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Is there a relationship between the presence of the binary toxin genes in Clostridium difficile strains and the severity of C. difficile infection (CDI)?

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Abstract

Some strains of Clostridium difficile produce a binary toxin, in addition to the main C. difficile virulence factors (toxins A and B). There have been conflicting reports regarding the role of binary toxin and its relationship to the severity of C. difficile infection (CDI). Samples, isolates and clinical data were collected as part of a prospective multicentre diagnostic study. Clostridium difficile isolates (n = 1259) were tested by polymerase chain reaction (PCR) assay to detect binary toxin genes cdtA and cdtB. The PCR binary toxin gene results were compared with clinical severity and outcome data, including 30-day all-cause mortality. The 1259 isolates corresponded to 1083 different patients (October 2010 to September 2011). The prevalence of binary toxin positive strains was significantly higher in faecal samples with detectable toxin A/B than in those without toxin but that were positive by cytotoxigenic culture (26.3% vs. 10.3%, p < 0.001). The presence of binary toxin correlated moderately with markers of CDI severity (white cell count, serum albumin concentration and serum creatinine concentration). However, the risk ratio for all-cause mortality was 1.68 for binary toxin positive patients and patients were significantly less likely to survive if they had CDI caused by a binary toxin gene positive strain, even after adjusting for age (p < 0.001). The presence of binary toxin genes does not predict the clinical severity of CDI, but it is significantly associated with the risk of all-cause mortality.

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Acknowledgements

This work has not been previously reported elsewhere. This work was supported by Health Education Yorkshire and the Humber and the Microbiology Department Research Funds, Leeds General Infirmary. We thank Warren Fawley for his assistance with assay optimisation and the hospitals involved in the initial data collection. We also thank the contributors to the previous study who performed the laboratory testing and clinical data collection: Timothy Planche, Pietro Coen, John Finney, Irene Monahan, Kirsti Morris, Lily O’Connor, Sarah Oakley, Cassie Pope, Mike Wren, Nandini Shetty and Derrick Crook.

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Authors and Affiliations

  1. Department of Microbiology, Leeds Teaching Hospitals NHS Trust and Healthcare Associated Infections Research Group, The University of Leeds, Old Medical School, Leeds, UK

    C. E. Berry, K. A. Davies & M. H. Wilcox

  2. Department of Microbiology, Leeds Teaching Hospitals NHS Trust, Leeds General Infirmary, Old Medical School, Leeds, LS1 3EX, UK

    K. A. Davies

  3. Leeds Institute of Health Sciences, The University of Leeds, Leeds, UK

    D. W. Owens

Authors
  1. C. E. Berry
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  2. K. A. Davies
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  3. D. W. Owens
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  4. M. H. Wilcox
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Contributions

The study was designed by CEB, MHW and KAD. CEB analysed the data and wrote the manuscript, in conjunction with KAD, DWO and MHW. All authors reviewed drafts of the manuscript.

Corresponding author

Correspondence to K. A. Davies.

Ethics declarations

Ethical approval

The study was approved by the National Research Ethics Service (reference number 10/H0715/34).

Informed consent

Informed consent was not required for this study, as approved by the National Research Ethics Service.

Data availability statement

The datasets analysed during the current study are available from the corresponding author on reasonable request.

Funding

This work was supported by Health Education Yorkshire and the Humber and the Microbiology Department Research Funds, Leeds General Infirmary.

Conflict of interest

C.E.B. has received research funding from bioMérieux and SUMMIT plc. K.A.D has received research funding from Astellas Pharma Europe Ltd., bioMérieux and Sanofi-Pasteur, and has received honorarium from Astellas Pharma Europe Ltd. and Summit. M.H.W. has received research support from Abbott, Actelion, Alere, Astellas, Biomerieux, Cerexa, Cubist, Da Volterra, European Tissue Symposium, Merck, Sanofi-Pasteur, Summit, The Medicines Company and Qiagen, has consultancies and/or lecture honoraria in the past 2 years from Actelion, Alere, Astellas, Astra-Zeneca, Basilea, Bayer, Cubist, Durata, European Tissue Symposium, J&J, Merck, Nabriva, Novacta, Novartis, Optimer, Pfizer, Roche, Sanofi-Pasteur and Seres, and is on the speakers’ bureau for Pfizer. D.W.O. has no conflicts of interest to declare.

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Berry, C.E., Davies, K.A., Owens, D.W. et al. Is there a relationship between the presence of the binary toxin genes in Clostridium difficile strains and the severity of C. difficile infection (CDI)?. Eur J Clin Microbiol Infect Dis 36, 2405–2415 (2017). https://doi.org/10.1007/s10096-017-3075-8

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  • DOI: https://doi.org/10.1007/s10096-017-3075-8

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