Epidemiology, diagnosis and treatment of bacterial infections

Principal investigator(s)

Prof. Dr. E.J. (Ed) Kuijper

C. difficile bacteriaDescription of the research

Clostridium difficile, a Gram positive, spore forming, anaerobic rod shaped bacterium, is the main cause of antibiotic-associated diarrhoea. Over 400 different PCR ribotypes (type) can be recognized, each with different microbiological  characteristics and specific clinical and epidemiological features. The department of Medical Microbiology serves as a National Reference Laboratory to coordinate and participate in a C. difficile infection (CDI) surveillance programme in the Netherlands and in Europe. Therefore, the laboratory intensively collaborates with the Centre for Infectious Disease Control at the National Institute for Public Health and the Environment (RIVM) and the European Centre for Disease Prevention and Control (ECDC). Because C. difficile responses less well to conventional treatment, novel therapeutic strategies are necessary. Immunological approaches are being investigated in our laboratory, mainly focussing on toxin-binding proteins and the role of the microbiome in CDI.

Research objectives

  • Develop new rapid diagnostic tests and typing techniques for CDI
  • Monitor the epidemiology of CDI in the Netherlands, and study the relatedness of CDI in humans and animals
  • Enhance the laboratory capacity for detection and surveillance of CDI in Europe, and build up and maintain a European C. difficile ribotyping nomenclature reference database
  • Develop new treatment strategies for CDI and its recurrences 

Key publications

  • An outbreak of Clostridium difficile infections due to new PCR ribotype 826: epidemiologic and microbiologic analyses. Crobach MJT, Voor In 't Holt AF, Knetsch CW, van Dorp SM, Bras W, Harmanus C, Kuijper EJ, Vos MC. Clin Microbiol Infect. 2017 Aug 19. pii: S1198-743X(17)30460-3. doi: 10.1016/j.cmi.2017.08.014.
  • Clinical and Microbiological Characteristics of Clostridium difficile Infection Among Hospitalized Children in the Netherlands. van Dorp SM, Smajlović E, Knetsch CW, Notermans DW, de Greeff SC, Kuijper EJ. Clin Infect Dis. 2017 Jan 15;64(2):192-198. doi: 10.1093/cid/ciw699. 
  • European Society of Clinical Microbiology and Infectious Diseases: update of the diagnostic guidance document for Clostridium difficile infection. Crobach MJ, Planche T, Eckert C, Barbut F, Terveer EM, Dekkers OM, Wilcox MH, Kuijper EJ. Clin Microbiol Infect. 2016 Aug;22 Suppl 4:S63-81. doi: 10.1016/j.cmi.2016.03.010. 
  • Survey of diagnostic and typing capacity for Clostridium difficile infection in Europe, 2011 and 2014. van Dorp SM, Notermans DW, Alblas J, Gastmeier P, Mentula S, Nagy E, Spigaglia P, Ivanova K, Fitzpatrick F, Barbut F, Morris T, Wilcox MH, Kinross P, Suetens C, Kuijper EJ; European Clostridium difficile Infection Surveillance Network (ECDIS-Net) project on behalf of all participants. Euro Surveill. 2016 Jul 21;21(29). doi: 10.2807/1560-7917.ES.2016.21.29.30292.
  • European Society of Clinical Microbiology and Infectious Diseases: update of the treatment guidance document for Clostridium difficile infection. Debast SB, Bauer MP, Kuijper EJ; European Society of Clinical Microbiology and Infectious Diseases. Clin Microbiol Infect. 2014; 20 Suppl 2:1-26
  • Whole genome sequencing reveals potential spread of Clostridium difficile between humans and farm animals in the Netherlands, 2002 to 2011. Knetsch CW, Connor TR, Mutreja A, van Dorp SM, Sanders IM, Browne HP, Harris D, Lipman L, Keessen EC, Corver J, Kuijper EJ, Lawley TD. Euro Surveill. 2014 Nov 13;19(45):20954.
  • Current application and future perspectives of molecular typing methods to study Clostridium difficile infections. Knetsch CW, Lawley TD, Hensgens MP, Corver J, Wilcox MW, Kuijper EJ. Euro Surveill. 2013 Jan 24;18(4):20381
  • Comparative analysis of an expanded Clostridium difficile reference strain collection reveals genetic diversity and evolution through six lineages. Knetsch CW, Terveer EM, Lauber C, Gorbalenya AE, Harmanus C, Kuijper EJ, Corver J, van Leeuwen HC. Infect Genet Evol. 2012 Oct;12(7):1577-85. doi: 10.1016/j.meegid.2012.06.003.
  • Clostridium difficile infection in Europe: a hospital-based survey. Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, Monnet DL, van Dissel JT, Kuijper EJ; for the ECDIS Study Group. Lancet. 2011; 377:63-73
  • Emergence of Clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Goorhuis A, Bakker D, Corver J, Debast SB, Harmanus C, Notermans DW, Bergwerff AA, Dekker FW, Kuijper EJ.  Clin Infect Dis. 2008; 47:1162-70

Research group

  • Celine Harmanus, BSc - Technician
  • Ed Kuijper, MD, PhD - Medical microbiologist
  • Ingrid Sanders, BSc - Technician
  • Monique Crobach, MD, PhD - Infectious disease specialist
  • Sofie van Dorp, MD - PhD student


  • Dr. O. Dekkers (Epidemiologist, LUMC, the Netherlands)
  • Prof. J. van Dissel (Professor of Infectious Diseases, LUMC, the Netherlands)
  • Dr. D. Notermans (Medical Microbiologist, RIVM, the Netherlands)
  • Dr. Sabine de Greeff (Epidemiologist, RIVM, the Netherlands)
  • Dr. Carl Suetens (Medical Epidemiologist, ECDC, Stockholm, Sweden)
  • Prof. M. Wilcox, (Microbiologist, Leeds University, UK)
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