From the Guidelines
To test for Clostridium difficile, a stool toxin test as part of a multistep algorithm, such as glutamate dehydrogenase (GDH) plus toxin or NAAT plus toxin, is recommended rather than a nucleic acid amplification test (NAAT) alone, especially when there are preagreed institutional criteria for patient stool submission 1. This approach helps to balance the need for sensitive detection of the toxin-producing bacteria with the risk of false positives from colonization. The testing should only be done on unformed stools from symptomatic patients, as testing formed stools or asymptomatic individuals can lead to false positives. Some key points to consider in the testing process include:
- The initial test screens for glutamate dehydrogenase (GDH), a common enzyme produced by C. difficile.
- If the GDH test is positive, a second test is performed to detect toxins A and B, which cause the actual disease.
- Nucleic acid amplification tests (NAATs) like PCR can also be used, which detect the genes responsible for toxin production.
- Repeat testing within 7 days is not recommended if the initial test is negative, as this rarely changes management 1.
- Testing for cure after treatment is also not recommended since patients may continue to shed the organism even after symptoms resolve 1. It's also important to consider the clinical context, such as recent antibiotic use, hospitalization, and advanced age, when selecting patients for testing 1. Overall, the goal is to accurately diagnose C. difficile infection while minimizing the risk of false positives and unnecessary treatment.
From the Research
Testing Methods for Clostridium Difficile
There are several methods to test stool for Clostridium difficile, including:
- Enzyme immunoassay (EIA) for toxin A/B 2, 3
- EIA for glutamate dehydrogenase (GDH) 2, 3, 4
- Polymerase chain reaction (PCR)-based assay 2, 3, 4, 5
- Conventional PCR for detection of gluD, the glutamate dehydrogenase enzyme gene 5
- Toxigenic culture 4
- Multistep algorithmic approach 2, 4
Algorithm for Detection
A two-step algorithm is often used for the detection of Clostridium difficile, which includes:
- Screening for GDH by EIA or PCR 3, 4, 6
- Confirmation of positives by PCR or toxigenic culture 3, 4, 6
Performance of Tests
The performance of these tests varies, with:
- EIA for toxin A/B having a sensitivity of 39-67% and specificity of 94-100% 2, 3
- EIA for GDH having a sensitivity of 100% and specificity of 75-99.4% 2, 3, 4
- PCR-based assay having a sensitivity of 94-100% and specificity of 100% 2, 3, 4
- Conventional PCR for detection of gluD having a high sensitivity and specificity 5
Clinical Considerations
When testing for Clostridium difficile, it is essential to consider the clinical context, including: