What are the next steps for a patient with a positive Clostridioides difficile (C. diff) glutamate dehydrogenase (GDH) test and negative C. diff toxin A and B tests?

From the Guidelines

The next steps for a patient with a positive C. difficile glutamate dehydrogenase (GDH) test but negative toxin A&B test would be to perform a nucleic acid amplification test (NAAT) to confirm the diagnosis, as recommended by the most recent guidelines 1. This discordant result indicates the presence of C. difficile bacteria (detected by GDH) but without detectable toxin production. The use of a two-step approach, with a second test in case of a positive first test, is supported by the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) 1, which suggests that a low positive predictive value (PPV) is associated with unnecessary treatment of non-infected patients. If the NAAT is positive, treat the patient only if they have symptoms of C. difficile infection such as diarrhea, abdominal pain, or fever. For symptomatic patients with confirmed infection, oral vancomycin 125 mg four times daily for 10 days or fidaxomicin 200 mg twice daily for 10 days would be appropriate first-line treatments. If the NAAT is negative or the patient is asymptomatic, no antibiotic treatment is needed as this likely represents colonization rather than active infection. During evaluation, it's essential to discontinue unnecessary antibiotics and proton pump inhibitors if possible, as these can increase the risk of developing active infection, as highlighted in the clinical practice guideline for the evaluation of fever and infection in older adult residents of long-term care facilities 1. Implement contact precautions for symptomatic patients to prevent transmission, and consider alternative causes for the patient's symptoms if C. difficile infection is not confirmed. Additionally, consider the use of faecal microbiota transplant as treatment for recurrent or refractory Clostridioides difficile infection, as recommended by the joint British Society of Gastroenterology (BSG) and Healthcare Infection Society (HIS) guidelines 1.

From the FDA Drug Label

The FDA drug label does not answer the question.

From the Research

Next Steps for CDIFF GDH Positive and Toxin A&B Negative Results

• The patient has tested positive for Clostridium difficile (CDIFF) glutamate dehydrogenase (GDH) antigen but negative for toxin A&B, which can be a challenging result to interpret 2.
• Studies have shown that over half of the patients with GDH positive/toxin negative results may be infected with toxigenic C. difficile, highlighting the importance of further testing 2.
• A retrospective study found that 63.2% of GDH positive/toxin negative patients had toxigenic C. difficile recovered from their fecal specimens, suggesting that these patients may still be at risk of CDIFF infection 2.
• The use of nucleic acid amplification tests (NAATs) or toxigenic culture can help confirm the diagnosis of CDIFF infection in patients with GDH positive/toxin negative results 3, 4.
• Diagnostic algorithms that utilize simultaneous detection kits for GDH and toxin A/B as an initial screening test, followed by confirmatory testing for discrepant results, may be useful for accurate and efficient diagnosis of CDI 5.
• Rapid tests for GDH detection have been shown to be suitable for CDI diagnosis as screening tests and may also be used as a single method in some cases 6.

Considerations for Further Testing

• The decision to perform further testing should be based on the patient's clinical presentation, medical history, and risk factors for CDIFF infection 2, 3.
• The use of Bayesian simulation and likelihood ratios can help determine the probability of CDIFF infection in patients with GDH positive/toxin negative results 3.
• The sensitivity and specificity of different diagnostic tests, including GDH and toxin A/B enzyme immunoassays, should be considered when interpreting test results 4, 5, 6.

Clinical Implications

• Patients with GDH positive/toxin negative results should be closely monitored for signs and symptoms of CDIFF infection, and further testing should be performed as needed 2, 3.
• The detection of GDH antigen can help identify patients at risk of CDIFF infection, even if toxin A&B is not detected 2, 6.
• The use of diagnostic algorithms that incorporate multiple tests and clinical evaluation can help improve the accuracy and efficiency of CDI diagnosis 5.