Novel Agents to Prevent Urinary Tract Infections

预防尿路感染的新型药物

• 批准号: 8978407
• 负责人: Marnie L Peterson
• 金额: $ 18.73万
• 依托单位: HENNEPIN LIFE SCIENCES
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-06-25 至 2017-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8978407
• 关键词: Accounting; Acute; Adherence; Animal Model; Anti-Infective Agents; Antibiotic Resistance; Antibiotic-resistant organism; Antibiotics; Bacteria; Bacterial Infections; Bacterial Vaginosis; Biological Factors; Biological Models; Biological Sciences; Biotechnology; Bladder; Candidiasis; Catheterization; Catheters; Characteristics; Chronic; Cosmetics; Cross Infection; Development; Disease; Dose; Enterobacteriaceae; Enterococcus faecalis; Environment; Epithelial Cells; Evaluation; Fatty Acids; Food; Foreign Bodies; Frequencies; Gel; Genitourinary system; Gram-Positive Bacteria; Growth; Healthcare; Hospitals; Human; In Situ; In Vitro; Incidence; Individual; Indwelling Catheter; Infection; Infection prevention; Inflammation; Inflammatory; Iowa; Klebsiella pneumonia bacterium; Lactobacillus; Length; Long-Term Care; Microbe; Microbial Biofilms; Modeling; Mus; NIH Program Announcements; Organism; Prophylactic treatment; Pseudomonas aeruginosa; Recording of previous events; Research Personnel; Resistance; Role; Safety; Severities; Sexually Transmitted Diseases; Silicones; Small Business Innovation Research Grant; Staphylococcus aureus; Testing; Therapeutic; Tissues; Tube; Universities; Urinary tract; Urinary tract infection; Vagina; Woman; antimicrobial; bacterial adhesin receptor; base; catheter associated UTI; cost; glycerol monolaurate; human disease; improved; in vivo; innovation; killings; microbial; microbicide; nonhuman primate; novel; pathogen; prevent; public health relevance; quorum sensing; technology development; urinary

 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 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.

 描述（由适用提供）：我们结合了两名研究人员的优势，一名在爱荷华大学，一名生物技术公司Hennepin Life Sciences（HLS），以开发一种暴露前的粘膜治疗（PEMT），以减少导管仪相关尿液TRACTICTICT（CAUTIS）的发生率。这些感染可能是急性和慢性的。我们的计划是开发PEMT，以减少两种类型的感染。甘油单龙（GML）作为5％非水凝胶已被初步显示，以使用鼠类的鼠模型抑制体外，膀胱和硅胶管（导管材料）的体外和硅胶管（导管材料）的抑制。正如在HLS向FDA提交的申请中指出的那样，在人类泌尿生殖道中使用5％GML凝胶没有安全问题。在5％GML凝胶的女性中，可减少引起性传播感染，阴道细菌和念珠菌病的阴道病原体。我们的主要假设是，可以将双作用抗感染5％GML凝胶（微生物和宿主靶标）用作PEMT，以降低膀胱和原位导管中细菌生长的频率和严重程度，以防止丘特斯。这些是最常见的医疗保健相关感染，占医院相关感染的40％。此外，长期护理设施中有5-10％的居民具有> 30天的居住导管。在我们计划的研究中，我们研究了GML抑制肠杆菌科的生长，铜绿假单胞菌，金黄色葡萄球菌，粪肠球菌在体外和体内尿道上的能力。我们的研究具有高度创新性，因为我们试图为凯蒂（Cautis）开发低成本，高效的预防。 5％GML凝胶的使用为开发菌心的创新方法提供了一种创新的方法，因为凝胶会抑制细菌感染并降低炎症环境。肿瘤中的炎症会导致受损个体的组织损伤，并暴露于充当细菌依从性受体的宿主分子。尚未观察到对任何一种GML的微生物抗性，都没有观察到拼命的广泛研究。这可能是由于具有许多细菌靶标的化合物所致。提出了两个具体目的：具体目标1。评估5％GML凝胶杀死UTI病原体以及预防体外硅酮导管定植。具体目标2。在小鼠模型中，评估5％GML凝胶效率针对细菌病原体。