 2

Second-Line Treatment After First-Line Failure

After failure of clarithromycin-containing therapy:

• Bismuth quadruple therapy (if not previously used) 2
• 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 2
• Important: Levofloxacin should not be used empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates 1

Third-Line and Rescue Therapies

After two failed eradication attempts:

• Antimicrobial susceptibility testing should guide further treatment 1, 2
• Rifabutin-based triple therapy (PPI + amoxicillin + rifabutin 150 mg twice daily) for 14 days is an acceptable rescue option 1, 2
• High-dose dual amoxicillin-PPI therapy is an alternative rescue therapy 1

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
• Do not use serology - antibodies may persist long after successful treatment 2

Managing Side Effects

Diarrhea occurs in 21-41% of patients during the first week:

• Consider adjunctive probiotics to reduce the risk of diarrhea and improve patient compliance 1
• Probiotics help reduce antibiotic-associated diarrhea, though evidence for increased eradication rates is limited 2

Critical Pitfalls to Avoid

• Never repeat antibiotics to which the patient has been previously exposed, especially clarithromycin and levofloxacin 1, 2
• Never use inadequate PPI dosing - always use high-dose (twice daily) PPI as this significantly reduces treatment efficacy 2
• Never use triple therapy in areas with clarithromycin resistance >15% - this results in unacceptably low eradication rates 1, 2
• For penicillin allergy: Amoxicillin can be replaced with tetracycline 2; consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 1
• In children: Fluoroquinolones and tetracyclines should not be used, limiting treatment options 2

Dosing Considerations for Amoxicillin Component

For adults with H. pylori infection:

• Amoxicillin should be taken at the start of a meal to minimize gastrointestinal intolerance 3
• Standard dosing is 1000 mg twice daily as part of triple therapy regimens 3