What does a negative Clostridioides difficile (C. diff) toxin test and a positive C. diff biofire (Biomerieux Biofire FilmArray) test result indicate?

From the Guidelines

The patient has a discrepancy in their Clostridioides difficile (C. diff) test results, with a negative toxin test but a positive BioFire PCR test, indicating C. diff colonization rather than active infection, and treatment decisions should be based on clinical symptoms. This situation is sometimes referred to as "C. diff colonization" rather than active infection, as the bacteria are present in the patient's gut but may not be actively producing toxins 1. The BioFire PCR test is more sensitive and can detect the genes for toxin production, while the toxin test detects the actual toxin proteins that cause disease.

According to the study by Planche et al, patients with a positive toxin test should be treated, while those who are positive by PCR alone could be considered "excretors" who may present an infection control risk but do not require treatment 1. The study also found that the combination of GDH immunoassay plus toxin EIA was almost identical in performance to CCNA, and recommended using a multistep algorithm such as screening with GDH and confirming positives with a sensitive toxin A/B enzyme immunoassay.

In terms of treatment, if the patient has diarrhea, abdominal pain, or other symptoms consistent with C. diff infection, treatment with oral vancomycin (125 mg four times daily for 10 days) or fidaxomicin (200 mg twice daily for 10 days) may be warranted despite the negative toxin test 1. However, if the patient has no symptoms, treatment is typically not necessary as many people can carry C. diff without illness.

Some key points to consider include:

• The patient's clinical symptoms should guide treatment decisions
• The discrepancy between the toxin test and BioFire PCR test results is due to the different methods of detection
• Patients with a positive toxin test should be treated, while those who are positive by PCR alone may not require treatment
• A multistep algorithm such as screening with GDH and confirming positives with a sensitive toxin A/B enzyme immunoassay may be useful in diagnosing C. diff infection.

It's also important to note that repeat testing for C. diff is not typically necessary, unless there is a change in the patient's clinical presentation or symptoms worsen 1. Additionally, empiric treatment without confirmatory testing is discouraged, as it may be unnecessary and potentially harmful to microbiome restoration.

From the Research

C. Diff Toxin Negative and C. Diff Biofire Positive

• A C. diff toxin negative and C. diff Biofire positive result can be confusing, but it's essential to understand what each test measures.
• The C. diff toxin test detects the presence of toxins produced by the C. difficile bacteria in the stool, which can cause disease 2.
• On the other hand, the Biofire test is a molecular test that detects the genetic material of the C. difficile bacteria, which can be present even if the bacteria are not producing toxins 3.
• A positive Biofire test and negative toxin test may indicate that the patient is a carrier of C. difficile, but not necessarily infected or producing toxins 3.
• Studies have shown that patients with a positive PCR (polymerase chain reaction) test, such as the Biofire test, and negative toxin test may not require treatment, as the risk of developing symptoms is low 3.

Clinical Implications

• The diagnosis of C. difficile infection (CDI) usually requires a multi-step diagnostic approach, including the C. difficile toxin test and the Biofire test 2.
• Clinicians should consider the patient's clinical presentation, medical history, and laboratory results when interpreting the test results 2.
• In some cases, a colonoscopy may be necessary to confirm the diagnosis of CDI, especially if the patient has a high clinical suspicion of disease with negative testing 2.

Treatment and Management

• The treatment of CDI depends on the severity of the disease and the patient's clinical presentation 3.
• Patients with a positive Biofire test and negative toxin test may not require treatment, but should be monitored for symptoms and have follow-up testing to ensure that the infection does not progress 3.
• Antibiotic treatment may be necessary for patients with severe CDI or those who are at high risk of developing complications 3.