Title: Risk Factors and Colonisation Rates of Multi-Resistant Gram Negative Bacteria Including Extended-Spectrum Beta-Lactamase and Carbapenemase Producing Coliforms (ESBL&Cpcs), in Different Sections of the Asymptomatic General Population and Validation of an Innovative Molecular Test to Detect ESBLs Using Bowel Cancer Faecal Occult Test (FOBt) Screening Cards
Funder: Department of Health (England)

Abstract: Background: Extensive use worldwide of third generation cephalosporins has led to the emergence of high levels of resistance caused by the production of Extended Spectrum Beta Lactamase (ESBL) and Carbapenemase-Producing Coliforms (CPC), herein abbreviated to ESBL&CPCs. Existing research has determined risk factors for infection in hospitalised patients which include older age, female gender, recurrent UTI’s, catheterisation, and antimicrobials.Rodriguez It is clear that pre-colonisation of the large bowel is an almost invariable precursor to infection, and that there are considerable reservoirs of community colonisation. It is thus essential to understand the distribution of colonisation in the general population and risk factors for community colonisation. The small number of previous colonisation studies in the UK have been based on opportunistic samples of clinical diarrhoeal specimens,Wickramasinghe or atypical populations such as nursing home residentsRooney, which are difficult to extrapolate to the general population. To address these research gaps we aim to investigate: 1) Absolute and relative differences in asymptomatic colonisation of ESBL&CPCs in and between different ethnic subgroups in a random sample of the general population in 3 regions of England. 2) Independent risk factors for colonisation in the general population. 3) The distribution of genotypes among those colonised with ESBL&CPCs and if these are influenced by the ethnic origin of individual and travel. 4) If FOBt cards are a valid tool for determining ESBL colonisation. Research plan and methods: We will estimate and compare the colonisation of ESBL&CPCs in stool samples in and between subgroups of 1560 patients selected from general practice lists in three areas of England which, based on their ethnic composition, are likely to have different levels of colonisation; (Birmingham with high ethnic diversity and known high colonisation, Shrewsbury with low ethnic diversity and Southampton with intermediate ethnic diversity). Patients randomly selected from practice lists stratified by age, ethnicity and antibiotic use, will be sent an invitation letter and then stool postal kit. A questionnaire will be used to collect data on potential risk factors for colonisation, including age, sex, travel, ethnicity, health care contact, antibiotic use, pets. We will detect ESBL&CPCs using traditional culture methodsXU and characterise using multiplex PCR, denaturing high-performance liquid chromatography and DNA sequencing.Poirel We will also validate an innovative PCR assay previously used to detect enterotoxigenic E. coli Grimes in FOBt cards, which has been piloted for ESBL detection in the Birmingham laboratory, on a subset of 140 ESBL culture positive and 140 culture negative samples. Sample size: Patients will continue to be randomly selected until we reach the sample size of 390 in each of four ethnic groups (Asian, Black, White British, Mixed British/Asian. Ethics: NRES are aware of our future application and have approved the molecular test and stool collection optimisation studies (NRES 11/SW/0235 and 11/SW/0236). This group is a strong collaboration of units with internationally recognised expertise in ESBL molecular work, primary care clinical work, epidemiology and research, bowel cancer screening and statistics. CMcNulty has led numerous studies in primary care, and has a reputation for completion. Impact: Increased understanding of the rates of asymptomatic faecal colonisation in different subgroups and associated risk factors will allow more targeted faecal screening and early identification of ESBL&CPC in patients identified as higher risk. Identifying colonised patients would allow targeted interventions in preadmission patients, and inform the development of interventions to reduce spread in the community when they are discharged. The FOBt card for ESBL diagnostics could simplify specimen collection in any future hospital preadmission screening, and could provide an opportunity to determine colonisation in individuals across England within the Bowel Cancer Screening Programme.


Research activity codes: 2.2 FACTORS RELATING TO PHYSICAL ENVIRONMENT;4.2 EVALUATION OF MARKERS AND TECHNOLOGIES
Health categories: INFECTION