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Rapid, accurate, and on-site detection of C. difficile in stool samples

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Bomers, Marije K., Menke, Frederik P., Savage, Richard S., Vandenbroucke-Grauls, Christina M. J. E., van Agtmael, Michiel A., Covington, James A. and Smulders, Yvo M. (2015) Rapid, accurate, and on-site detection of C. difficile in stool samples. The American Journal of Gastroenterology, 110 (4). pp. 588-594. doi:10.1038/ajg.2015.90 ISSN 0002-9270.

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Official URL: http://dx.doi.org/10.1038/ajg.2015.90

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Abstract

OBJECTIVES:

A rapid test to diagnose Clostridium difficile infection (CDI) on hospital wards could minimize common but critical diagnostic delay. Field asymmetric ion mobility spectrometry (FAIMS) is a portable mass spectrometry instrument that quickly analyses the chemical composition of gaseous mixtures (e.g., above a stool sample). Can FAIMS accurately distinguish C. difficile-positive from -negative stool samples?

METHODS:

We analyzed 213 stool samples with FAIMS, of which 71 were C. difficile positive by microbiological analysis. The samples were divided into training, test, and validation samples. We used the training and test samples (n=135) to identify which sample characteristics discriminate between positive and negative samples, and to build machine learning algorithms interpreting these characteristics. The best performing algorithm was then prospectively validated on new, blinded validation samples (n=78). The predicted probability of CDI (as calculated by the algorithm) was compared with the microbiological test results (direct toxin test and culture).

RESULTS:

Using a Random Forest classification algorithm, FAIMS had a high discriminatory ability on the training and test samples (C-statistic 0.91 (95% confidence interval (CI): 0.86–0.97)). When applied to the blinded validation samples, the C-statistic was 0.86 (0.75–0.97). For samples analyzed ≤7 days of collection (n=76), diagnostic accuracy was even higher (C-statistic: 0.93 (0.85–1.00)). A cutoff value of 0.32 for predicted probability corresponded with a sensitivity of 92.3% (95% CI: 77.4–98.6%) and specificity of 86.0% (78.3–89.3%). For even fresher samples, discriminatory ability further increased.

CONCLUSIONS:

FAIMS analysis of unprocessed stool samples can differentiate between C. difficile-positive and -negative samples with high diagnostic accuracy.

Item Type: Journal Article
Subjects: Q Science > QD Chemistry
R Medicine > RC Internal medicine
Divisions: Faculty of Science, Engineering and Medicine > Engineering > Engineering
Library of Congress Subject Headings (LCSH): Clostridium difficile, Clostridium diseases -- Diagnosis, Field ionization mass spectrometry
Journal or Publication Title: The American Journal of Gastroenterology
Publisher: Nature Publishing Group
ISSN: 0002-9270
Official Date: April 2015
Dates:
DateEvent
April 2015Published
21 March 2015Available
4 February 2015Accepted
Volume: 110
Number: 4
Page Range: pp. 588-594
DOI: 10.1038/ajg.2015.90
Status: Peer Reviewed
Publication Status: Published
Access rights to Published version: Restricted or Subscription Access

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