Objectives: Clostridium difficile is a major global human pathogen divided into five clades, of which Glade 3 is the least characterized and consists predominantly of PCR ribotype (RT) 023 strains.... Show moreObjectives: Clostridium difficile is a major global human pathogen divided into five clades, of which Glade 3 is the least characterized and consists predominantly of PCR ribotype (RT) 023 strains. Our aim was to analyse and characterize this Glade.Methods: In this cohort study the clinical presentation of C. difficile RT023 infections was analysed in comparison with known 'hypervirulent' and non-hypervirulent strains, using data from the Netherlands national C. difficile surveillance programme. European RT023 strains of diverse origin were collected and whole-genome sequenced to determine the genetic similarity between isolates. Distinctive features were investigated and characterized.Results: Clinical presentation of C. difficile RT023 infections show severe infections akin to those seen with 'hypervirulent' strains from clades 2 (RT027) and 5 (RT078) (35%, 29% and 27% severe CDI, respectively), particularly with significantly more bloody diarrhoea than RT078 and non-hypervirulent strains (RT023 8%, other RTs 4%, p 0.036). The full genome sequence of strain CD305 is presented as a robust reference. Phylogenetic comparison of CD305 and a further 79 previously uncharacterized European RT023 strains of diverse origin revealed minor genetic divergence with >99.8% pairwise identity between strains. Analyses revealed distinctive features among Glade 3 strains, including conserved pathogenicity locus, binary toxin and phage insertion toxin genotypes, glycosylation of S-layer proteins, presence of the RT078 four-gene trehalose cluster and an esculinase-negative genotype.Conclusions: Given their recent emergence, virulence and genomic characteristics, the surveillance of Glade 3 strains should be more highly prioritized. (C) 2019 The Authors. Published by Elsevier Ltd on behalf of European Society of Clinical Microbiology and Infectious Diseases. Show less
Novakova, E.; Stefkovicova, M.; Kopilec, M.G.; Novak, M.; Kotlebova, N.; Kuijper, E.; Krutova, M. 2020
Aim: To obtain standardized epidemiological data for Clostridium difficile infection (CDI) in Slovakia.Methods: Between October and December 2016, 36 hospitals in Slovakia used the European Centre... Show moreAim: To obtain standardized epidemiological data for Clostridium difficile infection (CDI) in Slovakia.Methods: Between October and December 2016, 36 hospitals in Slovakia used the European Centre for Disease Prevention and Control (ECDC) Clostridium difficile infection (CDI) surveillance protocol.Results: The overall mean CDI incidence density was 2.8 (95% confidence interval 1.9-3.9) cases per 10 000 patient-days. Of 332 CDI cases, 273 (84.9%) were healthcare-associated, 45 (15.1%) were community-associated, and 14 (4.2%) were cases of recurrent CDI. A complicated course of CDI was reported in 14.8% of cases (n = 51). CDI outcome data were available for 95.5% of cases (n = 317). Of the 35 patients (11.1%) who died, 34 did so within 30 days after their CDI diagnosis.Of the 78 isolates obtained from 12 hospitals, 46 belonged to PCR ribotype 001 (59.0%; 11 hospitals) and 23 belonged to ribotype 176 (29.5%; six hospitals). A total of 73 isolates (93.6%) showed reduced susceptibility to moxifloxacin (ribotypes 001 and 176; p < 0.01). A reduced susceptibility to metronidazole was observed in 13 isolates that subsequently proved to be metronidazole-susceptible when, after thawing, they were retested using the agar dilution method. No reduced susceptibility to vancomycin was found.Conclusions: These results show the emergence of C. difficile ribotypes 027 and 176 with a predominance of ribotype 001 in Slovakia in 2016. Given that an almost homogeneous reduced susceptibility to moxifloxacin was detected in C. difficile isolates, this stresses the importance of reducing fluoroquinolone prescriptions in Slovak healthcare settings. (C) 2019 The Author(s). Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. Show less
Clostridium difficile infection (CDI) was discovered in 1978 as an important cause of antibiotic-associated diarrhoea. CDI became the most common healthcare-associated infection in Northern-America... Show moreClostridium difficile infection (CDI) was discovered in 1978 as an important cause of antibiotic-associated diarrhoea. CDI became the most common healthcare-associated infection in Northern-America and Europe during the antibiotic era, especially after global spread of a fluoroquinoloneresistant ribotype 027 strain in 2003. The rise of CDI urged the use of epidemiological surveillance systems to monitor disease dynamics and rapidly detect outbreaks. However, valid estimations of the infection burden of CDI in Europe were hampered by the heterogeneity and insufficiency of diagnostic algorithms for CDI, lack of standardised typing systems and incomplete surveillance methodologies. This thesis includes two studies conducted within a project named ‘the European CDI Surveillance Network’ focussing on enhancement of CDI surveillance and laboratory capacity for CDI in Europe. In the Netherlands, a sentinel surveillance system monitors the incidence of CDI in hospitals. This thesis describes (spatial) trends in the epidemiology of CDI in the Netherlands, in particular for children and the potentially zoonotic C. difficile ribotype 078. Data of a community-based case-control study was used to apply spatial scan statistics to detect CDI clustering beyond the hospital setting. Finally, this thesis provides directions for future epidemiological surveillance systems of CDI, both in the Netherlands and Europe. Show less
Since a decade, Clostridium difficile infection (CDI) has increased progressively in incidence and severity of disease. Currently, CDI is considered the leading cause of nosocomial diarrhoea,... Show moreSince a decade, Clostridium difficile infection (CDI) has increased progressively in incidence and severity of disease. Currently, CDI is considered the leading cause of nosocomial diarrhoea, associated with an increased duration of hospitalization, healthcare expenses, morbidity and mortality. This thesis describes our findings with outbreak control, diagnosis, identification of specific risk factors and treatment of CDI after the discovery of the emergence of C. difficile PCR-ribotype 027 in the Netherlands. The studies illustrate the role of antibiotics in relation to persistence, severeness and spreading of CDI. Antibiotics are shown to be a primary risk factor for the development of (ribotype-specific) CDI and an essential part of the outbreak control measures (__bundle-approach__), namely antibiotic stewardship. The use of antibacterials is a risk for selection of novel endemic C. difficile strains in e.g. animals, which introduce an increasing risk of alternative zoonotic transmission routes. Except for very mild CDI, which is clearly induced by usage of specific antibiotics, antibacterial treatment is advised. This thesis reviews the comparative effectiveness of the currently available treatment modalities, thereby providing evidence-based recommendations for CDI remedies. Treatment options include: oral and non-oral antibiotics, toxin-binding resins and polymers, immunotherapy, probiotics, faecal or bacterial intestinal transplantation. Show less
