H. pylori Infection: Clinical Presentation and Treatment
Clinical Manifestations
Most H. pylori infections are asymptomatic, but when symptoms occur, they typically manifest as chronic dyspepsia, epigastric pain, or complications including peptic ulcer disease and gastric cancer. 1, 2
Symptomatic Presentations
- Dyspepsia: Chronic upper abdominal discomfort, bloating, or pain that may worsen with eating 2
- Peptic ulcer disease: Epigastric pain that may be relieved by food or antacids, with approximately 17% lifetime risk among infected individuals 1
- Gastric cancer risk: Lifetime risk varies from 0.6% to 22% depending on geographic region, with H. pylori being the primary etiologic factor 1
- MALT lymphoma: Low-grade gastric mucosa-associated lymphoid tissue lymphoma directly caused by chronic H. pylori infection 1, 2
Asymptomatic Infection
- The majority of infected individuals remain asymptomatic throughout their lives, yet still carry increased risk for peptic ulcer and gastric cancer 1, 2
- Family clustering is common due to childhood transmission within households, increasing risk for relatives 1
Diagnostic Testing Approach
When Symptoms Are Present (Endoscopy Indicated)
Use biopsy-based detection methods during endoscopy: rapid urease test, histology, or culture—performing more than one test increases diagnostic sensitivity. 3
- Obtain at least 2 biopsies from both antrum and body, plus 1 for rapid urease test 1
- Histological assessment is mandatory for gastric ulcers to exclude malignancy 1
When Symptoms Are Absent or Mild (Non-Invasive Testing)
The urea breath test is the gold standard non-invasive test for detecting active H. pylori infection. 3, 4, 5
- Alternative: Monoclonal stool antigen test if breath test unavailable 1, 6
- Avoid serology for confirming active infection—it only indicates prior exposure, not current infection 3, 4
Critical Testing Pitfalls
- Stop PPIs 2 weeks before testing to avoid false-negative results 6, 7
- Wait at least 4 weeks after treatment completion before testing for eradication 1, 3
- Never use serology to confirm eradication—antibodies persist long after successful treatment 6, 3
First-Line Treatment: Bismuth Quadruple Therapy
Bismuth quadruple therapy for 14 days is the preferred first-line treatment, achieving 80-90% eradication rates even in areas with high clarithromycin and metronidazole resistance. 1, 6, 7
Standard Regimen Components
- PPI: High-dose twice daily (e.g., esomeprazole or rabeprazole 40 mg BID) taken 30 minutes before meals 6, 8
- Bismuth subsalicylate: 262 mg four times daily OR bismuth subcitrate 120-140 mg 3-4 times daily 6, 8
- Metronidazole: 500 mg three to four times daily (total 1.5-2 g/day) 6, 8
- Tetracycline HCl: 500 mg four times daily 6, 8
Why Bismuth Quadruple Therapy Works
- No bacterial resistance to bismuth has ever been described, making it uniquely effective 1, 6, 8
- Bismuth's synergistic effect overcomes metronidazole resistance even when present in vitro 1, 8
- Tetracycline resistance remains rare (<5% in most regions) 6, 8
- Uses antibiotics from WHO "Access group" rather than "Watch group," supporting antimicrobial stewardship 6
Critical Optimization Factors
- 14-day duration is mandatory—improves eradication by approximately 5% compared to 7-10 day regimens 1, 6, 7
- High-dose PPI twice daily increases cure rates by 6-10% compared to standard dosing 6
- Using potent PPIs (esomeprazole or rabeprazole 40 mg BID) may increase cure rates by an additional 8-12% 6
Alternative First-Line Option: Rifabutin Triple Therapy
For patients without penicillin allergy, rifabutin triple therapy for 14 days is an acceptable alternative with rare bacterial resistance. 6, 9, 7
Regimen
- Rifabutin: 150 mg twice daily 6, 9
- Amoxicillin: 1000 mg twice daily 6, 9
- PPI: High-dose twice daily 6, 9
When Bismuth Is Unavailable: Concomitant Therapy
Concomitant non-bismuth quadruple therapy for 14 days is the recommended alternative when bismuth is not available. 6, 7
Regimen
- PPI: Twice daily 6
- Amoxicillin: 1000 mg twice daily 6
- Clarithromycin: 500 mg twice daily 6
- Metronidazole: 500 mg twice daily 6
Important Caveat
This regimen should only be used in areas where clarithromycin resistance is <15%, which excludes most of North America and much of Europe. 1, 6
Regimens to AVOID as First-Line Therapy
Do NOT use standard clarithromycin triple therapy empirically—clarithromycin resistance now exceeds 15% in most regions, reducing eradication rates to approximately 20% with resistant strains versus 90% with susceptible strains. 1, 6
Do NOT use levofloxacin empirically as first-line therapy due to rapidly rising fluoroquinolone resistance rates (11-30% primary resistance). 6
Avoid concomitant, sequential, or hybrid therapies that include unnecessary antibiotics contributing to global antibiotic resistance. 1, 6
Second-Line Treatment After First Failure
If Bismuth Quadruple Therapy Was NOT Used First-Line
Use optimized bismuth quadruple therapy for 14 days as described above. 6, 9, 7
If Bismuth Quadruple Therapy Failed
Levofloxacin triple therapy for 14 days is the preferred second-line option if the patient has no prior fluoroquinolone exposure. 6, 7
Regimen
- PPI: Twice daily 6
- Amoxicillin: 1000 mg twice daily 6
- Levofloxacin: 500 mg once daily OR 250 mg twice daily 6
Critical Principle
Never repeat antibiotics previously used, especially clarithromycin and levofloxacin, where resistance develops rapidly after exposure. 6, 9
Third-Line and Rescue Therapies
After two failed eradication attempts with confirmed patient adherence, antibiotic susceptibility testing should guide further treatment whenever possible. 1, 6, 9, 7
When Susceptibility Testing Is Unavailable
Rifabutin triple therapy for 14 days is the preferred rescue option. 6, 9, 7
Alternative: High-dose dual amoxicillin-PPI therapy for 14 days 6
- Amoxicillin 2-3 grams daily in 3-4 split doses + high-dose PPI twice daily 6
Confirmation of Eradication
Test for eradication success at least 4 weeks after treatment completion using urea breath test or monoclonal stool antigen test. 1, 6, 9, 7
Testing Protocol
- Discontinue PPI at least 2 weeks before testing to avoid false-negative results 6, 7
- Never use serology to confirm eradication—antibodies persist indefinitely after successful treatment 6, 3
When Confirmation Is Mandatory
- Complicated peptic ulcer disease 1
- Gastric ulcer (also requires endoscopy to exclude malignancy) 1
- Gastric MALT lymphoma 1
- Poor patient compliance during treatment 1
Special Populations
Patients with Penicillin Allergy
Bismuth quadruple therapy is the first choice, as it contains tetracycline, not amoxicillin. 6, 8
- Consider penicillin allergy testing to enable amoxicillin use, as amoxicillin resistance remains rare 6
Pediatric Patients
Treatment should only be conducted by pediatric specialists in specialized centers. 6
- Neither fluoroquinolones nor tetracyclines can be used in children, considerably limiting options 8
Patient Factors Affecting Treatment Success
Modifiable Risk Factors
- Smoking: Increases eradication failure risk (OR 1.95) 6
- Poor compliance: Accounts for >10% of treatment failures 6
- Inadequate PPI dosing: Significantly reduces efficacy—always use high-dose twice daily 6, 9
Non-Modifiable Risk Factors
- High BMI: Obesity increases failure risk due to lower drug concentrations at gastric mucosal level 6
Common Pitfalls and How to Avoid Them
PPI Administration Errors
PPIs must be taken 30 minutes before meals on an empty stomach, without concomitant antacids, to maximize absorption and activation. 6, 9
- Standard once-daily PPI dosing is inadequate—always use twice-daily 6
- Pantoprazole should be avoided due to relatively lower potency 8
Antibiotic Selection Errors
Do not assume low clarithromycin resistance without local surveillance data—most regions now have high resistance rates. 6
Avoid using doxycycline as a substitute for tetracycline—multiple studies show significantly inferior results. 8
Treatment Duration Errors
7-10 day regimens are inadequate—always use 14 days to maximize first-attempt success. 1, 6, 7
Adjunctive Therapies
Probiotics
Probiotics can reduce antibiotic-associated diarrhea (which occurs in 21-41% of patients) and improve compliance, but do not significantly increase eradication rates. 6, 2