Novel Agents to Prevent Urinary Tract Infections

DESCRIPTION provided by applicant We combine the strengths of two researchers one at the University of Iowa and one at a biotechnology company Hennepin Life Sciences HLS to develop a pre exposure mucosal therapeutic PEMT to reduce the incidence of catheter associated urinary tract infections CAUTIs These infections may be acute and chronic Our plan is to develop a PEMT to reduce both types of infections Glycerol monolaurate GML as a non aqueous gel has been shown preliminarily to inhibit bacterial growth in vitro and in both bladders and on silicone tubes catheter material in vivo using a murine model of CAUTIs As noted in a HLS pre IND filing with FDA there are no safety concerns for use of a GML Gel in the human genitourinary tract in women GML Gel reduces vaginal pathogens that cause sexually transmitted infections bacterial vaginosis and candidiasis Our major hypothesis is that the dual acting anti infective GML Gel microbe and host targeted can be used as a PEMT to reduce the frequency and severity of bacterial growth in both bladders and on catheters in situ to prevent CAUTIs These are the most frequent health care associated infections and account for up to of hospital associated infections In addition of residents in long term care facilities have andgt day indwelling catheters In our planned studies we investigate the ability of GML to inhibit growth of Enterobacteriaceae Pseudomonas aeruginosa Staphylococcus aureus Enterococcus faecalis on foreign bodies in vitro and in the urinary tract in vivo Our studies are highly innovative as we seek to develop a low cost efficacious prophylaxis for CAUTIs The use of GML Gel provides an innovative approach for development of a microbicide since the gel inhibits bacterial infection and reduces the inflammatory environment Inflammation in CAUTIs can result in tissue damage in compromised individuals and the exposure of host molecules that act as receptors for bacterial adhesins No microbial resistance to either GML has been observed despite extensive studies this may result from the compound having numerous bacterial targets Two specific aims are proposed Specific Aim Evaluation of GML Gel killing of UTI pathogens and in preventing silicone catheter colonization in vitro Specific Aim Evaluation of GML Gel efficacy against bacterial pathogens in a murine model of CAUTI PUBLIC HEALTH RELEVANCE Gram negative and gram positive bacteria cause large numbers of catheter associated urinary tract infections with high cost This proposal examines the safety and ability of the generally recognized as safe GRAS compound glycerol monolaurate in a non aqueous gel to prevent these infections