Genomic epidemiology and characterization of extended-spectrum beta-lactamase-producing Escherichia coli in Canadian hospitals from 2007 to 2016
| dc.contributor.author | Denisuik, Andrew James | |
| dc.contributor.examiningcommittee | Mulvey, Michael (Medical Microbiology and Infectious Diseases) | en_US |
| dc.contributor.examiningcommittee | Embree, Joanne (Medical Microbiology and Infectious Diseases) | en_US |
| dc.contributor.examiningcommittee | Zelenitsky, Sheryl (Pharmacy) | en_US |
| dc.contributor.examiningcommittee | Bush, Karen (Indiana University) | en_US |
| dc.contributor.supervisor | Zhanel, George (Medical Microbiology and Infectious Diseases) Adam, Heather (Medical Microbiology and Infectious Diseases) | en_US |
| dc.date.accessioned | 2022-01-18T18:54:25Z | |
| dc.date.available | 2022-01-18T18:54:25Z | |
| dc.date.copyright | 2022-01-11 | |
| dc.date.issued | 2022-01 | en_US |
| dc.date.submitted | 2022-01-11T21:03:02Z | en_US |
| dc.degree.discipline | Medical Microbiology and Infectious Diseases | en_US |
| dc.degree.level | Doctor of Philosophy (Ph.D.) | en_US |
| dc.description.abstract | Members of the Enterobacteriaceae, including Escherichia coli are among the top ranked bacterial pathogens in Canadian hospitals and -lactam antibiotics such as the oxyimino-cephalosporins are often used to treat such infections. Unfortunately, a growing proportion of E. coli strains demonstrate resistance to these essential agents, largely attributable to the production of extended- spectrum β-lactamases (ESBLs). Infections caused by ESBL-producing organisms pose a significant threat to patient outcomes, as these organisms undermine empiric regimens and often demonstrate concomitant resistant to multiple antimicrobial classes further limiting treatment options. The objective of this thesis was to determine the prevalence, antimicrobial susceptibilities, and genomic characteristics of these organisms circulating in Canadian hospitals. Clinical E. coli isolates were collected from January 2007 to December 2016 as part of the ongoing CANWARD national surveillance study. All isolates collected underwent antimicrobial susceptibility testing as well as phenotypic testing to identify ESBL-producing organisms. Molecular testing was subsequently used to confirm the presence of an ESBL genotype. All ESBL-producing strains underwent whole genome sequencing (WGS) to determine the distribution of sequence types, assess for the presence of various antimicrobial resistance genes, determine the phylogenetic relationship between strains, and to characterize ESBL-containing plasmid sequences. Statistically significant increases in the prevalence of ESBL-producing E. coli were observed during the study period. The prevalence of these organisms increased dramatically from a modest 3-5% between 2007 and 2010, to a maximum of over 12% in 2015. These increases were widespread, maintaining significance across multiple regions and demographic parameters. Multidrug resistance was common among ESBL-producing E. coli, as over 75% of strains were resistant to three or more antimicrobial classes. Within our cohort, sequence type (ST) 131 represented an overwhelming 62.5% of all isolates and representation of this clone increased alongside increasing prevalence of ESBL-producing organisms. While subclade C2/H30Rx represents the dominant sublineage identified, a growing proportion of subclade C1/H30 ST-131 isolates containing blaCTX-M-27 were identified and appear to be largely responsible for the increasing number of ESBL-producing isolates, particularly in the later years of CANWARD. While ST-131 represents the dominant clone, other lineages such as ST-648 and ST-1193 will require continued monitoring. | en_US |
| dc.description.note | February 2022 | en_US |
| dc.identifier.uri | http://hdl.handle.net/1993/36190 | |
| dc.language.iso | eng | en_US |
| dc.rights | open access | en_US |
| dc.subject | Antimicrobial resistance | en_US |
| dc.subject | Infectious diseases | en_US |
| dc.subject | Escherichia coli | en_US |
| dc.subject | Whole genome sequencing | en_US |
| dc.title | Genomic epidemiology and characterization of extended-spectrum beta-lactamase-producing Escherichia coli in Canadian hospitals from 2007 to 2016 | en_US |
| dc.type | doctoral thesis | en_US |
| local.subject.manitoba | yes | en_US |