Title: Defining Reservoirs of ESBL-Producing E. coli and the Threat Posed to Personal, Animal and Public Health in the UK
Funder: Department of Health (England)

Abstract: • Background – ESBL-producing E. coli cause c. 3000 cases of bacteraemia in the UK every year and perhaps 50-times that number of urinary tract infections. They are often resistant to multiple antibiotics, making effective treatment difficult in community or hospital settings and causing significant mortality. Resistant E. coli also occur in the environment and food animals, raising concerns of transmission via the food chain. However, the contribution of non-human reservoirs to the burden of human disease is uncertain. We will address this gap in knowledge using samples from five UK regions. • Aims – We will (i) determine the prevalence of gut carriage of ESBL-producing E. coli in humans; (ii) determine the optimum screening method for isolating ESBL producers from faeces; (iii) quantify ESBL producers in sewage, sampled from postcodes throughout the five UK regions; (iv) isolate ESBL producers from farm slurry and meat from retail outlets; (v) compare ESBL-producing E. coli from all sources to identify the most important reservoirs of strains that cause most human disease; and (vi) propose a national screening policy and identify strategic intervention points likely to enable reduction in the burden of ‘ESBL-associated disease’ in the UK. • Research plan and methods of investigation – Using samples collected specifically for the project, ESBL-producing E. coli will be detected using standardized protocols to allow direct comparison of regional data. The five regions are London, East Anglia and North-West England, plus Wales and Scotland. In each region we will seek ESBL producers (i) in faeces submitted to microbiology laboratories for diagnostic investigations, (ii) in sewage, sampled from postcodes throughout each region, (iii) in farm slurry and meat samples from retail outlets, and (iv) from bacteraemias. We will quantify the ESBL producers in each sample type and determine regional differences. The human faeces workpackage will include an evaluation (20,000-25,000 faeces samples) of three commercial culture media to determine which is most effective for isolating ESBL producers. We will characterize up to 1600 ESBL-producing E. coli (400 each from humans, slurry/meat and sewage, with equal numbers from each region, plus up to 400 bacteraemia isolates) using molecular methods (PCR, microarrays and whole-genome sequencing) to determine the proportions of major E. coli clones, the types of ESBL produced, the virulence potential of the strains and the genetic elements coding ESBLs. This will allow detailed analyses of relationships between the strains from animals and sewage and those found in humans, thereby informing transmission pathways. • Research team – a multidisciplinary team encompassing microbiologists and epidemiologists who enjoy national and international reputations. Expertise is drawn from human public health (HPA), animal health (AHVLA) and academia. Collectively the team have many years of experience working on antibiotic resistance issues, including ESBLs, have published extensively on the topic, and have established track records of securing grant income and successfully delivering large projects. • Potential impact/influence on the relevant policy field, users and wider stakeholders – We will provide the first nationally-relevant and structured analysis of ESBL-producing E. coli from human, slurry/meat and environmental (sewage) samples. The study is designed: (i) to inform strategic interventions (including national guidance on optimal screening for carriage of ESBL and associated interventions for carriers) and national policy on antimicrobial use and infection prevention and control aimed at reducing the burden of ESBL-associated disease and preventing further spread of multidrug resistant organisms; (ii) to determine the main reservoirs and routes of transmission; (iii) to determine interventions most likely to succeed in reducing the burden of ESBL-associated disease; and (iv) to inform recommendations on rapid molecular assays to identify disease-causing ESBL-strains.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT
Health categories: INFECTION