Do you need to stop taking Proton Pump Inhibitors (PPIs) before testing for Helicobacter pylori (H pylori)?

Should You Stop PPIs Before H. pylori Testing?

Yes, PPIs should be stopped for 2 weeks before H. pylori testing when using culture, histology, rapid urease test, urea breath test, or stool antigen test. 1

The Core Recommendation

The Maastricht IV/Florence Consensus Report provides clear guidance with high-quality evidence (Evidence level 1b, Grade A recommendation): if possible, discontinue PPIs for 2 weeks before performing any H. pylori diagnostic test except serology. 1

Why PPIs Interfere with Testing

PPIs fundamentally alter the gastric environment in ways that compromise test accuracy:

• PPIs increase gastric pH, causing the H. pylori bacterial load to decrease dramatically, especially in the antrum, leading to false-negative results in 10-40% of cases. 1
• This effect impacts nearly all diagnostic modalities: urea breath tests, stool antigen tests, rapid urease tests, culture, and histology. 1
• The bacteria don't disappear—they just become undetectable due to reduced bacterial density. 1

The 2-Week Washout Period

Stopping PPIs for 2 weeks allows H. pylori to repopulate the stomach, restoring test sensitivity. 1, 2

However, important caveats exist:

• Research suggests that 12 days may be the minimum required for complete bacterial recovery and restoration of urease activity. 3
• No studies have adequately evaluated the necessary washout period after long-term PPI use, so the 2-week recommendation may be conservative but prudent. 1
• Different PPIs may have varying effects—omeprazole and lansoprazole appear to cause more false-negatives than pantoprazole—but the 2-week washout applies to all PPIs. 2, 3

When You Cannot Stop PPIs

If stopping PPIs is not clinically feasible, use validated IgG serology instead (Evidence level 2b, Grade B recommendation). 1

Serology remains accurate during PPI use because:

• IgG antibodies against H. pylori persist for months or even years regardless of transient decreases in bacterial load. 1
• Serology is the only test unaffected by PPI-induced changes in the stomach. 1, 4
• Only validated commercial ELISA tests with >90% accuracy should be used—avoid rapid in-office serological tests. 1, 4

What About H2 Receptor Antagonists?

H2 blockers like famotidine can also cause false-negatives, but to a much lesser extent than PPIs. 1, 4

• The consensus panel did not find it necessary to routinely stop H2 blockers before testing. 1
• However, if stopping famotidine is feasible, a 2-week washout is still recommended for optimal accuracy. 4

Common Clinical Pitfalls to Avoid

• Failing to ask about over-the-counter PPI use—many patients self-medicate for dyspepsia without reporting it. 1, 2
• Sampling only one gastric region (antrum or body) increases the likelihood of missing active infection by at least 15%, especially in PPI users where bacterial distribution becomes patchy. 5
• Using non-validated serological tests when PPIs cannot be stopped—accuracy varies wildly among commercial kits. 1, 2
• Assuming all stool antigen tests are equally affected—newer bioluminescent enzyme immunoassay tests (like BLEIA®) maintain extremely high sensitivity (95.8-100%) even during PPI use, though the 2-week washout remains the gold standard. 6

Special Testing Scenarios

In bleeding peptic ulcer disease, where stopping PPIs is not an option, urea breath testing after initial biopsy-based tests is recommended to rule out false-negative results. 7

When endoscopy is performed for other reasons in PPI users, consider taking biopsies from both antrum and body, as bacterial distribution becomes irregular during acid suppression. 5