Should Proton Pump Inhibitors (PPIs) be stopped before a stool H. pylori (Helicobacter pylori) antigen test?

Should PPIs Be Stopped Before Stool H. pylori Antigen Testing?

Yes, PPIs should be stopped for at least 2 weeks before performing a stool H. pylori antigen test to avoid false-negative results. 1

Why PPIs Must Be Discontinued

• PPIs increase gastric pH, which decreases H. pylori bacterial load in the stomach, particularly in the antrum, leading to false-negative results in 10-40% of cases 1
• This effect applies to all tests detecting active infection, including stool antigen tests, urea breath tests, rapid urease tests, culture, and histology 1
• The stool antigen test has excellent accuracy (>90% sensitivity and specificity) in untreated patients, but this performance deteriorates significantly when PPIs are not discontinued 1

Recommended Washout Periods

For stool antigen testing specifically:

• PPIs should be withheld for at least 2 weeks before testing 1
• Some evidence suggests at least 7 days may be sufficient, though 2 weeks is the standard recommendation 1
• Antibiotics and bismuth products should be withheld for at least 4 weeks 1
• One in vitro study suggests complete bacterial recovery may require up to 12 days after PPI cessation 2

Important caveat: The optimal washout period after long-term PPI therapy has not been well-studied, and longer periods may be needed in these patients 1

What If PPIs Cannot Be Stopped?

• If stopping PPIs is not possible due to symptom management needs, validated IgG serology can be performed instead as it is the only test unaffected by PPI use 1, 3
• Serology detects antibodies rather than active infection and remains positive despite transient decreases in bacterial load 1
• However, serology should only be used for initial diagnosis, not for confirming eradication, as antibodies remain elevated for months to years after treatment 1

Critical Clinical Point About Positive Results

• A positive stool antigen test result can be trusted even if the patient is on PPIs, as PPIs cause false-negative results but not false-positive results 1, 4
• If a test is positive despite PPI use, proceed with treatment—do not repeat testing 4
• Only negative results during PPI therapy should prompt concern about accuracy 1

Common Pitfalls to Avoid

• Failing to inquire about over-the-counter PPI use, which is increasingly common and may not be reported by patients 3
• Using office-based rapid serologic tests instead of laboratory-based ELISA tests, which have significantly lower accuracy 1
• Inadequate washout period, particularly after long-term PPI treatment 1, 3
• Substituting H2-receptor antagonists is acceptable, as they do not significantly affect bacterial load 1

Alternative Testing Strategy

• Histamine-2 receptor antagonists can be substituted for PPIs during the washout period without affecting test accuracy 1
• If there is doubt about a false-negative result, repeat testing after at least 2 weeks off all interfering medications 1