DETERMINANTS OR URINARY TRACT INFECTIONS IN WOMEN

女性尿路感染的决定因素

• 批准号: 6105833
• 负责人: WALTER E STAMM
• 金额: $ 19.33万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1999
• 资助国家: 美国
• 起止时间: 1999-02-15 至 2000-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6105833
• 关键词: Escherichia coli; Lactobacillus; antiinfective agents; bacteria infection mechanism; clinical research; clinical trials; communicable disease control; disease /disorder etiology; disease /disorder proneness /risk; drug adverse effect; female; genetic strain; human subject; hydrogen peroxide; longitudinal human study; microorganism metabolism; microorganism population study; personal log /diary; relapse /recurrence; restriction fragment length polymorphism; urinary tract infection; vagina; women's health

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.

UTI每年影响700万女性，并导致大量发病率， 下班损失的时间和医疗费用超过每年10亿美元。 与大肠杆菌的阴道浸血炎定殖是关键的第一 介入这些感染的发病机理。我们的初步数据 已经收集的表明阴道定植用过氧化氢殖民 产生乳酸杆菌可防止大肠杆菌和 UTI。因此，该项目的总体目标是描述保护性 H202产生乳杆菌的作用，乳酸杆菌是主要微生物种类 正常的阴道菌群，防止大肠杆菌阴道定植和 UTI。我们将完成以下具体目标：（1） 对UTI治疗后四个月的女性进行研究，我们将 确定其中大肠杆菌阴道定植和UTI的发生率 有和没有阴道H202产生乳杆菌。 （2） 队列，我们​​将利用每日日记来确定特定的暴露 （杀精子剂，抗菌素，性交，新伴侣，洗发， 和其他）减少阴道H202的患病率和数量 产生乳杆菌。 （3）在随机试验中，我们将确定 是否用减少或消除的抗菌药物处理UTI是 阴道H202产生乳杆菌会导致更频繁的复发 UTI。 （4）使用收集的菌株的分子表征 这项前瞻性研究，我们将确定是否具体的尿路 基因或临时阴道H202产生乳酸杆菌的存在 定殖影响复发率。 （5）我们将进行试点研究 确定高度粘附的H202是否产生 作为阴道栓剂的乳酸乳杆菌Crispatus可防止阴道 大肠杆菌定植。拟议的研究将确定 H202在防止UTI方面产生乳酸杆菌的重要性，并将 确定因素对正常乳杆菌的影响不利的因素 植物群。开发有效的阴道乳杆菌 提供了一种防止UTI的新方法，也可能具有重要的 对其他感染的影响。