Davies, KA orcid.org/0000-0001-6862-5355, Planche, T and Wilcox, MH orcid.org/0000-0002-4565-2868 (2018) The predictive value of quantitative nucleic acid amplification detection of Clostridium difficile toxin gene for faecal sample toxin status and patient outcome. PLOS ONE, 13 (12). e0205941. ISSN 1932-6203
Abstract
Background: Laboratory diagnosis of Clostridium difficile infection (CDI) remains unsettled, despite updated guidelines. We investigated the potential utility of quantitative data from a nucleic acid amplification test (NAAT) for C. difficile toxin gene (tg) for patient management.
Methods: Using data from the largest ever C. difficile diagnostic study (8853 diarrhoeal samples from 7335 patients), we determined the predicative value of C. difficile tgNAAT (Cepheid Xpert C.diff) low cycle threshold (CT) value for patient toxin positive status, CDI severity, mortality and CDI recurrence. Reference methods for CDI diagnosis were cytotoxicity assay (CTA) and cytotoxigenic culture (CTC).
Results: Of 1281 tgNAAT positive faecal samples, 713 and 917 were CTA and CTC positive, respectively. The median tgNAAT CT for patients who died was 25.5 vs 27.5 for survivors (p = 0.021); for toxin-positivity was 24.9 vs 31.6 for toxin-negative samples (p<0.001) and for patients with a recurrence episode was 25.6 vs 27.3 for those who did not have a recurrent episode (p = 0.111). Following optimal cut-off determination, low CT was defined as ≤25 and was significantly associated with a toxin-positive result (P<0.001, positive predictive value 83.9%), presence of PCR-ribotype 027 (P = 0.025), and mortality (P = 0.032). Recurrence was not associated with low CT (p 0.111).
Conclusions: Low tgNAAT CT could indicate CTA positive patients, have more severe infection, increased risk of mortality and possibly recurrence. Although, the limited specificity of tgNAAT means it cannot be used as a standalone test, it could augment a more timely diagnosis, and optimise management of these at-risk patients.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2018 Davies et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Molecular Gastroenterology (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 08 Jan 2019 15:47 |
Last Modified: | 08 Jan 2019 15:47 |
Status: | Published |
Publisher: | Public Library of Science |
Identification Number: | 10.1371/journal.pone.0205941 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:140654 |