AnTIC Follow-on Studies
Research type
Research Study
Full title
The role of genetics and antibiotic resistance in recurrent urinary tract infections: AnTIC follow-on studies
IRAS ID
243903
Contact name
Judith Hall
Contact email
Sponsor organisation
The Newcastle upon Tyne Hospitals NHS Foundation Trust
Duration of Study in the UK
1 years, 5 months, 31 days
Research summary
Research Summary
This project will analyse samples collected from participants in the AnTIC clinical trial which was completed in February 2017. The primary outcome of the AnTIC trial was to determine whether antibiotic prophylaxis results in a clinically significant reduction in the rate of symptomatic, antibiotic‐treated urinary tract infection suffered by people performing intermittent self-bladder catheterisation over 12 months and is cost‐effective for the UK NHS. The final report from the trial will be published by NIHR HTA in early August 2018.\nHere we propose two complimentary work packages to focus on the host (work package 1) and the bacterial profiles (work package 2) of the AnTIC trial.\nWORK PACKAGE 1: The aim of this first work package is to explore whether the recurrent urinary tract infections suffered by people using urinary catheters are linked to host genetic variations affecting proteins in the immune system which protect the urinary tract from infection by bacteria.\nWORK PACKAGE 2: The aim of this second work package is to answer the question: Does prophylactic treatment select for subtypes of uropathogenic bacterial species? To achieve our aim, we will genetically profile AnTIC bacterial isolates asking whether a trend is evident when correlating trial data and what antibiotic, if any, was used.\nOUTCOME: The data sample analyses from the two work packages, embodied into this project, will be linked to the clinical and demographic data collected from participants in the AnTIC trial.
Summary of Results
A recent clinical trial called AnTIC linked continuous low-dose antibiotic prophylaxis treatments to a lower incidence of symptomatic urinary tract infections (UTIs) in individuals performing clean intermittent self-catheterisation (CISC).
This study used blood and urine samples, and bugs (called Escherichia coli) isolated from these CISC patients to explore potential mechanisms underlying these protective effects. Analyses of the CISC patient DNAs showed that the number of infections suffered by the patients was not linked to a genetic defect in a specific receptor that detects urinary bugs. Analyses of patient urines for naturally produced agents that fight UTIs showed that the patient urinary responses, called innate immune responses, were robust and not significantly affected by taking antibiotics. Microbiological study data were limited to multi-drug resistant (MDR) Escherichia coli bugs isolated from patient urines. It was found that the urinary tracts of CISC participants prescribed low-dose prophylactic antibiotics were predominantly colonised by a single Escherichia coli bug, while participants given acute antibiotic treatments were colonised by several types of Escherichia coli bug. These findings suggested that for some CISC users, prophylaxis with low-dose antibiotics selected for a stable uromicrobiota that helped protect them from recurrent infections.REC name
North of Scotland Research Ethics Committee 1
REC reference
19/NS/0024
Date of REC Opinion
31 Jan 2019
REC opinion
Favourable Opinion