Ribotypes and New Virulent Strains Across Europe

  • Jeanne Couturier
  • Kerrie Davies
  • Cécile Gateau
  • Frédéric Barbut
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1050)

Abstract

Clostridium difficile is a major bacterial cause of post-antibiotic diarrhoea. The epidemiology of C. difficile infections (CDI) has dramatically changed since the early 2000s, with an increasing incidence and severity across Europe. This trend is partly due to the emergence and rapid worldwide spread of the hypervirulent and epidemic PCR ribotype 027. Profiles of patients with CDI have also evolved, with description of community-acquired (CA) infections in patients with no traditional risk factors for CDI. However, recent epidemiological studies indicated that some European countries have successfully controlled the dissemination of the 027 clone whereas other countries recently reported the emergence of other virulent or unusual strains. The aims of this review are to summarize the current European CDI epidemiology and to describe the new virulent C. difficile strains circulating in Europe, as well as other potential emerging strains described elsewhere. Standardized typing methods and surveillance programmes are mandatory for a better understanding and monitoring of CDI in Europe.

Keywords

C. difficile PCR ribotypes Emerging strains European epidemiology Binary toxin 

References

  1. Alcalá L, Martin A, Marin M, Sánchez-Somolinos M, Catalán P, Peláez T, Bouza E (2012) The undiagnosed cases of Clostridium difficile infection in a whole nation: where is the problem? Clin Microbiol Infect 18:E204–E213.  https://doi.org/10.1111/j.1469-0691.2012.03883.x CrossRefGoogle Scholar
  2. Álvarez-Pérez S, Blanco JL, Harmanus C, Kuijper E, García ME (2017) Subtyping and antimicrobial susceptibility of Clostridium difficile PCR ribotype 078/126 isolates of human and animal origin. Vet Microbiol 199:15–22.  https://doi.org/10.1016/j.vetmic.2016.12.001 CrossRefGoogle Scholar
  3. Arvand M, Hauri AM, Zaiss NH, Witte W, Bettge-Weller G (2009) Clostridium difficile ribotypes 001, 017, and 027 are associated with lethal C. difficile infection in Hesse, Germany. Eurosurveillance 14(45):27–30Google Scholar
  4. Baines SD, O’Connor R, Freeman J, Fawley WN, Harmanus C, Mastrantonio P, Kuijper EJ, Wilcox MH (2008) Emergence of reduced susceptibility to metronidazole in Clostridium difficile. J Antimicrob Chemother 62:1046–1052.  https://doi.org/10.1093/jac/dkn313 CrossRefGoogle Scholar
  5. Baldan R, Trovato A, Bianchini V, Biancardi A, Cichero P, Mazzotti M, Nizzero P, Moro M, Ossi C, Scarpellini P, Cirillo DM (2015) Clostridium difficile PCR ribotype 018, a successful epidemic genotype. J Clin Microbiol 53:2575–2580.  https://doi.org/10.1128/JCM.00533-15 CrossRefPubMedCentralPubMedGoogle Scholar
  6. Barbanti F, Spigaglia P (2016) Characterization of Clostridium difficile PCR-ribotype 018: a problematic emerging type. Anaerobe 42:123–129.  https://doi.org/10.1016/j.anaerobe.2016.10.003 CrossRefGoogle Scholar
  7. Barbut F, Mastrantonio P, Delmee M, Brazier J, Kuijper E, Poxton I (2007) Prospective study of Clostridium difficile infections in Europe with phenotypic and genotypic characterisation of the isolates. Clin Microbiol Infect 13:1048–1057CrossRefPubMedGoogle Scholar
