Prevalence and control of Clostridium difficile in patients with cystic fibrosis

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dc.contributor.advisor Hill, Colin en
dc.contributor.advisor Ross, R. Paul en Burke, Daniel G. 2016-09-08T11:09:07Z 2016-09-08T11:09:07Z 2014 2014
dc.identifier.citation Burke, D. G. 2014. Prevalence and control of Clostridium difficile in patients with cystic fibrosis. PhD Thesis, University College Cork. en
dc.identifier.endpage 219 en
dc.description.abstract The aim of this thesis was to investigate the high prevalence of Clostridium difficile in patients with cystic fibrosis (CF), and to control its dissemination. To determine the carriage rate of C. difficile in CF patients, 60 patients were tested for C. difficile and its toxin. In total, 50% of patients were found to be asymptomatic carriers of C. difficile despite toxin being detected in 31.66% of patients. Ribotyping of the C. difficile isolates revealed 16 distinct ribotypes, including the hyper virulent RT078. All isolates were sensitive to both Vancomycin and Metronidazole. The effect of CF and its treatment on the gut microbiota of CF patients was assessed by 16s sequencing of the gut microbiota of 68 CF patients. When compared to a healthy control group, CF patient gut microbiota was found to be less diverse and had an increased Firmicutes to Bacteriodetes ratio. Interestingly, CF patients who were carriers of C. difficile had a less diverse gut microbiota than C. difficile negative CF patients. Multilocus sequence typing was found to be comparable to PCR-ribotyping for typing C. difficile isolates from high risk patient groups. The sequence type ST 26 is potentially associated with CF patients as all seven isolates were found in this group and this sequence type has been previously reported in CF patients in a geographically distinct study. The bacteriophage ФCD6356 was assessed as a targeted antimicrobial against C. difficile in an ex-vivo model of the human distal colon. Despite reducing viable C. difficile by 1.75 logs over 24 hours, this bacteriophage was not suitable due to its lysogenic nature. Following treatment, all surviving C. difficile were immune to reinfection due to prophage integration. However, the ФCD6356 encoded endolysin was capable of reducing viable C. difficile by 2.9 over 2 hours in vitro after being cloned and expressed in Escherichia coli. en
dc.description.sponsorship Science Foundation Ireland (SFI-CSET grant 02/CE/B124) en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher University College Cork en
dc.rights © 2014, Daniel G. Burke. en
dc.rights.uri en
dc.subject Cystic fibrosis en
dc.subject Clostridium difficile en
dc.subject Microbiota en
dc.subject Bacteriophage en
dc.subject Epidemiology en
dc.subject Ribotyping en
dc.subject Multilocus sequence typing en
dc.title Prevalence and control of Clostridium difficile in patients with cystic fibrosis en
dc.type Doctoral thesis en
dc.type.qualificationlevel Doctoral en
dc.type.qualificationname PhD (Science) en
dc.internal.availability Full text available en No embargo required en
dc.description.version Accepted Version
dc.contributor.funder Science Foundation Ireland en
dc.description.status Not peer reviewed en Alimentary Pharmabotic Centre en Microbiology en Teagasc en
dc.check.type No Embargo Required
dc.check.reason No embargo required en
dc.check.opt-out Not applicable en
dc.thesis.opt-out false
dc.check.embargoformat Not applicable en
dc.internal.conferring Spring 2015 en

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© 2014, Daniel G. Burke. Except where otherwise noted, this item's license is described as © 2014, Daniel G. Burke.
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