E. coli for prevention of Catheter UTI in SCI Patients

尿路感染（UTI）是脊髓损伤（SCI）患者发病和死亡的主要原因。在复发性UTI患者中频繁使用抗微生物药物为耐药菌的发展创造了选择压力。因此，迫切需要设计和评估预防UTI的新方法。该项目的总体目标是开发一种新的方法，用于预防依赖留置导管进行膀胱引流的人的UTI。使用良性细菌来预防有症状的感染（如UTI）的概念被称为细菌干扰。我们先前证明，脊髓损伤患者膀胱内有意定植非致病性大肠杆菌菌株（83972）可降低症状性UTI的发生率。我们现在建议用E.大肠杆菌83972，然后插入病人的膀胱。我们的假设是，膀胱导管定植E。大肠杆菌83972，可以延迟病原菌附着到导管上，从而防止UTI。我们的初步研究表明，这可能是可行的。我们发现在体外培养的导尿管与E。大肠杆菌83972抑制随后的附着粪肠球菌，尿路致病性细菌。在本申请中，我们提出检测野生型和遗传增强的E.大肠杆菌83972抑制各种尿路病原体对导尿管的粘附，并对具有大肠杆菌预成型涂层的膀胱导尿管进行临床评价。大肠杆菌83972在人类受试者谁经历复发UTI作为长期导管插入的结果。拟议研究的结果可能最终使许多类型的需要留置膀胱导管进行尿液引流的活动障碍患者受益，包括SCI患者，脊柱裂儿童，中风患者和许多疗养院居民。这项研究将在休斯顿退伍军人事务医疗中心和贝勒医学院的脊髓损伤实验室进行。候选人计划将联合收割机在传染病方面的临床背景与在该奖项下进行的指导研究相结合，以减少移动障碍的继发感染并发症。

Urinary tract infection (UTI) is a major cause of morbidity and mortality in persons with spinal cord injury (SCI). Frequent use of anti-microbial agents in patients with recurrent UTI creates selection pressure for te development of resistant bacteria. Therefore, there exists a pressing need to design and evaluate new approaches for prevention of UTI. The overall goal of this project is to develop a new approach for prevention of UTI in persons who rely in indwelling catheters for bladder drainage. The concept of using benign bacteria to prevent symptomatic infection, such as UTI, is known as bacterial interference. We previously demonstrated that intentional colonization of the bladders of patients with spinal cord injury with a non-pathogenic strain of Escherichia coli (83972) reduced the frequency of symptomatic UTI. We now propose to extend this principle of bacterial interference by inoculating urinary catheters with E. coli 83972 prior to insertion into patients' bladders. It is our hypothesis that colonization of bladder catheters with E. coli 83972 prior to insertion into patients may delay attachment of pathogenic bacteria to the catheter and thereby prevent UTI. Our preliminary studies show that this may be feasible. We found in vitro that incubation of urinary catheters with E. coli 83972 inhibited subsequent attachment by Enterococcus faecalis, a uropathogenic bacterium. In the current application we propose to examine the capacity of both wild-type and genetically enhanced E. coli 83972 to inhibit catheter adherence by various uropathogens and to clinically evaluate bladder catheters with pre-formed coating of E. coli 83972 in human subjects who experience recurrent UTI as a result of long-term catheterization. The results of the proposed studies may eventually benefit many types of people with mobility disorders who require indwelling bladder catheters for urinary drainage, including persons with SCI, children with spina bifida, stroke victims, and many nursing home residents. The research will be done in the Spinal Cord Injury Laboratory at the Houston Veterans' Affairs Medical Center and at Baylor College of Medicine. The candidate plans to combine her clinical background in infectious diseases with the mentored research preformed under this award in order to reduce the secondary infectious complications of mobility disorders.