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）：本提案针对长期导尿管患者的导尿管相关性尿路感染（CAUTI）的慢性和昂贵问题。这些人患有慢性细菌尿症，并因尿路病原体侵入组织而复发。我们对CAUTI的预防方法使用细菌干扰，因为我们故意用良性菌群接种导管患者的膀胱，以防止病原体的症状感染。这种新的基于益生菌的方法避免了抗菌剂的使用，因此不会选择人类宿主菌群中的耐药性。本提案的总体目标是进行一项涂有良性肿瘤的导尿管的试点试验