Bacterial Interference to Prevent Catheter-Associated Urinary Tract Infection

预防导管相关性尿路感染的细菌干扰

• 批准号: 8301867
• 负责人: BARBARA Wells TRAUTNER
• 金额: $ 19.56万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-05-15 至 2014-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8301867
• 关键词: Address; Age; Antibiotic susceptibility; Antibiotics; Bacteria; Bacterial Interference; Bacteriuria; Benign; Benign Prostatic Hypertrophy; Bladder; Catheterization; Catheters; Chronic; Clinical Trials; Confocal Microscopy; Data; Drainage procedure; Effectiveness; Elderly; Escherichia coli; FDA approved; Failure; Future; Genes; Genetic; Goals; Hospitals; Host Defense; Human; In Vitro; Incidence; Individual; Indwelling Catheter; Infection; Left; Medicare; Microbial Biofilms; Microscopy; Monitor; Morbidity - disease rate; Neurogenic Bladder; Nursing Homes; Obstruction; Onset of illness; Organism; Pathogenesis; Persons; Pilum; Polysaccharides; Population; Predisposition; Prevention; Prevention strategy; Preventive; Probiotics; Protocols documentation; Pulsed-Field Gel Electrophoresis; Quality of life; Recurrence; Research Design; Resistance; Role; Safety; Secondary to; Serious Adverse Event; Societies; Sonication; Spinal cord injury; Surface; Testing; Tissues; United States; Urinary tract infection; Urine; Uropathogen; Virulence Factors; age related; antimicrobial drug; base; catheter associated UTI; experience; human subject; in vivo; novel; pathogen; pilot trial; prevent; primary outcome; prospective; randomized placebo controlled trial; safety study; success; superinfection; urinary

DESCRIPTION (provided by applicant): 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). PUBLIC HEALTH RELEVANCE: Catheter-associated urinary tract infection (CAUTI) is a recurrent problem for the many older individuals who require long-term urinary catheters for bladder drainage. This problem interferes significantly with individual quality of life and is costy to society, both in terms of the expense of treatment and in terms of the resistant organisms that arise through the treatment of CAUTI. We propose to use urinary catheters coated with benign (probiotic) bacteria as a means to prevent CAUTI without requiring the use of antibiotics.

描述（由申请人提供）：该提案解决了患有长期泌尿导管的个体中与导管相关的尿路感染（CAUTI）的慢性且昂贵的问题。这些人是长期的细菌性，尿道病的组织入侵会复发。我们对CAUTI的预防方法使用细菌干扰，因为我们故意接种了带有良性菌群的膀胱插座者，以防止病原体有症状的感染。这种新型的基于益生菌的方法避免使用抗菌剂，因此不会选择人类宿主菌群中的耐药性。该提案的总体目标是对涂有良性的尿导管试验试验 大肠杆菌（HU2117）的菌株作为接种长期尿导管老年人的膀胱的一种手段。大肠杆菌HU2117是野生型无症状细菌菌株大肠杆菌83972的衍生物，其中已删除了PILI的基因，从而阻止了这种可能的毒力因子的表达。我们以前已经使用大肠杆菌HU2117故意接种114名人类受试者的膀胱，其神经源性膀胱继发于脊髓损伤。 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将预测膀胱定殖和预防超感染的成功或失败。研究设计是一项前瞻性临床试验，在该试验中，所有20名受试者都会收到与大肠杆菌HU2117预先搭配的研究导管。受试者年龄> 50岁，取决于膀胱排水的长期导管，并具有基线细菌。研究导管将留在膀胱中28天，然后去除以进行微生物分析。受试者将伴随着连续尿培养物，直到大肠杆菌Hu2117从尿液中消失，并在12个月内发生严重的不良事件。 AIM 1的主要结果是安全性，CAUTI的率，殖民成功。安全性定义为没有受到症状性cauti或严重的不良事件的受试者，绝对与大肠杆菌HU2117有关。有症状的小肠的发生率将在用大肠杆菌HU2117定植之前，期间和之后记录。定殖成功定义为在研究​​导管插入后28天的尿液中存在大肠杆菌HU2117。对于AIM 2，将通过在殖民后，殖民后的序列尿培养物以及培养和显微镜研究中收集数据。目标2的目的是制定殖民成功和预防超级感染的预测规则。如果该试验试验成功，则结果将用于设计这些大肠杆菌涂层导管的随机，安慰剂对照试验，以防止CAUTI。试验方案已由FDA（IND＃14007）批准。 公共卫生相关性：对于许多需要长期尿导管以进行膀胱排水的老年人来说，与导管相关的尿路感染（CAUTI）是一个经常出现的问题。这个问题显着干扰了个人的生活质量，并且在治疗费用和通过治疗Cauti的抗药性生物方面对社会来说是昂贵的。我们建议使用涂有良性（益生菌）细菌的尿导管作为防止小肠菌的一种手段，而无需使用抗生素。