MECHANISM OF CATHETER ASSOCIATED URINARY TRACT INFECTION

导管相关尿路感染的机制

基本信息

批准号：
8136160
负责人：
SATISH KUMAR
金额：
$ 18.06万
依托单位：
UNIVERSITY OF OKLAHOMA HLTH SCIENCES CTR
依托单位国家：
美国
项目类别：
财政年份：
2010
资助国家：
美国
起止时间：
2010-09-01 至 2012-08-31
项目状态：
已结题

项目摘要

DESCRIPTION: Urinary catheters are placed in one of four hospitalized patients. One in five catheterized patients develops catheter associated bacteriuria (CAB) that often progresses to catheter associated urinary tract infection (CAUTI). Patients with CAUTI have a 2.8 fold increase in mortality and account for 40% of all hospital acquired infections. Patients with CAB/CAUTI also provide a huge reservoir of drug resistant organisms in hospitals. The basic biological mechanisms of CAB and CAUTI are poorly understood. In particular the role of urinary host defense factors is poorly defined. Tamm-Horsfall Protein (uromodulin, THP) is urine's most abundant protein and has been shown to bind easily to a variety of surfaces and substances. THP has been demonstrated to act as a host defense factor against urinary tract infection (UTI), by binding bacteria in urine and clearing them before they can adhere to the urinary epithelium. The role of THP, if any, in CAB/CAUTI has not been studied. In this R21 application, we propose to test a new hypothesis that THP, which normally helps prevent UTI in the absence of a catheter, plays the opposite role of promoting UTI in the presence of a urinary catheter. THP binds to the catheter surface to form a conditioning layer. Bacteria adhere to THP on the catheter surface and form a biofilm under which they multiply to establish a reservoir that serves as a continuing source of bacteria in urine. Using in-vitro and animal studies, we will address 4 key questions: a) Does THP bind to urinary catheters? b) Does THP promote binding of bacteria to urinary catheters? c) Does THP facilitate formation of bacterial biofilm on urinary catheters? and d) Does the absence of THP increase or ecrease the risk of CAUTI? This proposal will test a new hypothesis about the role of THP in the pathogenesis of CAB and CAUTI. The data generated will point towards new strategies to combat CAUTI. PUBLIC HEALTH RELEVANCE: Infection of urinary catheters is a major problem in hospitals and nursing homes. The infected catheter makes the patient sick and is a source of infection for other patients. This proposal will research how urinary catheters get infected and will point towards preventive strategies against catheter infection.

描述：将尿导管放置在四名住院患者之一中。五分之一的导管插入患者会出现相关的导管菌尿（CAB），这些细菌尿液通常会发展为导管相关的尿路感染（CATI）。 CAUTI患者的死亡率增加了2.8倍，占所有医院感染的40％。患有CAB/CAUTI的患者在医院还提供了大量的耐药生物储藏。 CAB和CAUTI的基本生物学机制知之甚少。特别是，尿宿主防御因素的作用很差。 TAMM-HORSFALL蛋白（THP）是尿液最丰富的蛋白质，已被证明可以轻松结合各种表面和物质。已证明THP可以通过结合尿液中的细菌并清除它们在尿液上皮上的尿液中，是针对尿路感染（UTI）的宿主防御因素。尚未研究CAB/CAUTI中THP的作用。在此R21应用中，我们建议检验一种新的假设，即通常有助于在没有导管的情况下有助于防止UTI的THP在存在尿管存在下促进UTI的相反作用。 THP与导管表面结合以形成调节层。细菌粘附在导管表面上的THP并形成生物膜下，它们在其下繁殖以建立一个储层，该储层是尿液中持续的细菌来源。使用体外和动物研究，我们将解决4个关键问题：a）THP是否与尿导管结合？ b）THP是否促进细菌与尿导管的结合？ c）THP是否有助于在尿导管上形成细菌生物膜？ d）缺乏THP会增加或消除CAUTI的风险？该建议将检验一个关于THP在CAB和CAUTI发病机理中的作用的新假设。产生的数据将指出与Cauti作斗争的新策略。公共卫生相关性：尿导管的感染是医院和疗养院中的主要问题。感染的导管使患者生病，是其他患者感染的来源。该提案将研究尿导管如何感染，并指出针对导管感染的预防策略。