The Laboratory Diagnosis of Clostridioides difficile Infection: An update of current laboratory practice

Clostridioides difficile can cause colitis and is associated with hospital acquired infections. The C. difficile infection (CDI) is due to production of toxins A and B which bind to epithelial cell surface receptors and triggers signaling pathways, leading to loss of epithelial barrier function, apoptosis, and inflammation, culminating in diarrheal disease. In early days, laboratory diagnosis of CDI was based on cell culture, identification of toxins, and their cytopathic effects. These assays were replaced by enzyme immunoassays for the detection of C. difficile toxins and the GDH house-keeping gene for improved specificity. Later, molecular assays with higher sensitivity were introduced which are becoming easier to incorporate into the test algorithm. The diagnosis of CDI and significance of laboratory results can be challenging with asymptomatic colonization of C. difficile in some patients. Test result interpretation is even more challenging due to multiple guidelines, emerging resistant C. difficile ribotypes, as well as differences in disease prevalence. An accurate test result for diagnosis of CDI depends on selecting patients with high pre-test probability, collecting an acceptable stool specimen, and a thorough understanding of current test methods.