What does a positive Clostridiium difficile (C. diff) stool sample with a negative toxin result indicate?

From the Guidelines

A positive C. difficile stool sample with a negative toxin result indicates colonization rather than active infection, and treatment is typically not recommended unless the patient is showing symptoms of C. difficile infection. This is based on the most recent and highest quality study by Planche et al 1, which found that patients with a positive toxin test should be treated, while those who are positive by TC and/or NAAT alone could be considered “excretors” who may present an infection control risk but do not require treatment. The study also recommended using a multistep algorithm such as screening with GDH and confirming positives with a “sensitive” toxin A/B enzyme immunoassay, which has been national UK policy since 2012. Some key points to consider in this situation include:

• The presence of the bacteria without toxin production often represents non-pathogenic colonization or the presence of non-toxigenic strains.
• Many people, especially those in healthcare settings or who have recently taken antibiotics, can be colonized with C. difficile without developing illness.
• Unnecessary treatment of colonization can disrupt normal gut flora and potentially lead to antibiotic resistance.
• If symptoms are present despite the negative toxin test, healthcare providers might consider additional testing or empiric treatment based on clinical judgment, as false negatives can occur.
• The two-step testing process (detecting the organism and then testing for toxin) helps distinguish between colonization and active infection, as supported by the study by Polage et al 1, which found that the toxin-positive/PCR-positive group had more diarrhea and longer duration of diarrhea, more prior antibiotic exposure, and more patients with leukocytosis.

From the Research

Interpretation of C. diff Stool Sample Results

A positive Clostridiium difficile (C. diff) stool sample with a negative toxin result can be interpreted in several ways:

• The presence of C. diff in the stool sample indicates that the patient is colonized with the bacteria, but the absence of detectable toxin suggests that the bacteria may not be actively producing toxin 2.
• A study found that over half of the patients with a positive C. diff stool sample and negative toxin result were actually infected with toxigenic C. difficile, suggesting that the toxin result may be a false negative 2.
• The clinical significance of a positive C. diff stool sample with a negative toxin result is unclear, and further research is needed to determine the optimal approach to diagnosis and treatment 3, 4.
• It is possible that the patient may be an asymptomatic carrier of C. diff, as the bacteria can be carried as normal gastrointestinal flora, especially in adults who have received antibiotic therapy 5.

Clinical Implications

The clinical implications of a positive C. diff stool sample with a negative toxin result are:

• The patient may still be at risk of developing C. diff infection, even if the toxin result is negative 2.
• The patient may be potentially infectious, even if the toxin result is negative, as the presence of C. diff in the stool sample indicates that the bacteria are present 4.
• The optimal approach to treatment and management of patients with a positive C. diff stool sample and negative toxin result is unclear, and further research is needed to determine the best course of action 3.