Which is more accurate for diagnosing Helicobacter pylori (H. pylori) in a patient who has recently been on antibiotics and Proton Pump Inhibitors (PPIs), stool antigen (Ag) or serum antibodies (ABs)?

Stool Antigen Test is More Accurate in Patients Recently on Antibiotics and PPIs

In patients who have recently used antibiotics or PPIs, validated IgG serology is the preferred test, but if you must choose between stool antigen and serum antibodies for detecting active infection, the stool antigen test remains superior despite some reduction in accuracy from these medications. 1

Why Serology Should Be Avoided for Active Infection

Serum antibodies (serology) cannot distinguish between current active infection and past exposure, as antibody levels persist for months to years after H. pylori has been eradicated. 1 This fundamental limitation makes serology unsuitable when you need to know if the patient has active infection right now. 1

• Serology tests should never be used to confirm active infection after recent antibiotic exposure because they only indicate exposure at some point in time, not current bacterial presence. 1
• The overall accuracy of commercial ELISA serology tests averages only 78% (range 68-82%), which is inadequate for clinical decision-making. 2
• Serology has approximately 90% sensitivity and specificity at best, but this drops dramatically in populations where many patients have been previously treated. 1

Why Stool Antigen Test Performs Better

The stool antigen test detects active infection by identifying bacterial antigens currently present in stool, with sensitivity and specificity of approximately 93% under optimal conditions. 1, 2

However, recent medication use does affect accuracy:

• PPIs reduce bacterial load in the stomach, causing false-negative results in stool antigen testing. 1
• Antibiotics similarly decrease bacterial density, potentially leading to false-negative results. 1
• Despite these limitations, the stool antigen test still detects active infection when present, unlike serology which cannot make this distinction at all. 2

The Critical Distinction

The key difference: medications cause false-NEGATIVE results in stool antigen testing, but they don't cause false-POSITIVE results. 3 This means:

• If the stool antigen test is positive during or shortly after antibiotics/PPIs, you can trust it—the patient has active infection. 3
• If the stool antigen test is negative during this period, you cannot be certain whether it's truly negative or falsely negative due to medication effects. 3

In contrast, serology remains positive regardless of whether the infection is active or was eradicated months ago, providing no useful information about current infection status. 1

When Serology Has Limited Utility

Serology may be considered only in these specific circumstances:

• When the patient cannot stop PPIs or antibiotics and you need some assessment (though it only tells you about exposure, not active infection). 1
• In patients with gastric atrophy, gastric malignancies, or ulcer bleeding where bacterial load is permanently low and other tests may be falsely negative. 1, 2
• For epidemiologic surveys in populations, not for individual patient diagnosis. 2

Optimal Testing Strategy

The correct approach when recent antibiotics/PPIs are involved:

1. Stop PPIs for at least 2 weeks and antibiotics/bismuth for at least 4 weeks before testing. 1
2. Then perform stool antigen test (laboratory-based monoclonal antibody format) or urea breath test. 1, 2
3. If medications cannot be stopped, validated IgG serology can be used, but understand it only indicates exposure, not active infection. 1
4. Never use rapid in-office stool tests or serology tests—only laboratory-based monoclonal stool antigen tests achieve high accuracy. 1, 2

Common Pitfalls to Avoid

• Do not use serology to diagnose active infection in someone who may have been treated previously—it will remain positive long after eradication. 1
• Do not use rapid in-office stool antigen tests—they have significantly lower accuracy than laboratory-based monoclonal tests. 1
• Do not test during active PPI therapy if avoidable—wait 2 weeks after stopping to avoid 10-40% false-negative rates. 1, 2
• Do not assume a negative stool antigen test is accurate if the patient recently took antibiotics or PPIs—consider retesting after appropriate washout periods. 3