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。反复尿路感染患者频繁使用抗菌药物为耐药细菌的发展创造了选择压力。因此，迫切需要设计和评估预防尿路感染的新方法。该项目的总体目标是开发一种新的方法来预防依赖留置导尿管进行膀胱引流的人的尿路感染。使用良性细菌来预防症状感染的概念被称为细菌干扰。我们先前证明，故意用非致病性大肠杆菌(83972)定植脊髓损伤患者的膀胱可以减少有症状的尿路感染的频率。我们现在建议通过在导尿管插入患者膀胱之前接种大肠杆菌83972来扩展这一细菌干扰的原理。我们的假设是，在将膀胱导管插入患者体内之前，在膀胱导管中定植大肠杆菌83972可能会延迟致病菌附着到导管上，从而防止尿路感染。我们的初步研究表明，这可能是可行的。我们在体外发现，将导尿管与大肠杆菌83972孵育可抑制粪肠球菌的附着，粪肠球菌是一种泌尿病原菌。在目前的应用中，我们建议检测野生型和基因增强型大肠杆菌83972抑制各种泌尿病原体对导尿管粘连的能力，并在临床上评估因长期导尿而复发的受试者身上预制有大肠杆菌83972涂层的膀胱导尿管。拟议的研究结果最终可能使需要留置膀胱导管进行尿流的许多类型的活动障碍患者受益，包括脊髓损伤患者、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的脊髓损伤实验室和贝勒医学院进行。候选人计划将她在传染病方面的临床背景与该奖项下进行的指导研究相结合，以减少行动不便的继发性感染并发症。

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.