GDH and toxin immunoassay for the diagnosis of Clostridioides (Clostridium) difficile infection is not a 'one size fit all' screening test.

Diagnosing Clostridioides (Clostridium) difficile infection is challenged by lack of a clear gold standard. We sought to determine if the two-step algorithm (screening GDH and toxin lateral flow assay followed by tcdB PCR) would have adequate clinical performance at a tertiary care center. Of 486 patients, 310 (63.8%) were immunocompromised. Of 150 PCR-positive specimens, 52 (34.7%) were toxin-positive and 126 (84.0%) were GDH positive. Positive GDH or toxin results corresponded to lower PCR cycle threshold values (P < 0.01). PCR-positive patients had more frequently documented antibiotic usage (78.4% vs 66.9%, P = 0.05) and diarrhea (91.0% vs. 79.4%, P < 0.01) and less frequent alternate etiologies of diarrhea (27.3% vs. 41.1%, P = 0.004) or laxative use (24.6% vs 36.1%, P = 0.02). Toxin positivity was associated with antibiotic use (P < 0.01), but not with neutropenia, diarrhea, malignancy, or chemotherapy (P > 0.05). The application of the 2-step algorithm should be thoroughly evaluated in immunocompromised patient populations before implementation.