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Hospital acquired infections (HAIs) are a major threat to patient safety, and in locations with poor surveillance and infection control such infections can be associated with high mortality rates. The problem of hospital transmission of hazardous bacteria is further exacerbated by the emergence of antimicrobial resistance, particularly extended spectrum ? lactamases (ESBLs) and carbapenemases in Gram-negative bacteria. Clinical management of HAIs is adversely affected by a lack of detailed evidence on the routes of transmission and how to prevent them. Healthcare settings across Asia are under increasing pressure to control and prevent multidrug-resistant (MDR) HAIs. Recent work (collaboration between Baker and Thomson) has specifically highlighted nosocomial bloodstream infections (BSIs) as a major cause of mortality in high dependency units. Notably, in 2012 two outbreaks of Klebsiella pneumoniae occurred in the neonatal intensive care unit (NICU) in a tertiary hospital in Nepal, which had a mortality rate of 75%. This study found that there are regular peaks in BSIs across the hospital; these trends are being echoed in other healthcare setting across Asia. These peaks in outbreaks are driven by an increase in the rate isolation (from blood) of E. coli and K. pneumoniae that are resistant to most available antimicrobials. Understanding the epidemiology of these infections across Asia is required to enhance infection control measures, to optimize therapeutic approaches, to minimize further emergence of antimicrobial resistance and to prevent morbidity and mortality. This project centres around the genetic epidemiology of E. coli and K. pneumoniae causing BSIs in hospitals in Asia. Specifically, Oxford MPhil student, Tu Le Thi Phuong, will compare the genomic structures between E. coli and K.pneumoniae associated with BSIs in comparison to infections in other sites. The hypothesis, built on our preliminary data, is that specific genetic loci including antimicrobial resistance genes and siderophores are related to a more invasive phenotype (in comparison to non-invasive phenotypes, including UTIs and respiratory infections). To test this hypothesis Tu will access collections of E. coli and K. pneumoniae isolates cultured from blood and other sites (e.g. urine, skin, tracheal aspirates) from hospitals across Asia and part of the Wellcome Trust major overseas programme. She will aim to collect 500 bacteria from stool (as a comparator and BSI in these locations and determine their phylogenetic relationship to each other and their non-core genome content. Genomic data will be stratified by location (country of isolation) and site of culture (blood/non-blood) and Tu will identify genes associated with specific disease phenotypes. This data is part of a pre-publication release. For information on the proper use of pre-publication data shared by the Wellcome Trust Sanger Institute (including details of any publication moratoria), please see http://www.sanger.ac.uk/datasharing/ |