Urinary tract infection (UTI) is a major cause of morbidity and mortality in persons with spinal cord injury (SCI). Frequent use of anti-microbial agents in patients with recurrent UTI creates selection pressure for te development of resistant bacteria. Therefore, there exists a pressing need to design and evaluate new approaches for prevention of UTI. The overall goal of this project is to develop a new approach for prevention of UTI in persons who rely in indwelling catheters for bladder drainage. The concept of using benign bacteria to prevent symptomatic infection, such as UTI, is known as bacterial interference. We previously demonstrated that intentional colonization of the bladders of patients with spinal cord injury with a non-pathogenic strain of Escherichia coli (83972) reduced the frequency of symptomatic UTI. We now propose to extend this principle of bacterial interference by inoculating urinary catheters with E. coli 83972 prior to insertion into patients' bladders. It is our hypothesis that colonization of bladder catheters with E. coli 83972 prior to insertion into patients may delay attachment of pathogenic bacteria to the catheter and thereby prevent UTI. Our preliminary studies show that this may be feasible. We found in vitro that incubation of urinary catheters with E. coli 83972 inhibited subsequent attachment by Enterococcus faecalis, a uropathogenic bacterium. In the current application we propose to examine the capacity of both wild-type and genetically enhanced E. coli 83972 to inhibit catheter adherence by various uropathogens and to clinically evaluate bladder catheters with pre-formed coating of E. coli 83972 in human subjects who experience recurrent UTI as a result of long-term catheterization. The results of the proposed studies may eventually benefit many types of people with mobility disorders who require indwelling bladder catheters for urinary drainage, including persons with SCI, children with spina bifida, stroke victims, and many nursing home residents. The research will be done in the Spinal Cord Injury Laboratory at the Houston Veterans' Affairs Medical Center and at Baylor College of Medicine. The candidate plans to combine her clinical background in infectious diseases with the mentored research preformed under this award in order to reduce the secondary infectious complications of mobility disorders.
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