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This document has been published as supplement to ESCMID's society journal Clinical Microbiology and Infection: Vol 22, S4, pages S63–S81, August 2016.


All details and links to the free full text in the chapter Medical Guidelines


This document has been published as supplement to ESCMID's society journal Clinical Microbiology and Infection: Vol 20, I s2, pages 1–26, March 2014.


All details and links to the free full text in the chapter Medical Guidelines

Els van Nood, Anne Vrieze, Max Nieuwdorp, Susana Fuentes, Erwin G. Zoetendal, Willem M. de Vos, Caroline E. Visser, Ed J. Kuijper, Joep F.W.M. Bartelsman, Jan G.P. Tijssen, Peter Speelman, Marcel G.W. Dijkgraaf, and Josbert J. Keller. N Engl J Med. 2013 Jan 16. [Epub ahead of print]

Free full text


ESCMID PGTW Anaerobes in Health and Disease

Jointly organised with the anaerobe infection group (ESGAI)

Szeged, Hungary, June 2012

Course material in the ESCMID OLL

Emergence and global spread of epidemic healthcare-associated Clostridium difficile

He M, Miyajima F, Roberts P, Ellison L, Pickard DJ, Martin MJ, Connor TR, Harris SR, Fairley D, Bamford KB, D'Arc S, Brazier J, Brown D, Coia JE, Douce G, Gerding D, Kim HJ, Koh TH, Kato H, Senoh M, Louie T, Michell S, Butt E, Peacock SJ, Brown NM, Riley T, Songer G, Wilcox M, Pirmohamed M, Kuijper E, Hawkey P, Wren BW, Dougan G, Parkhill J, Lawley TD. Nat Genet. 2012 Dec 9. doi: 10.1038/ng.2478. [Epub ahead of print]

PubMed abstract


CMI Theme Section


Still difficult; clinical practice guidelines for Clostrodium difficile infection

These ESCMID clinical guidelines concern diagnosis and management of CDI and CDAD.

CMI content are freely available for ESCMID members. Please log in or register.


ESGCD/ECDC medical guidelines

Infection control measures to limit the spread of Clostridium difficile.

Clin Microbiol Infect. 2008, 14(s5):1-24

Fluoroquinolone resistance in Clostridium difficile isolates from a prospective study of C. difficile infections in Europe.

Spigaglia P, Barbanti F, Mastrantonio P, Brazier JS, Barbut F, Delmée M, Kijper E, Poxton IR; ESCMID Study Group on Clostridium difficile (ESGCD). J Med Microbiol. 2008; 57:784-9

PubMed abstract

First confirmed cases of Clostridium difficile PCR ribotype 027 in Norway.

Update on epidemiology of C. difficile in Europe, March 10th, 2008  Ingebretsen A  Hansen C, Harmanus C, Kuijper EJ. Euro Surveill 2008;13(2)

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A case of Clostridium difficile-associated disease due to the highly virulent clone of Clostridium difficile PCR ribotype 027.

Zaiss NH, Weile J, Ackermann G, Kuijper E, Witte W, Nüebel U. March 2007 in Germany. Euro Surveill. 2007;12:E071115.1

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Prospective study of Clostridium difficile infections in Europe with phenotypic and genotypic characterisation of the isolates.

Barbut F, Mastrantonio P, Delmée M, Brazier J, Kuijper E, Poxton I; European Study Group on Clostridium difficile (ESGCD). Clin Microbiol Infect. 2007;13:1048-57.

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Update of Clostridium difficile-associated disease due to PCR ribotype 027 in Europe.

Kuijper EJ, Coignard B, Brazier JS, Suetens C, Drudy D, Wiuff C, Pituch H, Reichert P, Schneider F, Widmer AF, Olsen KE, Allerberger F, Notermans DW, Barbut F, Delmée M, Wilcox M, Pearson A, Patel BC, Brown DJ, Frei R, Akerlund T, Poxton IR, Tüll P. Euro Surveill. 2007 Jun 1;12(6):E1-2.