  8. Bartlett JG, Gerding DN (2008) Clinical recognition and diagnosis of Clostridium difficile infection. Clin Infect Dis 46:S12–S18.  https://doi.org/10.1086/521863 CrossRefGoogle Scholar
  9. Bauer MP, Notermans DW, van Benthem BH, Brazier JS, Wilcox MH, Rupnik M, Monnet DL, van Dissel JT, Kuijper EJ (2011) Clostridium difficile infection in Europe: a hospital-based survey. Lancet 377:63–73.  https://doi.org/10.1016/S0140-6736(10)61266-4 CrossRefPubMedCentralPubMedGoogle Scholar
  10. Bidet P, Barbut F, Lalande V, Burghoffer B, Petit J-C (1999) Development of a new PCR-ribotyping method for Clostridium difficile based on ribosomal RNA gene sequencing. FEMS Microbiol Lett 175:261–266.  https://doi.org/10.1111/j.1574-6968.1999.tb13629.x CrossRefGoogle Scholar
  11. Bidet P, Lalande V, Salauze B, Burghoffer B, Avesani V, Delmee M, Rossier A, Barbut F, Petit JC (2000) Comparison of PCR-ribotyping, arbitrarily primed PCR, and pulsed-field gel electrophoresis for typing Clostridium difficile. J Clin Microbiol 38:2484–2487PubMedCentralPubMedGoogle Scholar
  12. Birgand G, Blanckaert K, Carbonne A, Coignard B, Barbut F, Eckert C, Grandbastien B, Kadi Z, Astagneau P (2010) Investigation of a large outbreak of Clostridium difficile PCR-ribotype 027 infections in northern France, 2006–2007 and associated clusters in 2008–2009. Eurosurveillance 15(25):8–13Google Scholar
  13. Borgmann S, Kist M, Jakobiak T, Reil M, Scholz E, von Eichel-Streiber C, Gruber H, Brazier JS, Schulte B (2008) Increased number of Clostridium difficile infections and prevalence of Clostridium difficile PCR ribotype 001 in southern Germany. Eurosurveillance 13(49):11–15Google Scholar
  14. Bouza E, Alcalá L, Marín M, Valerio M, Reigadas E, Muñoz P, Vecchio MG-D, Egea V de (2017) An outbreak of Clostridium difficile PCR ribotype 027 in Spain: risk factors for recurrence and a novel treatment strategy. Eur J Clin Microbiol Infect Dis 36(10):1777–1786. doi:  https://doi.org/10.1007/s10096-017-2991-y CrossRefGoogle Scholar
  15. Cairns MD, Stabler RA, Shetty N, Wren BW (2012) The continually evolving Clostridium difficile species. Future Microbiol 7:945–957.  https://doi.org/10.2217/fmb.12.73 CrossRefGoogle Scholar
  16. Cairns MD, Preston MD, Lawley TD, Clark TG, Stabler RA, Wren BW (2015) Genomic epidemiology of a protracted hospital outbreak caused by a toxin A-negative Clostridium difficile sublineage PCR ribotype 017 strain in London, England. J Clin Microbiol 53:3141–3147.  https://doi.org/10.1128/JCM.00648-15 CrossRefPubMedCentralPubMedGoogle Scholar
  17. Cartman ST, Kelly ML, Heeg D, Heap JT, Minton NP (2012) Precise manipulation of the Clostridium difficile chromosome reveals a lack of association between the tcdC genotype and toxin production. Appl Environ Microbiol 78:4683–4690.  https://doi.org/10.1128/AEM.00249-12 CrossRefPubMedCentralPubMedGoogle Scholar
  18. Cassir N, Fahsi N, Durand G, Lagier J-C, Raoult D, Fournier P-E (2017) Emergence of Clostridium difficile tcdC variant 078 in Marseille, France. Eur J Clin Microbiol Infect Dis:1–4.  https://doi.org/10.1007/s10096-017-3022-8
