Diagnostic Approaches for Clostridioides difficile Infection

Sample Collection and Selection

Testing should only be performed on unformed stool samples from symptomatic patients to avoid false positive results 3, 4
The Infectious Diseases Society of America recommends CDI testing on stool samples from all patients with infectious diarrhea who have negative tests for common enteropathogens 3
All patients with diarrhea who have been hospitalized for more than 72 hours should be tested for CDI, regardless of whether the physician specifically requested the test 3, 5
For patients with severe CDI complicated by ileus, perirectal swabs may provide an acceptable alternative with high sensitivity and specificity 4, 6

The Cell Culture Cytotoxicity Neutralization Assay is traditionally considered a reference standard for detecting C. difficile toxins directly in stool, with high sensitivity and specificity 1, 7
Toxigenic Culture allows recovery of isolates for epidemiological typing and characterization, and is more sensitive than CCNA but time-consuming 1, 7, 8
Enzyme Immunoassays for toxins A/B have high specificity but relatively low sensitivity, and are not recommended as a standalone test 4, 6
Nucleic Acid Amplification Tests detect C. difficile toxin genes directly from stool, with high sensitivity but potential to detect asymptomatic colonization 1, 4, 6, 7

A two-step testing approach is recommended, using a screening test such as GDH EIA or NAAT, followed by confirmation with toxin A/B EIA or another test 2, 3
The American College of Gastroenterology recommends using a two-step algorithm to increase the positive predictive value compared to single tests alone 2, 3

Clinical context is crucial for interpretation of test results, including recent antibiotic use, hospitalization history, and symptoms such as fever, abdominal pain, and leukocytosis 4, 6
Repeat testing after a first negative sample during the same diarrheal episode may be useful only in selected cases with ongoing clinical suspicion, particularly during an epidemic situation 4, 6

Using a single test alone, especially toxin EIA, which has limited sensitivity 1, 4
Failing to consider clinical context when interpreting test results, as positive tests may represent colonization rather than infection in some cases 1, 8