What is the recommended approach to test for Helicobacter pylori infection, including non‑invasive and endoscopic methods and required medication washout?

How to Test for Helicobacter pylori

Use the ¹³C-urea breath test or laboratory-based monoclonal stool antigen test as your first-line diagnostic method in patients under 50 years without alarm symptoms, after stopping proton pump inhibitors for at least 2 weeks and antibiotics/bismuth for at least 4 weeks. 1, 2

Medication Washout Requirements (Critical First Step)

Before ordering any H. pylori test except serology, ensure proper medication washout to avoid false-negative results:

• Stop PPIs for ≥2 weeks before urea breath test, stool antigen test, rapid urease test, histology, or culture 1, 2
• Stop antibiotics and bismuth for ≥4 weeks before any testing 1
• PPIs cause 10-40% false-negative rates by suppressing bacterial load, making this washout period non-negotiable 1
• Serology is the only test unaffected by ongoing PPI therapy and can be performed without washout, though it has significant limitations 1

Algorithm for Test Selection

For Patients <50 Years Without Alarm Symptoms

Use non-invasive testing with a "test-and-treat" strategy:

• First choice: ¹³C-urea breath test (sensitivity 94-97%, specificity 95-97.7%) 1, 2
• Equally acceptable alternative: Laboratory-based monoclonal stool antigen test (sensitivity and specificity ~93%) 1, 2, 3
• This approach reduces unnecessary endoscopies by 62% while maintaining equivalent safety 1
• Never use rapid in-office immunochromatographic stool tests (accuracy only 80-81%) 2

For Patients ≥50-55 Years or Any Age With Alarm Symptoms

Proceed directly to endoscopy with invasive testing:

• Alarm symptoms mandating immediate endoscopy include: 1

  • Unintentional weight loss
  • Dysphagia (difficulty swallowing)
  • Gastrointestinal bleeding or anemia
  • Palpable abdominal mass
  • Recurrent vomiting
  • Family history of gastric cancer

• During endoscopy, obtain biopsies from both antrum and body (single biopsies miss 10% of infections due to patchy colonization) 1

• Invasive test options during endoscopy: 1, 2

  • Rapid urease test (sensitivity 80-95%, specificity 95-100%)
  • Histology with modified Giemsa staining (sensitivity 90-95%, specificity 95-98%)
  • Culture with antimicrobial susceptibility testing (particularly valuable after treatment failure or in regions with >15-20% clarithromycin resistance)

When to Use Serology (Limited Indications Only)

Serology should NOT be used for routine diagnosis because it cannot distinguish active infection from past exposure and has poor accuracy (overall 78%, range 68-82%). 1, 2

Consider validated IgG serology only when: 1, 2

• Patient cannot stop PPIs/antibiotics and testing cannot be delayed
• Gastric atrophy, malignancy, or ulcer bleeding present (where bacterial load is low and other tests may be falsely negative)
• Large epidemiologic surveys in high-prevalence populations

Post-Treatment Confirmation of Eradication

Test ≥4 weeks after completing eradication therapy using: 1, 2, 3

• ¹³C-urea breath test (preferred)
• Laboratory-based monoclonal stool antigen test (equally acceptable)
• Never use serology to confirm eradication (antibodies persist for months to years) 2

Ensure medication washout before confirmation testing: 1

• PPIs stopped ≥2 weeks
• Antibiotics/bismuth stopped ≥4 weeks

Critical Pitfalls to Avoid

• Do NOT test patients currently taking PPIs unless serology is deliberately chosen or proper washout completed 1
• Do NOT use rapid in-office stool antigen kits—always specify laboratory-based monoclonal assay 1, 2
• Do NOT use serology panels (IgG/IgA/IgM)—they add no value beyond validated IgG testing 1
• Do NOT obtain single antral biopsies during endoscopy—always sample both antrum and body 1
• Do NOT use serology for post-treatment confirmation—it remains positive after eradication 2
• Do NOT test patients with typical irritable bowel syndrome rather than dyspepsia 1

Special Populations

• Children and pregnant women: Use ¹³C-urea breath test (safe) or stool antigen test; avoid ¹⁴C-urea breath test (radioactive) 1
• Regions with high clarithromycin resistance (>15-20%): Obtain culture with susceptibility testing before first-line treatment 1, 2
• Patients with family history of gastric cancer: Require urgent endoscopy regardless of age 1