  19. Chitnis AS, Holzbauer SM, Belflower RM, Winston LG, Bamberg WM, Lyons C, Farley MM, Dumyati GK, Wilson LE, Beldavs ZG, Dunn JR, Gould LH, MacCannell DR, Gerding DN, McDonald LC, Lessa FC (2013) Epidemiology of community-associated Clostridium difficile infection, 2009 through 2011. JAMA Intern Med 173:1359–1367.  https://doi.org/10.1001/jamainternmed.2013.7056 CrossRefGoogle Scholar
  20. Coignard B, Barbut F, Blanckaert K, Thiolet JM, Poujol I, Carbonne A, Petit JC, Desenclos JC (2006) Emergence of Clostridium difficile toxinotype III, PCR-ribotype 027-associated disease, France, 2006. Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull 11:E060914.1Google Scholar
  21. Collins DA, Hawkey PM, Riley TV (2013) Epidemiology of Clostridium difficile infection in Asia. Antimicrob Resist Infect Control 2:21.  https://doi.org/10.1186/2047-2994-2-21 CrossRefPubMedCentralPubMedGoogle Scholar
  22. Couturier J, Eckert C, Barbut F (2017) Spatio-temporal variability of the epidemic 027 Clostridium difficile strains in France based on MLVA typing. Anaerobe.  https://doi.org/10.1016/j.anaerobe.2017.08.007
  23. Davies KA, Longshaw CM, Davis GL, Bouza E, Barbut F, Barna Z, Delmée M, Fitzpatrick F, Ivanova K, Kuijper E, Macovei IS, Mentula S, Mastrantonio P, von Müller L, Oleastro M, Petinaki E, Pituch H, Norén T, Nováková E, Nyč O, Rupnik M, Schmid D, Wilcox MH (2014) Underdiagnosis of Clostridium difficile across Europe: the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID). Lancet Infect Dis 14:1208–1219.  https://doi.org/10.1016/S1473-3099(14)70991-0 CrossRefPubMedCentralPubMedGoogle Scholar
  24. Davies K, Davis G, Barbut F, Eckert C, Petrosillo N, Wilcox MH (2016a) Variability in testing policies and impact on reported Clostridium difficile infection rates: results from the pilot Longitudinal European Clostridium difficile Infection Diagnosis surveillance study (LuCID). Eur J Clin Microbiol Infect Dis 35:1949–1956.  https://doi.org/10.1007/s10096-016-2746-1 CrossRefPubMedCentralPubMedGoogle Scholar
  25. Davies KA, Ashwin H, Longshaw CM, Burns DA, Davis GL, Wilcox MH, on behalf of the EUCLID study group (2016b) Diversity of Clostridium difficile PCR ribotypes in Europe: results from the European, multicentre, prospective, biannual, point-prevalence study of Clostridium difficile infection in hospitalised patients with diarrhoea (EUCLID), 2012 and 2013. Euro Surveill 21(29)  https://doi.org/10.2807/1560-7917.ES.2016.21.29.30294
  26. De Almeida MN, Heffernan H, Dervan A, Bakker S, Freeman JT, Bhally H, Taylor SL, Riley TV, Roberts SA (2013) Severe Clostridium difficile infection in New Zealand associated with an emerging strain, PCR-ribotype 244. N Z Med J 126:9–14Google Scholar
  27. Debast SB, LAMG VL, Goorhuis A, Harmanus C, Kuijper EJ, Bergwerff AA (2009) Clostridium difficile PCR ribotype 078 toxinotype V found in diarrhoeal pigs identical to isolates from affected humans. Environ Microbiol 11:505–511.  https://doi.org/10.1111/j.1462-2920.2008.01790.x CrossRefGoogle Scholar
  28. Depitre C, Delmee M, Avesani V, Roels A, L’haridon R, Popoff M, Corthier G (1993) Serogroup F strains of Clostridium difficile produce toxin B but not toxin A. J Med Microbiol 38:434–441.  https://doi.org/10.1099/00222615-38-6-434 CrossRefGoogle Scholar
