DETERMINANTS OR URINARY TRACT INFECTIONS IN WOMEN

UTI每年影响700万妇女并导致大量发病率， 工作时间损失和医疗费用每年超过10亿美元。 E.大肠杆菌是一个关键的第一个 在这些感染的发病机制的步骤。初步数据显示， 收集到的证据表明阴道内的过氧化氢 产生乳酸杆菌防止E.杆菌和 尿路感染。因此，该项目的总体目标是描绘保护性的 产生H2O2的乳酸杆菌的作用， 阴道正常植物群，预防E.大肠杆菌阴道定植， 尿路感染。具体目标如下：（1）在前瞻性研究中， 对UTI治疗后随访4个月的女性进行研究，我们将 确定E.大肠杆菌阴道定植和UTI在那些 有和没有阴道产生H2O2的乳酸杆菌。(2)在同一 队列，我们将利用每日日记来识别特定暴露 （杀精剂，抗菌剂，性交，新伴侣，冲洗， 和其他），其降低阴道H2O2的患病率和数量 产生乳酸杆菌。(3)在随机试验中，我们将确定 是否用减少或消除UTI的抗微生物剂治疗 阴道产H202乳酸杆菌导致更频繁的复发 关于UTI (4)使用在1999年收集的菌株的分子特征， 通过前瞻性研究，我们将确定是否特异性尿毒力 基因或存在临时阴道H2O2产生性阴道炎 定植影响复发率。(5)我们将进行试点研究 以确定是否存在高粘附性的H2O2产生菌株， 卷曲乳杆菌作为阴道栓剂给予， 定殖E.杆菌拟议的研究将建立 产生H2O2的乳酸杆菌在预防UTI中的重要性， 找出影响正常的显性遗传的不利因素 植物群。一种高效阴道栓剂的研制 提供了一种预防尿路感染的新方法， 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.