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  • Review Article
  • Published:

Clostridium difficile infection: epidemiology, diagnosis and understanding transmission

Nature Reviews Gastroenterology & Hepatology volume 13, pages 206–216 (2016)Cite this article

Subjects

Key Points

  • Clostridium difficile infection (CDI) is a continually evolving global health-care problem

  • Community-onset CDI is increasing and multiple potential reservoirs of infection exist including environmental sources, animals, asymptomatic patients and symptomatic patients

  • Highly discriminatory typing techniques such as whole-genome sequencing and multi-locus variable-number tandem-repeat analysis offer the potential for illuminating previously under-recognized routes of C. difficile transmission

  • The optimal approach to sampling and testing for CDI remains a contentious issue

  • Multi-step algorithms are recommended to improve diagnostic sensitivity and specificity

Abstract

Clostridium difficile infection (CDI) continues to affect patients in hospitals and communities worldwide. The spectrum of clinical disease ranges from mild diarrhoea to toxic megacolon, colonic perforation and death. However, this bacterium might also be carried asymptomatically in the gut, potentially leading to 'silent' onward transmission. Modern technologies, such as whole-genome sequencing and multi-locus variable-number tandem-repeat analysis, are helping to track C. difficile transmission across health-care facilities, countries and continents, offering the potential to illuminate previously under-recognized sources of infection. These typing strategies have also demonstrated heterogeneity in terms of CDI incidence and strain types reflecting different stages of epidemic spread. However, comparison of CDI epidemiology, particularly between countries, is challenging due to wide-ranging approaches to sampling and testing. Diagnostic strategies for C. difficile are complicated both by the wide range of bacterial targets and tests available and the need to differentiate between toxin-producing and non-toxigenic strains. Multistep diagnostic algorithms have been recommended to improve sensitivity and specificity. In this Review, we describe the latest advances in the understanding of C. difficile epidemiology, transmission and diagnosis, and discuss the effect of these developments on the clinical management of CDI.

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Figure 1: Model for Clostridium difficile acquisition, germination and infection.
Figure 2: Global epidemiology of common Clostridium difficile ribotypes.
Figure 3: Examples of multistep algorithms for testing stool samples for rapid diagnosis of CDI.

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Authors and Affiliations

  1. University of Leeds/Leeds Teaching Hospitals NHS Trust, Old Medical School, Leeds General Infirmary, Great George Street, Leeds, LS1 3EX, UK

    Jessica S. H. Martin & Mark H. Wilcox

  2. NIHR Biomedical Research Unit in Gastrointestinal and Liver Diseases, Nottingham University Hospitals NHS Trust, University of Nottingham, Derby Road, Nottingham, NG7 2UH, UK

    Tanya M. Monaghan

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  1. Jessica S. H. Martin
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Contributions

J.S.H.M. and T.M.M. researched data for the article. All authors contributed equally to discussion of content, writing and reviewing/editing the manuscript before submission.

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Correspondence to Mark H. Wilcox.

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Competing interests

M.H.W. declares grant and/or research support from Abbott, Actelion, Alere, Astellas, Biomerieux, Cerexa, Cubist, Da Volterra, European Tissue Symposium, Merck, Sanofi-Pasteur, Summit, The Medicines Company and Qiagen, which have funded research in the past 2 years. M.H.W. has received consultancies and/or lecture honoraria in the past 2 years from Actelion, Alere, Astellas, Astra-Zeneca, Basilea, Bayer, Cubist, Durata, European Tissue Symposium, Johnson & Johnson, Merck, Nabriva, Novacta, Novartis, Optimer, Pfizer, Roche, Sanofi-Pasteur and Seres. J.S.H.M. and T.M.M. declare no competing interests.

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Martin, J., Monaghan, T. & Wilcox, M. Clostridium difficile infection: epidemiology, diagnosis and understanding transmission. Nat Rev Gastroenterol Hepatol 13, 206–216 (2016). https://doi.org/10.1038/nrgastro.2016.25

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