  29. Drabek J, Nyc O, Krutova M, Stovicek J, Matejkova J, Keil R (2015) Clinical features and characteristics of Clostridium difficile PCR-ribotype 176 infection: results from a 1-year university hospital internal ward study. Ann Clin Microbiol Antimicrob.  https://doi.org/10.1186/s12941-015-0114-0
  30. Drudy D, Harnedy N, Fanning S, Hannan M, Kyne L (2007) Emergence and control of fluoroquinolone-resistant, toxin A–negative, toxin B–positive Clostridium difficile. Infect Control Am Hosp Epidemiol 28:932–940.  https://doi.org/10.1086/519181 CrossRefGoogle Scholar
  31. Eckert C, Tessier C, Chassaing D, Barbut F (2011) Is deletion at 117 of the tcdC gene specific of PCR-ribotype 027 strains?Google Scholar
  32. Eckert C, Coignard B, Hebert M, Tarnaud C, Tessier C, Lemire A, Burghoffer B, Noel D, Barbut F (2013) Clinical and microbiological features of Clostridium difficile infections in France: the ICD-RAISIN 2009 national survey. Médecine Mal Infect 43:67–74.  https://doi.org/10.1016/j.medmal.2013.01.004 CrossRefGoogle Scholar
  33. Eckert C, Emirian A, Le Monnier A, Cathala L, De Montclos H, Goret J, Berger P, Petit A, De Chevigny A, Jean-Pierre H, Nebbad B, Camiade S, Meckenstock R, Lalande V, Marchandin H, Barbut F (2014) Prevalence and pathogenicity of binary toxin–positive Clostridium difficile strains that do not produce toxins A and B. New Microbes New Infect 3:12–17.  https://doi.org/10.1016/j.nmni.2014.10.003
  34. Eckert C, Bildan, M-A, Quach, S, Youssouf, A, Barbut, F, C. difficile study group (2015) Caractérisation des souches de Clostridium difficile circulant en France en 2014 et 2015: résultats d’une étude multicentrique (ref 350) – 35ème RICAIGoogle Scholar
  35. Eyre DW, Golubchik T, Gordon NC, Bowden R, Piazza P, Batty EM, CLC I, Wilson DJ, Didelot X, O’Connor L, Lay R, Buck D, Kearns AM, Shaw A, Paul J, Wilcox MH, Donnelly PJ, Peto TEA, Walker AS, Crook DW (2012) A pilot study of rapid benchtop sequencing of Staphylococcus aureus and Clostridium difficile for outbreak detection and surveillance. BMJ Open 2(3):e001124.  https://doi.org/10.1136/bmjopen-2012-001124 CrossRefPubMedGoogle Scholar
  36. Eyre DW, Tracey L, Elliott B, Slimings C, Huntington PG, Stuart RL, Korman TM, Kotsiou G, McCann R, Griffiths D, Fawley WN, Armstrong P, Dingle KE, Walker AS, Peto TE, Crook DW, Wilcox MH, Riley TV (2015) Emergence and spread of predominantly community-onset Clostridium difficile PCR ribotype 244 infection in Australia, 2010 to 2012. Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull 20:21059Google Scholar
  37. Fawley WN, Knetsch CW, MacCannell DR, Harmanus C, Du T, Mulvey MR, Paulick A, Anderson L, Kuijper EJ, Wilcox MH (2015) Development and validation of an internationally-standardized, high-resolution capillary gel-based electrophoresis PCR-ribotyping protocol for Clostridium difficile. PLoS One.  https://doi.org/10.1371/journal.pone.0118150
  38. Fawley WN, Davies KA, Morris T, Parnell P, Howe R, Wilcox MH, Clostridium difficile Ribotyping Network (CDRN) Working Group (2016) Enhanced surveillance of Clostridium difficile infection occurring outside hospital, England, 2011 to 2013. Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull.  https://doi.org/10.2807/1560-7917.ES.2016.21.29.30295
