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Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection.

Planche, TD; Davies, KA; Coen, PG; Finney, JM; Monahan, IM; Morris, KA; O'Connor, L; Oakley, SJ; Pope, CF; Wren, MW; et al. Planche, TD; Davies, KA; Coen, PG; Finney, JM; Monahan, IM; Morris, KA; O'Connor, L; Oakley, SJ; Pope, CF; Wren, MW; Shetty, NP; Crook, DW; Wilcox, MH (2013) Differences in outcome according to Clostridium difficile testing method: a prospective multicentre diagnostic validation study of C difficile infection. Lancet Infectious Diseases, 13 (11). pp. 936-945. ISSN 1474-4457 https://doi.org/10.1016/S1473-3099(13)70200-7
SGUL Authors: Monahan, Irene Margaret Planche, Timothy David

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Abstract

BACKGROUND: Diagnosis of Clostridium difficile infection is controversial because of many laboratory methods, compounded by two reference methods. Cytotoxigenic culture detects toxigenic C difficile and gives a positive result more frequently (eg, because of colonisation, which means that individuals can have the bacterium but no free toxin) than does the cytotoxin assay, which detects preformed toxin in faeces. We aimed to validate the reference methods according to clinical outcomes and to derive an optimum laboratory diagnostic algorithm for C difficile infection. METHODS: In this prospective, multicentre study, we did cytotoxigenic culture and cytotoxin assays on 12,420 faecal samples in four UK laboratories. We also performed tests that represent the three main targets for C difficile detection: bacterium (glutamate dehydrogenase), toxins, or toxin genes. We used routine blood test results, length of hospital stay, and 30-day mortality to clinically validate the reference methods. Data were categorised by reference method result: group 1, cytotoxin assay positive; group 2, cytotoxigenic culture positive and cytotoxin assay negative; and group 3, both reference methods negative. FINDINGS: Clinical and reference assay data were available for 6522 inpatient episodes. On univariate analysis, mortality was significantly higher in group 1 than in group 2 (72/435 [16·6%] vs 20/207 [9·7%], p=0·044) and in group 3 (503/5880 [8·6%], p<0·001), but not in group 2 compared with group 3 (p=0·4). A multivariate analysis accounting for potential confounders confirmed the mortality differences between groups 1 and 3 (OR 1·61, 95% CI 1·12-2·31). Multistage algorithms performed better than did standalone assays. INTERPRETATION: We noted no increase in mortality when toxigenic C difficile alone was present. Toxin (cytotoxin assay) positivity correlated with clinical outcome, and so this reference method best defines true cases of C difficile infection. A new diagnostic category of potential C difficile excretor (cytotoxigenic culture positive but cytotoxin assay negative) could be used to characterise patients with diarrhoea that is probably not due to C difficile infection, but who can cause cross-infection.

Item Type: Article
Additional Information: Creative Commons Attribution License (CC BY) This article is available under the terms of the Creative Commons Attribution License (CC BY) https://creativecommons.org/licenses/by/4.0/ You may copy and distribute the article, create extracts, abstracts and new works from the article, alter and revise the article, text or data mine the article and otherwise reuse the article commercially (including reuse and/or resale of the article) without permission from Elsevier. You must give appropriate credit to the original work, together with a link to the formal publication through the relevant DOI and a link to the Creative Commons user license above. You must indicate if any changes are made but not in any way that suggests the licensor endorses you or your use of the work. Permission is not required for this type of reuse.
Keywords: Adolescent, Adult, Aged, Area Under Curve, Child, Child, Preschool, Clostridium difficile, DNA, Bacterial, Diarrhea, Enterocolitis, Pseudomembranous, Enterotoxins, Feces, Female, Glutamate Dehydrogenase, Humans, Logistic Models, Male, Middle Aged, Polymerase Chain Reaction, Predictive Value of Tests, Prospective Studies, ROC Curve, Sensitivity and Specificity, Young Adult, Feces, Humans, Clostridium difficile, Enterocolitis, Pseudomembranous, Diarrhea, Glutamate Dehydrogenase, DNA, Bacterial, Enterotoxins, Area Under Curve, Logistic Models, Sensitivity and Specificity, Prospective Studies, Predictive Value of Tests, ROC Curve, Polymerase Chain Reaction, Adolescent, Adult, Aged, Middle Aged, Child, Child, Preschool, Female, Male, Young Adult, Science & Technology, Life Sciences & Biomedicine, Infectious Diseases, INFECTIOUS DISEASES, GLUTAMATE-DEHYDROGENASE, LABORATORY DIAGNOSIS, TOXIN, DIARRHEA, DISEASE, ALGORITHM, CULTURE, GUIDELINES, MORTALITY, STRAIN, Microbiology, 1103 Clinical Sciences, 1108 Medical Microbiology
SGUL Research Institute / Research Centre: Academic Structure > Infection and Immunity Research Institute (INII)
Journal or Publication Title: Lancet Infectious Diseases
ISSN: 1474-4457
Language: eng
Dates:
DateEvent
November 2013Published
3 September 2013Published Online
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
UNSPECIFIEDDepartment of HealthUNSPECIFIED
PubMed ID: 24007915
Web of Science ID: WOS:000325956000031
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URI: https://openaccess.sgul.ac.uk/id/eprint/103664
Publisher's version: https://doi.org/10.1016/S1473-3099(13)70200-7

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