Using genomics for the surveillance of antimicrobial resistance in Australia

Antimicrobial resistance (AMR) is a significant and growing global health threat. Efficient detection and identification of AMR transmission is critical to inform AMR surveillance and public health interventions. However, routine microbiological methods lack resolution to reliably identify transmission of AMR pathogens. Whole genome sequencing (WGS), or ‘genomics’, offers high-resolution identification of AMR mechanisms, pathogen typing and resolution of transmission networks. These data are increasingly being used at multiple levels, from the individual patient to hospitals to national surveillance. This thesis primarily describes the investigation of the use of genomics for AMR surveillance of bacterial pathogens relevant to human health, although these methods are also applicable to other pathogens and settings. Carbapenemase-producing Enterobacterales (CPE) are significant pathogens with resistance to carbapenems, considered last-line antimicrobials. Whilst small numbers of endemic CPE had been present in Australia since 2002, serious incursions with local transmission were not identified until 2012. In Chapter 2, a detailed analysis of CPE in the state of Victoria, Australia is presented, integrating genomic, phenotypic and epidemiologic data. Genomic analysis demonstrated a polyclonal population of CPE organisms, with three principal carbapenemase classes represented, and many different species represented. Study outcomes include facilitation of the state-wide CPE surveillance program by informing genomic analysis methods and baseline historical data, the establishment of phenotypic guidelines for suspected CPE, and designation of a genomic relatedness threshold for inferring CPE transmission. Genomic sequencing also has the potential to identify transmission of AMR pathogens in hospital settings, to inform infection control practices. Employing a ‘sequence first’ approach, prospectively sequencing all target AMR pathogens from hospital patients, represents a