  39. Geric B, Carman RJ, Rupnik M, Genheimer CW, Sambol SP, Lyerly DM, Gerding DN, Johnson S (2006) Binary toxin–producing, large clostridial toxin–negative Clostridium difficile strains are enterotoxic but do not cause disease in hamsters. J Infect Dis 193:1143–1150.  https://doi.org/10.1086/501368 CrossRefPubMedGoogle Scholar
  40. Goorhuis A, Bakker D, Corver J, Debast SB, Harmanus C, Notermans DW, Bergwerff AA, Dekker FW, Kuijper EJ (2008) Emergence of Clostridium difficile infection due to a new hypervirulent strain, polymerase chain reaction ribotype 078. Clin Infect Dis Off Publ Infect Dis Soc Am 47:1162–1170.  https://doi.org/10.1086/592257 CrossRefGoogle Scholar
  41. Gupta A, Khanna S (2014) Community-acquired Clostridium difficile infection: an increasing public health threat. Infect Drug Resist 7:63–72.  https://doi.org/10.2147/IDR.S46780 CrossRefPubMedCentralPubMedGoogle Scholar
  42. Hensgens MP, Goorhuis A, Notermans DW, van Benthem BH, Kuijper EJ (2009) Decrease of hypervirulent Clostridium difficile PCR ribotype 027 in the Netherlands. Eurosurveillance 14(45):7–9Google Scholar
  43. Indra A, Huhulescu S, Schneeweis M, Hasenberger P, Kernbichler S, Fiedler A, Wewalka G, Allerberger F, Kuijper EJ (2008) Characterization of Clostridium difficile isolates using capillary gel electrophoresis-based PCR ribotyping. J Med Microbiol 57:1377–1382.  https://doi.org/10.1099/jmm.0.47714-0 CrossRefPubMedCentralPubMedGoogle Scholar
  44. Janezic S, Strumbelj I, Rupnik M (2011) Use of modified PCR ribotyping for direct detection of Clostridium difficile ribotypes in stool samples. J Clin Microbiol 49:3024–3025.  https://doi.org/10.1128/JCM.01013-11 CrossRefPubMedCentralPubMedGoogle Scholar
  45. Kato H, Kato N, Watanabe K, Iwai N, Nakamura H, Yamamoto T, Suzuki K, Kim S-M, Chong Y, Wasito EB (1998) Identification of toxin A-negative, toxin B-positive Clostridium difficile by PCR. J Clin Microbiol 36:2178–2182PubMedCentralPubMedGoogle Scholar
  46. Killgore G, Thompson A, Johnson S, Brazier J, Kuijper E, Pepin J, Frost EH, Savelkoul P, Nicholson B, van den Berg RJ, Kato H, Sambol SP, Zukowski W, Woods C, Limbago B, Gerding DN, McDonald LC (2008) Comparison of seven techniques for typing international epidemic strains of Clostridium difficile: restriction endonuclease analysis, pulsed-field gel electrophoresis, PCR-ribotyping, multilocus sequence typing, multilocus variable-number tandem-repeat analysis, amplified fragment length polymorphism, and surface layer protein A gene sequence typing. J Clin Microbiol 46:431–437.  https://doi.org/10.1128/JCM.01484-07 CrossRefGoogle Scholar
  47. Knetsch EC for DP and C (ECDC)-HCU-E editorial (2013) Current application and future perspectives of molecular typing methods to study Clostridium difficile infections. http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20381. Accessed 2 Dec 2014
  48. Knetsch CW, Hensgens MPM, Harmanus C, van der Bijl MW, Savelkoul PHM, Kuijper EJ, Corver J, van Leeuwen HC (2011) Genetic markers for Clostridium difficile lineages linked to hypervirulence. Microbiology 157:3113–3123.  https://doi.org/10.1099/mic.0.051953-0 CrossRefGoogle Scholar
  49. Kristjánsson M, Samore MH, Gerding DN, De Girolami PC, Bettin KM, Karchmer AW, Arbeit RD (1994) Comparison of restriction endonuclease analysis, ribotyping, and pulsed-field gel electrophoresis for molecular differentiation of Clostridium difficile strains. J Clin Microbiol 32:1963–1969PubMedCentralPubMedGoogle Scholar
