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Title: Application of whole-genome sequencing to understand transmission of healthcare-associated Staphylococcus aureus
Author: Price, James Richard
Awarding Body: University of Brighton
Current Institution: University of Brighton
Date of Award: 2014
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Staphylococcus aureus is a leading cause of healthcare associated infection. Efforts to reduce the burden of S. aureus infections in healthcare settings have targeted patient carriage and preventing person-to-person transmission. These measures have only been partially successful. Our understanding of S. aureus transmission is limited by low discrimination of currently available typing techniques. The high resolution offered by whole-genome sequencing (WGS) has the potential to overcome these limitations. Work undertaken in this thesis exploits recent advances in WGS to understand S. aureus transmission in health care settings and in so doing establish the potential for WGS to replace current typing systems in infection control practice. The first study compares conventional approaches and WGS to investigate an outbreak of Methicillin Resistant S. aureus (M RSA) blood stream infections in a single UK hospital. By WGS, isolates within the EMRSA-16 lineage (one of the two dominant nosocomial MRSA lineages) showed strikingly low genetic diversity demonstrating the emergence of a clonal variant. This clonal variant, indistinguishable from the ancestral strain by conventional typing, accounted for 89% ofEMRSA-16 bacteraemia isolates at the outbreak hospital from 2006 and was associated with greater neutrophilia (p<0.00 1) compared with infection caused by other strains. Investigation of local and national S. aureus collections revealed the presence of isolates highly related to the variant in other hospitals across England, suggesting spread across large geographical areas. This represents the first report of a clonal variant being associated with an outbreak and provides novel insight into the epidemiology and population structures within dominant S. aureus lineages. The second study investigated the role of colonised patients as the source of new S. aureus acquisition in a hospital setting. Over 14 months all patients admitted to an adult intensive care unit were assessed for carriage, acquisition and their role in transmission. Among 680 patients where two or more serial samples were available only 44 acquisitions were observed. Isolates were available for genetic analysis from 37 acquisitions and among these only 7 (18.9%) could be explained by patient-topatient transmission. WGS disproved 3 transmission events indicated by conventional methods (spa-typing combined with overlapping patient stay) and also revealed 4 transmission and 2 acquisition events.
Supervisor: Not available Sponsor: In collaboration with UKCRC Modernising Medical Microbiology, Oxford
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: A000 Medicine