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CDI Testing
Diagnosing CDI: Differentiating Between Stool Assays

Released: March 29, 2023

Paul Feuerstadt
Paul Feuerstadt, MD, FACG, AGAF
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Key Takeaways
  • The 3 main commercially available stool assays to detect CDI are the enzyme-linked immunoassay (EIA), the glutamate dehydrogenase (GDH) assay, and the polymerase chain reaction (PCR) test.
  • Combining the EIA and GDH test is more accurate and effective than using either test alone.
  • Use of the PCR assay alone may result in overdiagnosis; consider the clinical context of the patient to support their diagnosis.

In a world where we want information instantaneously and we can control most of our lives through a mobile phone, it is surprising that we do not have a single test or group of tests that are optimized for the diagnosis of the most common healthcare-associated infection, Clostridioides difficile infection (CDI). 

There are 3 main commercially available stool assays that can be used to detect CDI, including the enzyme linked immunoassay (EIA), the glutamate dehydrogenase (GDH) assay, and the polymerase chain reaction (PCR) test. Each of these tests have merit on their own but none is ideal as a single test for the diagnosis of CDI without further consideration. 

Enzyme-Linked Immunoassay
The EIA is a test that detects the presence or absence of the toxin released by C. difficile. This is the only commercially available test that is able to diagnose active CDI because, for this test to be positive, the bacteria needs to be present and actively releasing the toxins that are presumed to cause the symptoms most commonly associated with CDI, including abdominal pains, fevers and diarrhea.

With that concept in mind, you must be asking yourself, “Why we do not use this test exclusively to diagnose the infection?” The answer is that this test suffers from suboptimal sensitivity. If the test is positive, you can assume that the patient has the active infection; however, if it is negative, you can’t assume they do not have CDI.

Glutamate Dehydrogenase Assay
As a result of low sensitivity of the EIA, the GDH assay is typically paired with the EIA. The GDH assay detects the presence or absence of GDH, which is an enzyme that is broadly released by Clostridioides species, but not specifically by the type of C. difficile that releases toxins and causes symptoms. If this test is negative, it is highly unlikely the patient has CDI, but if it is positive, you can’t assume they do. 

When combining the EIA and GDH tests, you get a more accurate and effective CDI assessment. If both the EIA and GDH tests are positive, the patient most likely has CDI, and if both tests are negative, then the patient is extremely unlikely to have CDI.

Polymerase Chain Reaction 
Sometimes the results of the EIA and GDH tests are discordant. In that circumstance, we use the PCR assay to adjudicate. The PCR test is an assay that evaluates the presence or absence of the genes that code for the toxins of CDI, but not the toxin itself. When there are discordant results from EIA and GDH, if the PCR test is positive, the patient is positive. If the PCR test is negative, the patient is negative. 

Unfortunately, the PCR assay is frequently used as a single test for CDI. In that circumstance, the test has a tendency to overdiagnose CDI. Many individuals have the bacterium C. difficile in their system but the bacteria may not be releasing toxins, in which case, they do not have an active infection and are considered “colonizers.” If the PCR test is performed in these cases, an inappropriate diagnosis may result. 

Given this limitation, when a PCR assay is used as a solitary test, it should be sent only when the patient is having at least 2 consecutive days of 3 or more liquid bowel movements in a 24-hour period with the stools taking the shape of the specimen collection container. If that clinical context is provided, then this test can be a good measure for the presence or absence of the infection.

Best Practices for Testing 
Detection of CDI remains a challenge, but if the actual diagnostic methods are understood, then we can have optimized approaches using either the combination of EIA and GDH tests with adjudication of discordant results through the PCR assay or with providing a clinical context and sending the PCR assay on its own.

Your Thoughts?
How do you diagnose patients with CDI in your practice? Join the discussion by posting a comment.