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1088. Ultrasensitive Detection of C. difficile Toxins in Stool Using Single Molecule Counting Technology: A Multicenter Study for Evaluation of Clinical Performance

BACKGROUND: Commercially available tests for Clostridium difficile infection (CDI) make test selection by the laboratory difficult due to the following unsatisfactory characteristics: long turnaround time, poor sensitivity, and/or poor specificity. The Singulex Clarity(®) C. diff toxins A/B assay (i...

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Autores principales: Young, Stephen, Mills, Ray, Griego-Fullbright, Christen, Wagner, Aaron, Herding, Emily, Nordberg, Vickie, Friedland, Emily, Bartolome, Amelita, Almazan, Anna, Tam, Stanley, Biscocho, Sheryl, Abusali, Salina, Sandlund, Johanna, Estis, Joel, Bishop, Jeffrey, Hansen, Glen
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255500/
http://dx.doi.org/10.1093/ofid/ofy210.923
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author Young, Stephen
Mills, Ray
Griego-Fullbright, Christen
Wagner, Aaron
Herding, Emily
Nordberg, Vickie
Friedland, Emily
Bartolome, Amelita
Almazan, Anna
Tam, Stanley
Biscocho, Sheryl
Abusali, Salina
Sandlund, Johanna
Estis, Joel
Bishop, Jeffrey
Hansen, Glen
author_facet Young, Stephen
Mills, Ray
Griego-Fullbright, Christen
Wagner, Aaron
Herding, Emily
Nordberg, Vickie
Friedland, Emily
Bartolome, Amelita
Almazan, Anna
Tam, Stanley
Biscocho, Sheryl
Abusali, Salina
Sandlund, Johanna
Estis, Joel
Bishop, Jeffrey
Hansen, Glen
author_sort Young, Stephen
collection PubMed
description BACKGROUND: Commercially available tests for Clostridium difficile infection (CDI) make test selection by the laboratory difficult due to the following unsatisfactory characteristics: long turnaround time, poor sensitivity, and/or poor specificity. The Singulex Clarity(®) C. diff toxins A/B assay (in development) is a rapid and automated immunoassay for the detection of C. difficile toxins A and B in stool, with analytical limits of detection for toxins A and B at 2.0 and 0.7 pg/mL, respectively. In this multicenter study, the clinical performance of the Singulex Clarity C. diff toxins A/B assay was compared with standalone PCR, a multistep algorithm with enzyme immunoassay (EIA) and PCR, and cell cytotoxicity neutralization assay (CCNA). METHODS: Fresh samples from 267 subjects with suspected CDI were tested at two sites (Minneapolis Medical Research Foundation and TriCore Reference Laboratories) with the Singulex Clarity assay, PCR (Xpert(®)C. difficile), and EIA (C. Diff Quik Chek Complete(®)) for GDH and toxin testing. The performance of the assays and multistep algorithms were evaluated against CCNA (Microbiology Specialists, Inc.). RESULTS: The overall CDI prevalence was 15.7%. The Singulex Clarity C. diff toxins A/B assay had 90.5% sensitivity and 96.0% specificity, with a 98.2% negative predictive value when compared with CCNA, and the Clarity assay’s AuROC was 0.9534. PCR had 90.5% sensitivity and 91.1% specificity. Compared with CCNA, the toxin EIA had 47.6% sensitivity and 100% specificity. Testing with a multistep algorithm using EIA with discordant results reflexed to PCR resulted in 85.7% sensitivity and 94.7% specificity. CONCLUSION: The ultrasensitive Singulex Clarity C. diff toxins A/B assay is equivalent to the sensitivity of PCR while providing higher specificity. Compared with a multistep algorithm, the Clarity assay provides higher sensitivity and specificity while providing faster time-to-result in a simpler-to-understand, one-step reporting structure, allowing for a standalone, single-step solution for detection of C. difficile toxins in patients with suspected CDI. DISCLOSURES: E. Friedland, Singulex, Inc.: Employee, Salary. A. Bartolome, Singulex, Inc.: Employee, Salary. A. Almazan, Singulex, Inc.: Employee, Salary. S. Tam, Singulex, Inc.: Employee, Salary. S. Biscocho, Singulex, Inc.: Employee, Salary. S. Abusali, Singulex, Inc.: Employee, Salary. J. Sandlund, Singulex, Inc.: Employee, Salary. J. Estis, Singulex, Inc.: Employee, Salary. J. Bishop, Singulex, Inc.: Employee, Salary.