  50. Krutova M, Matejkova J, Tkadlec J, Nyc O (2015) Antibiotic profiling of Clostridium difficile ribotype 176 – a multidrug resistant relative to C. difficile ribotype 027. Anaerobe 36:88–90.  https://doi.org/10.1016/j.anaerobe.2015.07.009 CrossRefGoogle Scholar
  51. Krutova M, Matejkova J, Kuijper EJ, Drevinek P, Nyc O, Czech Clostridium difficile study group (2016) Clostridium difficile PCR ribotypes 001 and 176 – the common denominator of C. difficile infection epidemiology in the Czech Republic, 2014. Euro Surveill.  https://doi.org/10.2807/1560-7917.ES.2016.21.29.30296
  52. Kuijper E, Weerdt J, Kato H, Kato N, Dam A, Vorm E, Weel J, Rheenen C, Dankert J (2001) Nosocomial outbreak of Clostridium difficile-associated diarrhoea due to a clindamycin-resistant enterotoxin A-negative strain. Eur J Clin Microbiol Infect Dis 20:528–534.  https://doi.org/10.1007/s100960100550 CrossRefGoogle Scholar
  53. Lessa FC, Mu Y, Bamberg WM, Beldavs ZG, Dumyati GK, Dunn JR, Farley MM, Holzbauer SM, Meek JI, Phipps EC, Wilson LE, Winston LG, Cohen JA, Limbago BM, Fridkin SK, Gerding DN, McDonald LC (2015) Burden of Clostridium difficile infection in the United States. N Engl J Med 372:825–834.  https://doi.org/10.1056/NEJMoa1408913 CrossRefGoogle Scholar
  54. Lim SK, Stuart RL, Mackin KE, Carter GP, Kotsanas D, Francis MJ, Easton M, Dimovski K, Elliott B, Riley TV, Hogg G, Paul E, Korman TM, Seemann T, Stinear TP, Lyras D, Jenkin GA (2014) Emergence of a ribotype 244 strain of Clostridium difficile associated with severe disease and related to the epidemic ribotype 027 strain. Clin Infect Dis 58:1723–1730.  https://doi.org/10.1093/cid/ciu203 CrossRefGoogle Scholar
  55. Marsh JW, O’Leary MM, Shutt KA, Pasculle AW, Johnson S, Gerding DN, Muto CA, Harrison LH (2006) Multilocus variable-number tandem-repeat analysis for investigation of Clostridium difficile transmission in hospitals. J Clin Microbiol 44:2558–2566.  https://doi.org/10.1128/JCM.02364-05 CrossRefPubMedCentralPubMedGoogle Scholar
  56. Metcalf DS, Costa MC, Dew WMV, Weese JS (2010) Clostridium difficile in vegetables, Canada. Lett Appl Microbiol 51:600–602.  https://doi.org/10.1111/j.1472-765X.2010.02933.x CrossRefGoogle Scholar
  57. Monot M, Eckert C, Lemire A, Hamiot A, Dubois T, Tessier C, Dumoulard B, Hamel B, Petit A, Lalande V, Ma L, Bouchier C, Barbut F, Dupuy B (2015) Clostridium difficile: new insights into the evolution of the pathogenicity locus. Sci Rep.  https://doi.org/10.1038/srep15023
  58. Murray R, Boyd D, Levett PN, Mulvey MR, Alfa MJ (2009) Truncation in the tcdC region of the Clostridium difficile pathLoc of clinical isolates does not predict increased biological activity of toxin B or toxin A. BMC Infect Dis 9:103.  https://doi.org/10.1186/1471-2334-9-103 CrossRefPubMedCentralPubMedGoogle Scholar
  59. Neely F, Lambert M-L, Van Broeck J, Delmée M (2017) Clinical and laboratory features of the most common Clostridium difficile ribotypes isolated in Belgium. J Hosp Infect 95:394–399.  https://doi.org/10.1016/j.jhin.2016.12.011 CrossRefGoogle Scholar