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Clostridium difficile: changing epidemiology and new treatment options.

Kuijper EJ, van Dissel JT, Wilcox MH. Curr Opin Infect Dis. 2007;20:376-83. Review

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First isolation of Clostridium difficile PCR ribotype 027 in Finland

Lyytikäinen O, Mentula S, Könönen E, Kotila S, Tarkka E, Anttila VJ, Mattila E, Kanerva M, Vaara M, Valtonen V. Euro Surveill. 2007 Nov 8;12(11):E071108.2

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Confirmed cases and report of clusters of severe infections due to Clostridium difficile PCR ribotype 027 in Germany

Kleinkauf N, Weiss B, Jansen A, Eckmanns T, Bornhofen B, Küehnen E, Weil HP, Michels H. Euro Surveill. 2007 Nov 15;12(11):E071115.2

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Characteristics and incidence of Clostridium difficile-associated disease in The Netherlands, 2005.

Paltansing S, van den Berg RJ, Guseinova RA, Visser CE, van der Vorm ER, Kuijper EJ. Clin Microbiol Infect. 2007:13:1058-64

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First isolation and report of clusters of Clostridium difficile PCR 027 cases in Ireland

Long S, Fenelon L, Fitzgerald S, Nolan N, Burns K, Hannan M, Kyne L, Fanning S, Drudy D. Euro Surveill. 2007 Apr 26;12(4):E070426.3

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Distribution of Clostridium difficile PCR ribotype 027 in British hospitals

Brazier JS, Patel B, Pearson A. Euro Surveill. 2007 Apr 26;12(4):E070426.2

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Spread and epidemiology of Clostridium difficile polymerase chain reaction ribotype 027/toxinotype III in The Netherlands.

Goorhuis A, Van der Kooi T, Vaessen N, Dekker FW, Van den Berg R, Harmanus C, van den Hof S, Notermans DW, Kuijper EJ. Clin Infect Dis. 2007;45:695-703

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Emergence of Clostridium difficile-associated diarrhoea in Europe.

Emergence of Clostridium difficile-associated diarrhoea in Europe (December 2007) Ed J. Kuijper, D. Notermans and I. Poxton, also on behalf of the ESCMID Study Group for Clostridium difficile (ESGCD)



ESGCD references for 2006

The collection of ESGCD references for 2006.


European surveillance of Clostridium difficile-associated disease

Presentation of Dr. Fred Barbut (Paris) at the ECCMID 2006, Nice on the European prospective study of Clostridium difficile strains: phenotypic and genotypic characterization of the isolates from different clinical status: interim results 
F. Barbut, P. Mastrantonio, M. Delmée, G. Ackermann, E. Bouza, C. Balmelli, D. Drudy, E. Kuijper, H. Ladas, E. Nagy, H. Pituch, M. Somolinos, E. Urban, M. Wullt, M. Yücesoy, M. Rupnik and I. Poxton for the  European Study Group on Clostridium difficile (ESGCD)


Emergence of Clostridium difficile-associated diarrhoea in Northern America and Europe

7 March 2006

Recently, a review has been published by ESGCD in collaboration with ECDC as a supplement of Clinical Microbiology and Infection (Kuijper EJ, Coignard B, Tüll P. Clin Microbiol. Infect 2006; 12: Suppl.6;2-18). Reprints are availaibe from Ed Kuijper.



J. Med. Microbiol., 2005, 54, Issue 2

Issue with selected papers presented at the First International Clostridium difficile Symposium (FICDS)

Journal website

Clostridium difficile (Editorial)

Ian R Poxton


Topics of this special issue:

  • Alternative treatments for Clostridium difficile disease: what really works?

