DETERMINANTS OR URINARY TRACT INFECTIONS IN WOMEN

尿路感染每年影响700万妇女，并导致大量发病率， 每年因工作损失的时间和超过10亿美元的医疗费用。 感染大肠杆菌的阴道内膜炎的定植是一个关键的第一步 在这些感染的发病机制中迈出了一步。初步数据显示，我们 已经收集到的证据表明，双氧水在阴道内定植 生产乳酸菌可预防阴道内大肠杆菌和 UTI。因此，该项目的总体目标是勾勒出 产H_202乳酸菌的作用 正常的阴道菌群，在防止大肠杆菌阴道定植和 UTI。我们将实现以下具体目标：(一)着眼于 对女性尿路感染治疗后四个月的研究，我们将 确定大肠埃希氏菌阴道定植和泌尿系感染的发生率 有和没有阴道H202产生乳酸菌。(2)在相同的 队列，我们将利用日常日记来确定特定的接触情况 (杀精剂、抗菌剂、性交、新伴侣、冲洗、 和其他)，以降低阴道H202的患病率和数量 产生乳酸菌。(3)在随机试验中，我们将确定 是否使用减少或消除的抗菌药治疗尿路感染 阴道产生H202乳酸杆菌导致更频繁的复发 UTI的。(4)利用收集到的菌株的分子特征 这项前瞻性研究，我们将确定特定的尿毒力 基因或临时性阴道产H202乳杆菌的存在 移居会影响复发率。(五)我们会进行先导研究 为了确定一株高粘附性的H202产生菌 皱纹乳杆菌作为阴道栓使用可预防阴道 用大肠杆菌进行定植。建议的研究将确立 H202产乳酸菌在预防尿路感染中的重要性 确定影响正常优势乳酸菌的不利因素 弗洛拉。高效乳酸菌阴道栓的研制 提供了一种预防尿路感染的新方法，也可能具有重要的 对其他感染的影响。

UTIs affect 7 million women each year and result in substantial morbidity, time lost from work and medical costs exceeding $1 billion per annum. Colonization of the vaginal introitis with E. coli is a critical first step in the pathogenesis of these infections. Preliminary data that we have collected suggest that vaginal colonization with hydrogen peroxide producing lactobacilli prevents both vaginal colonization with E. coli and UTI. The overall goal of this project is thus to delineate the protective role of H202 producing lactobacilli, the principal microbial species of the normal vaginal flora, in preventing E. coli vaginal colonization and UTI. We will accomplish the following specific aims: (1) In a prospective study of women followed for four months after treatment for UTI, we will ascertain the incidence of E. coli vaginal colonization and UTI in those with and without vaginal H202 producing lactobacilli. (2) In the same cohort, we will utilize daily diaries to identify specific exposures (spermicide, antimicrobials, sexual intercourse, new partner, douching, and others) that reduce the prevalence and quantity of vaginal H202 producing lactobacilli. (3) In a randomized trial, we will determine whether treatment of UTI with antimicrobials that reduce or eliminate vaginal H202 producing lactobacilli results in more frequent recurrences of UTI. (4) Using molecular characterization of the strains collected in the prospective study, we will determine whether specific urovirulence genes or the presence of interim vaginal H202 producing lactobacillus colonization affects recurrence rates. (5) We will perform a pilot study to determine whether a highly adherent H202 producing strain of Lactobacillus crispatus given as a vaginal suppository prevents vaginal colonization with E. coli. The proposed studies will established the importance of H202 producing lactobacilli in preventing UTI, and will identify factors adversely influencing the normal lactobacillus dominant flora. Development of an effective lactobacillus vaginal suppository offers a new approach to preventing UTIs, and could also have important implications for other infections.