From the Guidelines
C. difficile toxin tests are preferred over antigen tests for diagnosing Clostridioides difficile infection because they directly detect the toxins that cause clinical symptoms, providing better specificity for active disease. The antigen test detects glutamate dehydrogenase (GDH), which is present in all C. difficile strains regardless of toxin production, making it highly sensitive but not specific for active infection 1. In contrast, toxin tests, such as enzyme immunoassays (EIAs) or cell cytotoxicity neutralization assays (CCNAs), directly detect toxins A and B, which are responsible for the clinical symptoms of C. difficile infection 1.
Key Differences Between Antigen and Toxin Tests
- Antigen tests detect GDH, which is present in all C. difficile strains, regardless of toxin production
- Toxin tests detect toxins A and B, which cause clinical symptoms of C. difficile infection
- Antigen tests are highly sensitive but not specific for active infection
- Toxin tests are more specific for active disease but may be less sensitive than antigen tests
Clinical Practice Recommendations
- Use a two-step algorithm: antigen test screens for C. difficile presence, and if positive, toxin test confirms whether the strain is toxigenic and likely causing disease 1
- A positive antigen with negative toxin result may indicate colonization without active infection
- Positive results for both suggest active C. difficile infection requiring treatment
- Toxin test results more accurately correlate with clinical disease, despite potentially being available more slowly than antigen test results 1
From the Research
C. diff Antigen vs Toxin
- The detection of C. diff toxins is crucial for the diagnosis of Clostridium difficile infection (CDI) 2.
- Laboratory tests for CDI can detect either the organisms or its toxins, including toxigenic culture, glutamate dehydrogenase detection, nucleic acid amplification testing, cell cytotoxicity assay, and enzyme immunoassay towards toxin A and/or B 2.
- Toxin detection kits are commonly used for the diagnosis of CDI, with varying sensitivities and specificities, such as Meridian Premier, TechLab Tox A/B II, and BioMérieux VIDAS 3.
- The positive predictive value of these assays can be low if the prevalence of C. diff toxins in stool samples is relatively low, highlighting the need for a two-stage testing strategy 3.
Treatment of CDI
- Vancomycin and metronidazole are commonly used antibiotics for the treatment of CDI, with vancomycin being superior for treating severe CDI 4.
- Fidaxomicin has been shown to be superior to metronidazole, vancomycin, or their combination for the treatment of initial episode, first recurrence, and non-severe CDI 5.
- The treatment of CDI depends on the severity of the disease, with oral vancomycin being the first choice for antibiotic treatment, and fidaxomicin being a good alternative, especially in patients at risk of relapse 6.
Diagnosis and Treatment
- The diagnosis of CDI is essential for patient management, infection control, and defining its epidemiology 3.
- The treatment of CDI should be guided by the severity of the disease, with a focus on preventing recurrence and promoting sustained clinical cure 6, 5.
- New therapeutic approaches, such as monoclonal antibodies and gut microbiota modulating therapies, are being developed and tested to achieve higher sustained clinical cure in CDI 6.