  60. Nyč O, Pituch H, Matějková J, Obuch-Woszczatynski P, Kuijper EJ (2011) Clostridium difficile PCR ribotype 176 in the Czech Republic and Poland. Lancet 377:1407.  https://doi.org/10.1016/S0140-6736(11)60575-8 CrossRefGoogle Scholar
  61. Obuch-Woszczatyński P, Lachowicz D, Schneider A, Mól A, Pawłowska J, Ożdżeńska-Milke E, Pruszczyk P, Wultańska D, Młynarczyk G, Harmanus C, Kuijper EJ, van Belkum A, Pituch H (2014) Occurrence of Clostridium difficile PCR-ribotype 027 and it’s closely related PCR-ribotype 176 in hospitals in Poland in 2008–2010. Anaerobe 28:13–17.  https://doi.org/10.1016/j.anaerobe.2014.04.007 CrossRefGoogle Scholar
  62. Pituch H, van den Braak N, van Leeuwen W, van Belkum A, Martirosian G, Obuch-Woszczatyński P, Łuczak M, Meisel-Mikołajczyk F (2001) Clonal dissemination of a toxin-A-negative/toxin-B-positive Clostridium difficile strain from patients with antibiotic-associated diarrhea in Poland. Clin Microbiol Infect 7:442–446.  https://doi.org/10.1046/j.1198-743x.2001.00312.x CrossRefGoogle Scholar
  63. Pruitt RN, Lacy DB (2012) Toward a structural understanding of Clostridium difficile toxins A and B. Front Cell Infect Microbiol 2:28.  https://doi.org/10.3389/fcimb.2012.00028
  64. Romano V, Pasquale V, Krovacek K, Mauri F, Demarta A, Dumontet S (2012) Toxigenic Clostridium difficile PCR ribotypes from wastewater treatment plants in Southern Switzerland. Appl Environ Microbiol 78:6643–6646.  https://doi.org/10.1128/AEM.01379-12 CrossRefPubMedCentralPubMedGoogle Scholar
  65. Rupnik M, Janezic S (2016) An update on Clostridium difficile toxinotyping. J Clin Microbiol 54:13–18.  https://doi.org/10.1128/JCM.02083-15 CrossRefGoogle Scholar
  66. Rupnik M, Avesani V, Janc M, von Eichel-Streiber C, Delmée M (1998) A novel toxinotyping scheme and correlation of toxinotypes with serogroups of Clostridium difficile isolates. J Clin Microbiol 36:2240–2247PubMedCentralPubMedGoogle Scholar
  67. Rupnik M, Brazier JS, Duerden BI, Grabnar M, Stubbs SL (2001) Comparison of toxinotyping and PCR ribotyping of Clostridium difficile strains and description of novel toxinotypes. Microbiol Read Engl 147:439–447.  https://doi.org/10.1099/00221287-147-2-439 CrossRefGoogle Scholar
  68. Rupnik M, Tambic Andrasevic A, Trajkovska Dokic E, Matas I, Jovanovic M, Pasic S, Kocuvan A, Janezic S (2016) Distribution of Clostridium difficile PCR ribotypes and high proportion of 027 and 176 in some hospitals in four South Eastern European countries. Anaerobe 42:142–144.  https://doi.org/10.1016/j.anaerobe.2016.10.005 CrossRefGoogle Scholar
  69. Santos A, Isidro J, Silva C, Boaventura L, Diogo J, Faustino A, Toscano C, Oleastro M (2016) Molecular and epidemiologic study of Clostridium difficile reveals unusual heterogeneity in clinical strains circulating in different regions in Portugal. Clin Microbiol Infect 22:695–700.  https://doi.org/10.1016/j.cmi.2016.04.002 CrossRefGoogle Scholar
  70. Schneeberg A, Neubauer H, Schmoock G, Baier S, Harlizius J, Nienhoff H, Brase K, Zimmermann S, Seyboldt C (2013) Clostridium difficile genotypes in piglet populations in Germany. J Clin Microbiol 51:3796–3803.  https://doi.org/10.1128/JCM.01440-13 CrossRefPubMedCentralPubMedGoogle Scholar