    Lynne V McFarland

  • Revised nomenclature of Clostridium difficile toxins and associated genes

    Maja Rupnik, Bruno Dupuy, Neil F Fairweather, Dale N Gerding, Stuart Johnson, Ingo Just, David M Lyerly, Michel R Popoff, Julian I Rood, Abraham L Sonenshein, Monica Thelestam, Brendan W Wren, Tracy D Wilkins, and Christoph von Eichel-Streiber

  • Quorum sensing in Clostridium difficile: analysis of a luxS-type signalling system

    Glen P Carter, Des Purdy, Paul Williams, and Nigel P Minton

  • Effect of phage infection on toxin production by Clostridium difficile
    Shan Goh, Barbara J Chang, and Thomas V Riley

  • Generation of an erythromycin-sensitive derivative of Clostridium difficile strain 630 (630 erm) and demonstration that the conjugative transposon Tn916 E enters the genome of this strain at multiple sites

    Haitham A Hussain, Adam P Roberts, and Peter Mullany

  • Detection of binary-toxin genes (cdtA and cdtB) among Clostridium difficileC. difficile-associated diarrhoea (CDAD) in Poland

    strains isolated from patients with

    Hanna Pituch, Maja Rupnik, Piotr Obuch-Woszczatynski, Ana Grubesic, Felicja Meisel-Mikolajczyk, and Miroslaw Luczak

  • Prevalence and characteristics of bacteria and host factors in an outbreak situation of antibiotic-associated diarrhoea

    Grit Ackermann, Susanne Thomalla, Frank Ackermann, Reiner Schaumann, Arne C Rodloff, and Bernhard R Ruf

  • An improved protocol for pulsed-field gel electrophoresis typing of Clostridium difficile
    R Alonso, A Martín, T Peláez, M Marín, M Rodríguez-Creixéms, and E Bouza

  • Toxigenic status of Clostridium difficile in a large Spanish teaching hospital

    R Alonso, A Martín, T Peláez, M Marín, M Rodríguez-Creixéms, and E Bouza

  • PCR ribotyping of Clostridium difficile isolates originating from human and animal sources

    Luis G Arroyo, Stephen A Kruth, Barbara M Willey, Henry R Staempfli, Don E Low, and J Scott Weese

  • Typing by sequencing the slpA gene of Clostridium difficile strains causing multiple outbreaks in Japan

    Haru Kato, Toshiyuki Yokoyama, and Yoshichika Arakawa

  • Coexistence of multiple PCR-ribotype strains of Clostridium difficile in faecal samples limits epidemiological studies

    Renate J van den Berg, Hadi AA Ameen, Takahiro Furusawa, Eric CJ Claas, Eric R van der Vorm, and Ed J Kuijper

  • Clinical features of Clostridium difficile-associated diarrhoea due to binary toxin (actin-specific ADP-ribosyltransferase)-producing strains

    Frédéric Barbut, Dominique Decré, Valérie Lalande, Béatrice Burghoffer, Latifa Noussair, Anne Gigandon, Florence Espinasse, Laurent Raskine, Jérome Robert, Alain Mangeol, Catherine Branger, and Jean-Claude Petit

  • Laboratory diagnosis of Clostridium difficile-associated diarrhoea: a plea for culture

    Michel Delmée, Johan Van Broeck, Anne Simon, Michèle Janssens, and Véronique Avesani

  • Immunological properties of surface proteins of Clostridium difficile
    Séverine Péchiné, Aude Gleizes, Claire Janoir, Roseline Gorges-Kergot, Marie-Claude Barc, Michel Delmée, and Anne Collignon

  • Bovine antibody-enriched whey to aid in the prevention of a relapse of Clostridium difficile-associated diarrhoea: preclinical and preliminary clinical data

    Jaap T van Dissel, Nanda de Groot, Charles MH Hensgens, Sandra Numan, Ed J Kuijper, Peter Veldkamp, and Jan van 't Wout

Clostridium difficile ribotype 027, toxinotype III, the Netherlands.

