Clostridioides difficile (C. diff) is a bacterium that causes severe diarrhea and colon inflammation (colitis). It produces toxins, primarily toxin A and toxin B, responsible for infection symptoms. Detecting these toxins in a stool sample is central to diagnosing an active C. diff infection.
Understanding C. diff Toxin Testing
Diagnosing C. diff infection typically involves analyzing a stool sample. Different tests target distinct aspects of the bacterium. Enzyme immunoassay (EIA) tests directly identify the presence of C. diff toxins (A and B) in stool. A positive EIA test indicates active toxin production, usually associated with symptomatic infection. These tests offer rapid results but may be less sensitive.
Polymerase chain reaction (PCR) tests detect the genetic material (DNA) of C. diff bacteria, including genes for toxin production. PCR tests are highly sensitive, detecting even small amounts of bacterial DNA. However, a positive PCR test indicates the presence of the toxigenic bacterium but does not confirm active toxin production or ongoing infection. This is because it can detect dead bacterial fragments or the organism in an asymptomatic state. Some laboratories also use glutamate dehydrogenase (GDH) tests, which detect a bacterial antigen present in both toxin-producing and non-toxin-producing C. diff strains, often as a screening step.
Why Toxin Positivity Lingers
Even after successful treatment and symptom resolution, C. diff toxins can remain detectable in stool. This persistence is due to the slow clearance of bacterial components and residual toxins from the gut. Highly sensitive diagnostic tests, particularly PCR, contribute to this, as they can detect bacterial DNA even when the organism is no longer actively causing disease. PCR tests, for instance, can remain positive for up to eight weeks after treatment, even if the patient is symptom-free.
Another factor is asymptomatic colonization, where individuals carry C. diff bacteria and may produce toxins without experiencing any symptoms. In these cases, detectable toxin does not signify an active infection requiring treatment. This lingering positivity highlights a difference between simply carrying the bacteria or its products and having an active, symptomatic infection.
What Persistent Toxin Positivity Means
When a C. diff toxin test remains positive after treatment or symptom resolution, it typically indicates colonization, especially if symptoms are absent. Asymptomatic individuals testing positive for C. diff toxins generally do not require further treatment. The presence of the organism or its toxins in the absence of diarrhea or other symptoms is considered asymptomatic carriage.
Distinguishing between active infection and colonization is important for patient management. Active infection requires both the presence of toxigenic bacteria or its toxins and clinical symptoms like diarrhea. Asymptomatic carriers, even if toxin-positive, usually do not experience illness and are less likely to transmit the infection than symptomatic individuals. A patient’s clinical presentation should guide treatment decisions, not solely a positive test result.
When to Retest for C. diff
Routine retesting for C. diff toxin after successful treatment, often called a “test of cure,” is generally not recommended. C. diff toxins or bacterial DNA can persist in stool for weeks after symptoms resolve, leading to positive results that do not reflect active disease. Such retesting can cause unnecessary anxiety and lead to inappropriate antibiotic treatment.
Retesting is indicated only if symptoms recur after initial treatment. If diarrhea and other symptoms return, testing can help confirm a C. diff recurrence or another cause. Healthcare providers prioritize monitoring symptom resolution as the primary indicator of successful treatment, emphasizing that clinical signs and symptoms, not a negative test result, should guide patient care.