Defining reservoirs and transmission of antimicrobial resistant Escherichia coli using a One Health approach. (360G-Wellcome-110243_Z_15_Z)

Escherichia coli is a leading cause of infections in hospitals and the community. The increasing global prevalence of E. coli producing extended-spectrum beta-lactamases (ESBL-EC) represents a major public health challenge. ESBL-EC infections are associated with excess morbidity, mortality, longer hospital stay and higher healthcare costs. I aim to define the source(s) of ESBL-EC acquisition in a defined hospital population, in which I consider other patients, the hospital environment, food and water as potential sources. I will test the hypothesis that genome sequencing of ESBL-EC from these sources will define the major reservoirs for these strains and transmission pathways between them. I will place this genome data into a clinical context through a prospective longitudinal cohort study of ESBL-EC in hospitalised haematology patients. The most probable source(s) of new ESBL-EC acquisition in this cohort will be determined using epidemiological and whole genome sequence data on ESBL- EC from patients entering and leaving hospitals (n=975), the hospital environment (n=150), livestock (n=425), wastewater (n=425), a nearby nursing home (n=427), and bloodstream infections in the UK and Ireland (n=1519). Using mathematical modelling, I will infer transmission routes and predict the likely impact of different interventions on antimicrobial resistance reservoirs and transmission events