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Genomic epidemiology of human Clostridioides (Clostridium) difficile infection in Australia, 2013-2018

O'Grady, Keeley (2021) Genomic epidemiology of human Clostridioides (Clostridium) difficile infection in Australia, 2013-2018. Other thesis, Murdoch University.

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Abstract

Clostridioides (Clostridium) difficile is an anaerobic pathogen found worldwide that is a leading cause of intestinal disease and prominent antimicrobial resistance (AMR) threat. Initially thought to be a hospital-acquired disease, it is increasingly being recognised in the community as well as in animal populations, with potential zoonotic transmission. Despite the high per-case burden C. difficile infection (CDI) places on healthcare systems and its potential as a reservoir of AMR genes for other pathogens, surveillance of resistance has been limited and inconsistent in Australia until recently.

In Australia’s first longitudinal and nationwide surveillance study for CDI, the C. difficile Antimicrobial Resistance Surveillance (CDARS) study, collected ~500 clinical isolates of C. difficile from 10 healthcare facilities around Australia between 2013-2018. Whole-genome sequencing was performed to enable high-resolution genomic and phylogenetic analysis and develop a comprehensive understanding of the genomic epidemiology, transmission, evolution and pathogenic potential of C. difficile in Australia.

This study found ~50% of samples contained three predominant PCR ribotypes (RTs): 014/020, 002 and 056. Core genome analysis determined that these RTs composed a genetically diverse group, with limited clonal relationships spread over large geographical areas, suggestive of widespread infection sources rather than transmission within the healthcare system. Binary toxin (CDT) genes were rare, with an A+B+CDT- toxin profile predominating. AMR was concentrated in multi-drug resistant RTs, with ~80% of all strains having no resistance determinants detected in silico. Resistance to macrolide lincosamide streptograminB (MLSB) and tetracycline class antimicrobials was most common, followed by aminoglycosides and fluoroquinolones, with rifamycin and other antimicrobial resistances rarely detected.

Overall, C. difficile in Australia appears divided into an antimicrobial susceptible, binary toxin negative majority and a minority of multidrug-resistant strains with increased pathogenic potential.

Item Type: Thesis (Other)
Murdoch Affiliation(s): Medical, Molecular and Forensic Sciences
Notes: Research Masters with Training
Supervisor(s): Riley, Thomas and Knight, Daniel
URI: http://researchrepository.murdoch.edu.au/id/eprint/65186
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