This proposal addresses the chronic and costly problem of catheter-associated urinary tract infection (CAUTI) in individuals with long-term urinary catheters. Such persons are chronically bacteriuric and suffer recurrent morbidities from tissue invasion by uropathogens. Our preventive approach to CAUTI uses bacterial interference, as we deliberately inoculate catheterized persons' bladders with benign flora in order to prevent symptomatic infection by pathogens. This novel probiotic-based approach avoids use of antimicrobial agents and thus does not select for resistance in the human host's flora. The overall goal of this proposal is to conduct a pilot trial of urinary catheters coated with a benign strain of E. coli (HU2117) as a means to inoculate the bladders of older persons with long-term urinary catheters. E. coli HU2117 is a derivative of wild-type asymptomatic bacteriuria strain E. coli 83972 in which the gene for P pili has been deleted, preventing expression of this possible virulence factor. We have previously used E. coli HU2117 to deliberately inoculate the bladders of 114 human subjects with neurogenic bladders secondary to spinal cord injury. The current proposal has two specific aims: (1) to test the hypothesis that urinary catheters coated with a biofilm of benign E. coli HU2117 will be a safe and effective means to colonize the bladders of older persons wearing long-term indwelling urinary catheters, and (2) to test the hypothesis that microbiological changes in the bladder and catheter flora before and after insertion of catheters coated with E. coli HU2117 will predict success or failure of bladder colonization and prevention of superinfection. The research design is a prospective clinical trial in which all 20 subjects wil receive a study catheter that has been pre-coated with E. coli HU2117. Subjects will be > 50 years of age, dependent upon long-term catheters for bladder drainage, and will have baseline bacteriuria. The study catheters will be left in the bladder for 28 days and then will be removed for microbiological analysis. Subjects will be followed with serial urine cultures until disappearance of E. coli HU2117 from their urine and for serious adverse events over 12 months. Our primary outcomes for Aim 1 are safety, rates of CAUTI, colonization success. Safety is defined as no subject experiencing symptomatic CAUTI or a serious adverse event definitely related to E. coli HU2117. The rates of symptomatic CAUTI will be recorded before, during, and after colonization with E. coli HU2117. Colonization success is defined as the presence of E. coli HU2117 in the urine at 28 days after study catheter insertion. For Aim 2, data will be collected through serial, quantitative urine cultures from subjects before, during, an after colonization as well as from culture and microscopy studies of the removed study catheters. The goal of Aim 2 is to develop prediction rules for colonization success and prevention of superinfection. If this pilot trial is successful, the results will be used to designa randomized, placebo-controlled trial of these E. coli-coated catheters as a means to prevent CAUTI. The trial protocol has been approved by the FDA (IND #14007).

R21DK092293

2012-05-15

2015-04-30