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spelling pubmed-62555002018-11-28 1088. Ultrasensitive Detection of C. difficile Toxins in Stool Using Single Molecule Counting Technology: A Multicenter Study for Evaluation of Clinical Performance Young, Stephen Mills, Ray Griego-Fullbright, Christen Wagner, Aaron Herding, Emily Nordberg, Vickie Friedland, Emily Bartolome, Amelita Almazan, Anna Tam, Stanley Biscocho, Sheryl Abusali, Salina Sandlund, Johanna Estis, Joel Bishop, Jeffrey Hansen, Glen Open Forum Infect Dis Abstracts BACKGROUND: Commercially available tests for Clostridium difficile infection (CDI) make test selection by the laboratory difficult due to the following unsatisfactory characteristics: long turnaround time, poor sensitivity, and/or poor specificity. The Singulex Clarity(®) C. diff toxins A/B assay (in development) is a rapid and automated immunoassay for the detection of C. difficile toxins A and B in stool, with analytical limits of detection for toxins A and B at 2.0 and 0.7 pg/mL, respectively. In this multicenter study, the clinical performance of the Singulex Clarity C. diff toxins A/B assay was compared with standalone PCR, a multistep algorithm with enzyme immunoassay (EIA) and PCR, and cell cytotoxicity neutralization assay (CCNA). METHODS: Fresh samples from 267 subjects with suspected CDI were tested at two sites (Minneapolis Medical Research Foundation and TriCore Reference Laboratories) with the Singulex Clarity assay, PCR (Xpert(®)C. difficile), and EIA (C. Diff Quik Chek Complete(®)) for GDH and toxin testing. The performance of the assays and multistep algorithms were evaluated against CCNA (Microbiology Specialists, Inc.). RESULTS: The overall CDI prevalence was 15.7%. The Singulex Clarity C. diff toxins A/B assay had 90.5% sensitivity and 96.0% specificity, with a 98.2% negative predictive value when compared with CCNA, and the Clarity assay’s AuROC was 0.9534. PCR had 90.5% sensitivity and 91.1% specificity. Compared with CCNA, the toxin EIA had 47.6% sensitivity and 100% specificity. Testing with a multistep algorithm using EIA with discordant results reflexed to PCR resulted in 85.7% sensitivity and 94.7% specificity. CONCLUSION: The ultrasensitive Singulex Clarity C. diff toxins A/B assay is equivalent to the sensitivity of PCR while providing higher specificity. Compared with a multistep algorithm, the Clarity assay provides higher sensitivity and specificity while providing faster time-to-result in a simpler-to-understand, one-step reporting structure, allowing for a standalone, single-step solution for detection of C. difficile toxins in patients with suspected CDI. DISCLOSURES: E. Friedland, Singulex, Inc.: Employee, Salary. A. Bartolome, Singulex, Inc.: Employee, Salary. A. Almazan, Singulex, Inc.: Employee, Salary. S. Tam, Singulex, Inc.: Employee, Salary. S. Biscocho, Singulex, Inc.: Employee, Salary. S. Abusali, Singulex, Inc.: Employee, Salary. J. Sandlund, Singulex, Inc.: Employee, Salary. J. Estis, Singulex, Inc.: Employee, Salary. J. Bishop, Singulex, Inc.: Employee, Salary. Oxford University Press 2018-11-26 /pmc/articles/PMC6255500/ http://dx.doi.org/10.1093/ofid/ofy210.923 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of Infectious Diseases Society of America. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Abstracts
Young, Stephen
Mills, Ray
Griego-Fullbright, Christen
Wagner, Aaron
Herding, Emily
Nordberg, Vickie
Friedland, Emily
Bartolome, Amelita
Almazan, Anna
Tam, Stanley
Biscocho, Sheryl
Abusali, Salina
Sandlund, Johanna
Estis, Joel
Bishop, Jeffrey
Hansen, Glen
1088. Ultrasensitive Detection of C. difficile Toxins in Stool Using Single Molecule Counting Technology: A Multicenter Study for Evaluation of Clinical Performance
title 1088. Ultrasensitive Detection of C. difficile Toxins in Stool Using Single Molecule Counting Technology: A Multicenter Study for Evaluation of Clinical Performance
title_full 1088. Ultrasensitive Detection of C. difficile Toxins in Stool Using Single Molecule Counting Technology: A Multicenter Study for Evaluation of Clinical Performance
title_fullStr 1088. Ultrasensitive Detection of C. difficile Toxins in Stool Using Single Molecule Counting Technology: A Multicenter Study for Evaluation of Clinical Performance
title_full_unstemmed 1088. Ultrasensitive Detection of C. difficile Toxins in Stool Using Single Molecule Counting Technology: A Multicenter Study for Evaluation of Clinical Performance
title_short 1088. Ultrasensitive Detection of C. difficile Toxins in Stool Using Single Molecule Counting Technology: A Multicenter Study for Evaluation of Clinical Performance
title_sort 1088. ultrasensitive detection of c. difficile toxins in stool using single molecule counting technology: a multicenter study for evaluation of clinical performance
topic Abstracts
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6255500/
http://dx.doi.org/10.1093/ofid/ofy210.923
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