Asymptomatic Bacteriuria & Risk of Urinary Tract Infection in Renal Transplants

描述（由申请人提供）：无症状细菌性尿症（ASB）是指从无尿路感染相关症状或体征的患者身上分离出一定数量的细菌。ASB在女性中很常见，并且随着年龄的增长而增加。有证据表明，ASB的治疗并不能预防症状性尿路感染（UTI），实际上可能导致尿路病原体抗生素耐药性的发生率增加，并发症的可能性更高。关于肾移植受者ASB的发生率，以及尿病菌表达的某些毒力因子是否会促进症状性尿路感染或急性同种异体肾移植损伤，问题仍然存在。在初步的回顾性研究中，我们发现大多数肾移植患者感染大肠杆菌尿路感染是无症状的。尽管没有尿路感染症状，一些肾移植患者合并ASB会出现膀胱炎、肾盂肾炎或急性肾损伤。从同种异体肾移植损伤的ASB患者中分离出的大多数细菌表达尿病P菌毛，这是一种促进细菌附着于尿上皮并可能导致有害炎症免疫反应的黏附素分子。此外，从肾移植患者的尿中分离出的大肠杆菌ASB通常对用于治疗尿路感染的常用抗菌药物具有耐药性。我们建议确定肾移植患者中ASB的患病率，并确定ASB分离株上表达的促进症状性尿路感染发展的宿主特征和细菌毒力因子。识别ASB患者中表达尿路致病因子的分离株将限制不适当的抗生素使用，减少尿路感染对同种异体肾移植功能的有害影响。这项研究的最终目的是确定ASB的筛查和治疗是否能预防症状性尿路感染和预防同种异体肾移植损伤。这项R21试点拨款的数据将成为肾移植患者ASB多中心临床试验设计的背景。该试验的信息将为肾移植人群中ASB的筛查和治疗提供急需的指导。公共卫生相关性：尿路感染（uti）是肾移植患者中最常见的感染，并与肾移植不良和患者生存相关。目前尚不清楚无症状尿路感染或无症状细菌尿（ASB）是否与肾移植患者出现症状性尿路感染或移植物功能障碍有关。美国传染病学会（IDSA）最近的指南承认，“对肾移植患者进行ASB筛查或治疗，不能提出支持或反对的建议”。需要研究确定肾移植患者中ASB的患病率、宿主特征、细菌毒力因素和与ABU相关的后果。

DESCRIPTION (provided by applicant): Asymptomatic bacteriuria (ASB) is the isolation of a specified quantity of bacteria from a person without symptoms or signs referableto urinary infection. ASB is common in women and increases with advancing age. There is some evidence that treatment of ASB does not prevent symptomatic urinary tract infection (UTI) and may actually lead to an increased incidence of uropathogen antibiotic resistance with a higher likelihood of complications. Questions remain as to incidence of ASB in the renal transplant recipient and whether certain virulence factors expressed on uropathic bacteria facilitate symptomatic UTI or acute renal allograft injury. In preliminary retrospective studies, we found that the majority of renal transplant patients with E. coli UTI are asymptomatic. Despite the lack of UTI symptoms, some renal transplant patients with ASB develop cystitis, pyelonephritis or acute kidney injury. The majority of the bacterial isolates from ASB patients with renal allograft injury express uropathic P fimbriae, an adhesin molecule that facilitates bacterial attachment to the uro-epithelium and may contribute to an injurious inflammatory immune response. In addition, the urinary isolates from renal transplant patients with E. coli ASB are frequently resistant to common antimicrobial agents used to treat UTI. We propose to determine the prevalence of ASB in renal transplant patients and to identify the host characteristics and bacterial virulence factors expressed on ASB isolates that facilitate the develop of symptomatic UTI. Identifying isolates from patients with ASB that express uropathogenic factors will limit inappropriate antibiotic use and decrease the deleterious effects of UTI on renal allograft function. The ultimate goal of this line of research is to determine if screening and treatment of ASB prevents symptomatic UTI and prevents renal allograft injury. Data from this R21 pilot grant will be the background for the design of a multi-center clinical trial of ASB in the renal transplant patient. Information from this trial would lead to a much needed screening and treatment guidelines for ASB in the renal transplant population. PUBLIC HEALTH RELEVANCE: Urinary tract infections (UTIs) are the most common infection in the kidney transplant patient and are associated with a poor kidney graft and patient survival. It is unclear if asymptomatic UTI, or asymptomatic bacteriuria (ASB), is associated with the development of symptomatic UTI or graft dysfunction in the renal transplant patient. Recent guidelines from the Infectious Disease Society of American (IDSA) acknowledge that "no recommendations can be made for or against screening or treatment of ASB in renal transplant patients". Studies are needed to determine the prevalence of ASB and the host characteristics, bacterial virulence factors and consequences associated with ABU in the renal transplant patient.