Choosing C. difficile Diagnostics Wisely

Improper diagnosis of C. difficile can lead to patient harm

C. difficile diagnosis can be challenging. It is possible to be a carrier of C. difficile, meaning that the bacteria is present, but is not producing disease-causing toxins that make people sick.

It is important to properly differentiate people with a true C. difficile infection from C. difficile carriers. Treating C. difficile carriers may make people more susceptible to a true C. difficile infection. Antibiotic treatments for the initial infection may also be unnecessarily stopped.

There are three types of diagnostic tests for C. difficile :

Glutamate dehydrogenase (GDH) is the protein produced by all C. difficile bacteria, regardless of their toxin-producing ability. Testing for GDH is a good screening marker for C. difficile infection, but follow-up testing is necessary because we cannot tell from a GDH result alone if the strain can produce toxin, which makes patients sick. With a GDH-positive result alone, it is possible that the patient is simply a carrier.

Toxins A and B are produced by toxigenic strains of C. difficile and cause the symptoms of the infection. Toxin results more closely correlate to disease state and clinical outcomes than other testing options, but testing is not sensitive enough to be used as a standalone test.

Molecular (PCR) testing is a very sensitive method of identifying whether the C. difficile bacteria can make toxin but does not indicate whether toxin is actually present in the patient sample.

What do the guidelines say?

A 2023 update from SHEA/IDSA/APIC announced a proposed modification to the National Healthcare Safety Network’s (NHSN) C. difficile infection reporting guidelines. In the past, the last test of record defined a C. difficile infection reportable event. The proposed new C. difficile infection event definition includes any positive test and treatment initiated within 2 days of the positive C. difficile test.

This proposed change is significant because the order of testing in the C. difficile infection testing algorithm no longer impacts whether a positive C. difficile test is a reportable C. difficile infection event. This change encourages greater clinician discretion and provides laboratories more flexibility in selecting the algorithm that works best for their specific patient population and workflow.

Because so many people are C. difficile carriers, the Infectious Disease Society of America (IDSA), Society for Healthcare and Epidemiology of America (SHEA), the European Society of Clinical Microbiology and Infectious Diseases (ESCMID), and the American College of Gastroenterology (ACG) all suggest using a toxin test to help differentiate patients with active disease from those who are simply carriers.

Additional information

– The Importance of Toxin Testing
– Testing for C. difficile and its Disease
– C. difficile Infection: The challenge, tests, and guidelines

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