  71. Smith A (2005) Outbreak of Clostridium difficile infection in an English hospital linked to hypertoxin-producing strains in Canada and the US. Euro Surveill Bull Eur Sur Mal Transm Eur Commun Dis Bull 10:E050630.2Google Scholar
  72. Spigaglia P, Barbanti F, Dionisi AM, Mastrantonio P (2010) Clostridium difficile isolates resistant to fluoroquinolones in Italy: emergence of PCR ribotype 018. J Clin Microbiol 48:2892–2896.  https://doi.org/10.1128/JCM.02482-09 CrossRefPubMedCentralPubMedGoogle Scholar
  73. Stabler RA, Gerding DN, Songer JG, Drudy D, Brazier JS, Trinh HT, Witney AA, Hinds J, Wren BW (2006) Comparative phylogenomics of Clostridium difficile reveals clade specificity and microevolution of hypervirulent strains. J Bacteriol 188:7297–7305.  https://doi.org/10.1128/JB.00664-06 CrossRefPubMedCentralPubMedGoogle Scholar
  74. Stubbs SL, Brazier JS, O’Neill GL, Duerden BI (1999) PCR targeted to the 16S-23S rRNA gene intergenic spacer region of Clostridium difficile and construction of a library consisting of 116 different PCR ribotypes. J Clin Microbiol 37:461–463PubMedCentralPubMedGoogle Scholar
  75. Sundram F, Guyot A, Carboo I, Green S, Lilaonitkul M, Scourfield A (2009) Clostridium difficile ribotypes 027 and 106: clinical outcomes and risk factors. J Hosp Infect 72:111–118.  https://doi.org/10.1016/j.jhin.2009.02.020 CrossRefGoogle Scholar
  76. Taori SK, Wroe A, Hardie A, Gibb AP, Poxton IR (2014) A prospective study of community-associated Clostridium difficile infections: the role of antibiotics and co-infections. J Infect 69:134–144.  https://doi.org/10.1016/j.jinf.2014.04.002 CrossRefGoogle Scholar
  77. Valiente E, Dawson LF, Cairns MD, Stabler RA, Wren BW (2012) Emergence of new PCR ribotypes from the hypervirulent Clostridium difficile 027 lineage. J Med Microbiol 61:49–56.  https://doi.org/10.1099/jmm.0.036194-0 CrossRefGoogle Scholar
  78. von Müller L, Mock M, Halfmann A, Stahlmann J, Simon A, Herrmann M (2015) Epidemiology of Clostridium difficile in Germany based on a single center long-term surveillance and German-wide genotyping of recent isolates provided to the advisory laboratory for diagnostic reasons. Int J Med Microbiol 305:807–813.  https://doi.org/10.1016/j.ijmm.2015.08.035 CrossRefGoogle Scholar
  79. Warny M, Pepin J, Fang A, Killgore G, Thompson A, Brazier J, Frost E, McDonald LC (2005) Toxin production by an emerging strain of Clostridium difficile associated with outbreaks of severe disease in North America and Europe. Lancet 366:1079–1084.  https://doi.org/10.1016/S0140-6736(05)67420-X CrossRefPubMedCentralPubMedGoogle Scholar
  80. Wilcox MH, Mooney L, Bendall R, Settle CD, Fawley WN (2008) A case-control study of community-associated Clostridium difficile infection. J Antimicrob Chemother 62:388–396.  https://doi.org/10.1093/jac/dkn163 CrossRefPubMedCentralPubMedGoogle Scholar

Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Jeanne Couturier
    • 1
    • 2
  • Kerrie Davies
    • 3
  • Cécile Gateau
    • 1
  • Frédéric Barbut
    • 1
    • 2
  1. 1.National Reference Laboratory for C. difficile, Hôpital Saint-AntoineParisFrance
  2. 2.Université Paris Descartes, Faculté de PharmacieParisFrance
  3. 3.Healthcare Associated Infections Research GroupLeeds Teaching Hospitals NHS Trust and University of LeedsLeedsUK

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