Journal Of Clinical Microbiology | June 13, 2018

Banz A, Lantz A, Riou B, Foussadier A, Miller M, Davies K and Wilcox M

Journal of Clinical Microbiology

DOI: 10.1128/JCM.00452-18

This study was peformed using a Simoa® Homebrew assay.

Background: Guidelines recommend the use of an algorithm for the laboratory diagnosis of Clostridium difficile infection (CDI). Enzyme immunoassays (EIAs) detecting C. difficile (CD) toxins cannot be used as standalone tests due to sub-optimal sensitivity and molecular tests suffer from non-specificity by detecting colonization. Sensitive immunoassays have recently been developed to improve and simplify CDI diagnosis.

Methods: Assays detecting CD toxins have been developed using single molecule array technology (SIMOA). SIMOA performance was assessed relative to a laboratory case definition of CDI defined by positive GDH screen and cell cytotoxicity neutralizing assay (CCNA). Samples were tested with SIMOA assays and a commercial toxin EIA to compare performance, with discrepancy resolution using a commercial nucleic acid-based test and a second cell cytotoxicity assay.

Results: The SIMOA toxin A and B assays showed limits of detection of 0.6 and 2.9 pg/ml and intra-assay coefficients of variation below 10%. The optimal clinical thresholds for the toxin A and B assays were determined to be 22.1 and 18.8 pg/ml with resultant sensitivities of 84.8 and 95.5%. By contrast, a high performing EIA toxin test had a sensitivity of 71.2%. Thus, the SIMOA assays detected toxins in 24% more samples with laboratory-defined CDI than the high performing toxin EIA (95%: 63/66 versus 71%: 47/66 ).

Conclusions: This study shows that SIMOA CD toxin assays have a higher sensitivity than currently available toxin EIA and have the potential to improve CDI diagnosis.