The bacterium Clostridioides difficile, often shortened to C. diff, is a major cause of diarrhea and inflammation of the colon. This organism proliferates when the normal gut flora is disrupted, commonly following antibiotic use. Since its symptoms resemble other infectious diarrheas, an accurate laboratory diagnosis is necessary to confirm a C. diff infection (CDI) and guide treatment. The C. diff antigen test, known as the Glutamate Dehydrogenase (GDH) test, is frequently the first step in a diagnostic strategy used to detect the presence of the organism in a patient’s stool sample.
The C. diff Antigen and Its Purpose
The specific antigen targeted by this test is an enzyme called Glutamate Dehydrogenase (GDH). This enzyme is produced in large quantities by all strains of the C. diff bacterium, regardless of whether they are capable of producing toxins that cause disease. Because GDH is an abundant structural protein, its detection serves as a marker for the presence of the C. diff organism in the stool.
The GDH test is a type of immunoassay, which uses antibodies engineered to specifically bind to the GDH enzyme found in the sample. If the target antigen is present, the test yields a positive result, indicating the bacterium is colonizing the patient’s gut. The test is known for its high sensitivity, meaning it is effective at correctly identifying samples that contain the C. diff organism. A negative GDH result is reliable for ruling out the presence of the bacteria and, consequently, a C. diff infection.
How Antigen Testing Fits Into Diagnosis
While the GDH antigen test is sensitive, it lacks the specificity needed to diagnose an active infection because it cannot distinguish between a toxigenic (disease-causing) strain and a non-toxigenic strain. A positive GDH result only confirms colonization, which can occur in asymptomatic individuals. True C. diff infection, or CDI, is caused by the toxins (Toxin A and Toxin B) that some strains produce.
For this reason, the GDH antigen test is rarely used as a standalone diagnostic tool; instead, it functions as an initial screening step within a multi-step laboratory testing protocol. This algorithmic approach, often called a two-step algorithm, is designed to be cost-effective and accurate. When a stool sample tests positive for the GDH antigen, the laboratory will automatically perform a second, more specific test to check for the presence of the toxins or the toxin genes.
The second test is often an enzyme immunoassay (EIA) to detect Toxin A/B or a Nucleic Acid Amplification Test (NAAT), such as PCR, which detects the genes responsible for toxin production. The GDH test acts as a gatekeeper; if the GDH screen is negative, no further testing is required, quickly clearing the patient of a C. diff diagnosis. If the GDH test is positive, the subsequent testing determines if the colonization is a true, active infection requiring treatment.
Understanding the Test Results
The final diagnosis of a C. diff infection relies on the combined results of the GDH antigen test and the subsequent toxin or NAAT test. There are four main result combinations that clinicians use for interpretation.
GDH Negative Result
The most straightforward result is a GDH negative result, which effectively excludes C. diff as the cause of diarrhea, and no further testing is needed.
GDH Positive and Toxin/NAAT Positive
A positive GDH result followed by a positive Toxin A/B or NAAT result indicates an active C. diff infection. The presence of the organism is confirmed alongside the presence of the disease-causing toxins or toxin genes, which typically requires immediate clinical treatment. This result confirms that a toxigenic strain is present and potentially responsible for the patient’s symptoms.
GDH Positive and Toxin/NAAT Negative (Discordant Result)
The most complex result is a GDH positive result with a negative Toxin A/B or NAAT result, often called a discordant result. This finding means the C. diff organism is present in the gut, but the toxins or toxin genes were not detected. This outcome often signifies colonization with a non-toxin-producing strain or a toxigenic strain that is not actively producing detectable levels of toxin. In such cases, the patient may not have an active CDI, and treatment decisions are made based on the severity of the patient’s clinical symptoms and other medical factors.