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 5% 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 5% GML Gel in the human genitourinary tract; in women 5% GML Gel reduces vaginal pathogens that cause sexually-transmitted infections, bacterial vaginosis, and candidiasis. Our major hypothesis is that the dual-acting anti-infective 5% 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 40% of hospital-associated infections. In addition, 5-10% of residents in long-term care facilities have >30 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 5% 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 1. Evaluation of 5% GML Gel killing of UTI pathogens and in preventing silicone catheter colonization in vitro. Specific Aim 2. Evaluation of 5% GML Gel efficacy against bacterial pathogens in a murine model of CAUTI.
Public Health Relevance Statement: 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.
Project Terms: Accounting; Acute; Adherence (attribute); Animal Model; Anti-Infective Agents; Antibiotic Resistance; Antibiotic-resistant organism; Antibiotics; antimicrobial; Bacteria; bacterial adhesin receptor; Bacterial Infections; Bacterial Vaginosis; base; Biological Factors; Biological Models; Biological Sciences; Biotechnology; Bladder; Candidiasis; catheter associated UTI; Catheterization; Catheters; Characteristics; Chronic; Cosmetics; cost; Cross Infection; Development; Disease; Dose; Enterobacteriaceae; Enterococcus faecalis; Environment; Epithelial Cells; Evaluation; Fatty Acids; Food; Foreign Bodies; Frequencies (time pattern); Gel; Genitourinary system; glycerol monolaurate; Gram-Positive Bacteria; Growth; Healthcare; Hospitals; Human; human disease; improved; In Situ; In Vitro; in vivo; Incidence; Individual; Indwelling Catheter; Infection; Infection prevention; Inflammation; Inflammatory; innovation; Iowa; Killings; Klebsiella pneumonia bacterium; Lactobacillus; Length; Long-Term Care; Microbe; microbial; Microbial Biofilms; microbicide; Modeling; Mus; NIH Program Announcements; nonhuman primate; novel; Organism; pathogen; prevent; Prophylactic treatment; Pseudomonas aeruginosa; public health relevance; quorum sensing; Recording of previous events; Research Personnel; Resistance; Role; Safety; Severities; Sexually Transmitted Diseases; Silicones; Small Business Innovation Research Grant; Staphylococcus aureus; technology development; Testing; Therapeutic; Tissues; Tube; Universities; urinary; Urinary tract; Urinary tract infection; Vagina; Woman