25 September 2005

Ed Kuijper, R. van den Berg, S. Debast, C.E.Visser, D. Veenedaal, S. van den Hof and Daan Notermans
Summary: Outbreaks due to Clostridium difficile 027 have been detected in 7 hospitals in the Netherlands, involving more than 200 patients. Physicians report on a more severe couse of the disease and a lack of reponse to conventional therapy. The outbreaks are difficult to control. C. difficile 027 has also been isolated from patients with endemic forms of CDAD in two university hospitals.

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Revised nomenclature of Clostridium difficile toxins and associated genes.

At the recent First International C. difficile Symposium (FICDS, Kranjska Gora, Slovenia, May 2004), a round table discussion on C. difficile toxins and toxin gene nomenclature was held. Paper which summarizes the new nomenclature agreed to by the research groups currently active in the field, was published in J. Med. Microbiol., 2005, 54: 113-117.

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Outbreak in North America due to a new epidemic A+B+CDT+ strain

During the period from 2001 to 2004 increased rates and severity of C. difficile disease were observed in several US and Canadian hospitals (1, 2, 4, 5). Data from the US (see downloadable file below) indicate the presence of an epidemic strain that predominates in 6 of 7 studied hospitals (3) and preliminary studies have suggested that this strain may also be responsible for the Canadian outbreak (Canadian Press, October 13th, 2004).

The epidemic strain belongs to toxinotype III and REA type BI and has changes in the tcdA, tcdB and tcdC genes. It also produces an additional toxin, binary toxin CDT, so far found only in 2 to 20 % of clinical isolate surveys. Strains with the identical REA typing profile were documented in 1984. However, since then only 14 strains were included in the Chicago REA database maintained by Dr. Dale Gerding. Comparison of these historic isolates with new epidemic isolates has revealed development of fluoroquinolone resistance in the epidemic strain.

So far there is no report of similar outbreaks in Europe. Strains from toxinotype III were described in the two largest European collections from Cardiff (J. Brazier, strains ribotyped) and Brussels (M. Delmee, strains serotyped) (6, 7). Similar to the findings in the Chicago collection (D. Gerding, strains REA typed), toxinotype III strains were rare in the European collections.


  1. Dale Gerding and Stuart Johnson, personal communication.

  2. Eggertson L. C. difficile hits Sherbrooke, Que., hospital: 100 deaths. CMAJ. 2004 Aug 31;171(5):436.

  3. McDonald LC, Killgore GE, Thompson A, Johnson S, Gerding DN, and The Clostridium difficile Investigation Team. Emergence of an Epidemic Strain of Clostridium difficile in the United States, 2001-4: Potential Role for Virulence Factors and Antimicrobial Resistance Traits. Infectious Diseases Society of America 42th Annual Meeting. Boston, MA, September 30 - October 3, 2004. Abstract# LB-2. 

  4. Pepin J, Valiquette L, Alary ME, Villemure P, Pelletier A, Forget K, Pepin K, Chouinard D. Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity. CMAJ. 2004 Aug 31;171(5):466-72.

  5. Pindera L. Quebec to report on Clostridium difficile in 2005. CMAJ. 2004 Sep 28;171(7):715.

  6. Rupnik, M., Avesani, V., Janc, M., Eichel-Streiber, C.v. and Delmée M. (1998) A novel toxinotyping scheme and the correlation to serogrouping of Clostridium difficile isolates, J. Clin. Microbiol., 36: 2240-2247.

  7. Rupnik, M., Brazier, J. S., Duerden, B. I., Grabnar, M., and Stubbs, S. L. (2001) Comparison of toxinotyping and PCR ribotyping of Clostridium difficile

    strains and description of novel toxinotypes. Microbiology (UK), 147: 439-447.



A European survey of diagnostic methods and testing protocols for Clostridium difficile.

The Study Group has performed the survey "Diagnostic of C. difficile in Europe". The summary of results is available as presentation slides for download. This was published in CMI: Barbut F, Delmee M, Brazier JS et al. A European survey of diagnostic methods and testing protocols for Clostridium difficile. Clin Microbiol Infect 2003; 9: 989-996.

Summary of results

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Last update: 23 August 2016