FACTORS PREDISPOSING TO URINARY TRACT INFECTIOUS

尿路感染的诱发因素

• 批准号: 3240131
• 负责人: WALTER E STAMM
• 金额: $ 24.65万
• 依托单位: UNIVERSITY OF WASHINGTON
• 依托单位国家: 美国
• 财政年份: 1989
• 资助国家: 美国
• 起止时间: 1989-03-01 至 1994-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3240131
• 关键词: Escherichia coli; bacteriuria; disease /disorder proneness /risk; drug adverse effect; epidemiology; female antifertility drug; human subject; microorganism classification; microorganism culture; nondrug contraceptive; sign /symptom; spermicide; urinary bladder epithelium; urinary tract infection; virulence

Preliminary data that we and others have collected suggests that diaphragm use may be associated with an increased risk of (1) E. coli vaginal colonization; (2) asymptomatic and symptomatic UTI; and (3) recurrent UTI. The prospective cohort study we propose is designed to confirm these associations in an optimal study design, and to investigate possible biological mechanisms through which diaphragm use predisposes to UTI. In addition, we will determine the interaction of diaphragm use with other factors thought to increase susceptibility to UTI in young women, specifically (i) sexual intercourse; (ii) specific E. coli virulence factors; and (iii) enhanced uroepithelial cell adherence. As diaphragm use may contribute to the causation of 30-40% of UTIs in young women and is a potentially reversible risk factor, these relationships are particularly important to study. We will accomplish the following specific aims: 1. In a prospective cohort study, compare 300 new diaphragm- spermicide users and 300 women initiating the use of spermicide alone with 300 new oral contraceptive users to determine the relative risk of asymptomatic bacteriuria (ASB) and symptomatic UTI in the first two groups. Compare diaphragm users who experience UTI with diaphragm users who do not in order to identify factors predisposing to UTI in this group. 2. Determine whether increased vaginal colonization with E. coli accompanies diaphragm-spermicide use by evaluating women just before first use and throughout the first month of use of each contraceptive method. Simultaneously assess the impact of each contraceptive method on the normal vaginal flora. Correlate changes in vaginal E. coli colonization with subsequent risk of ASB and symptomatic UTI. 3. Determine the presence and degree of urinary obstruction and post-void residual urine in diaphragm users, and the relationship of these variables to risk of ASB and UTI. 4. Determine whether vaginal and uroepithelial cells prospectively collected from women in each of the 3 groups demonstrate an increased ability to bind uropathogenic E. coli in an in vitro bacterial adherence assay as compared with cells collected from the same woman before the initiation of diaphragm, spermicide, or oral contraceptive use. Determine whether periods of increased epithelial cell adherence correlate temporally with vaginal E. coli colonization. 5. Characterize the E. coli strains causing ASB and UTI in diaphragm users, spermicide users and oral contraceptive users as to the presence or absence of bacterial properties associated with uropathogenicity, specifically serotype, hemolysin, aerobactin, type 1 fimbriae, P fimbriae and bacterial adherence. Determine rates of vaginal colonization with uropathogenic and non- uropathogenic E. coli, and the proportion of such colonization episodes that progress to ASB and UTI in each of the groups of women.

我们和其他人收集的初步数据表明 使用膜片可能与（1）E的风险增加有关。 大肠杆菌阴道定殖； （2）无症状和有症状的UTI； （3）经常性UTI。 我们提出的前瞻性队列研究是 旨在在最佳研究设计中确认这些关联， 并研究可能的生物学机制 膜片使用易于使用的UTI。 此外，我们将确定 隔膜使用与其他因素的相互作用 提高年轻女性对UTI的敏感性，特别是（i） 性交; （ii）特定的大肠杆菌毒力因子；和 （iii）增强的静脉细胞依从性。 随着隔膜的使用可能 在年轻妇女中促成30-40％的UTI的因果关系 是潜在的可逆风险因素，这些关系是 研究特别重要。 我们将完成以下内容 具体目的： 1。在一项前瞻性队列研究中，比较300个新的隔膜 - 杀精子剂使用者和300名妇女发起了精子剂的使用 单独使用300个新的口服避孕用户来确定 无症状细菌（ASB）和有症状性UTI的相对风险 在前两个组中。 比较体验的隔膜用户 与diaphragm用户的UTI无法识别因素 在这个组中倾向于UTI。 2。确定是否增加了大肠杆菌的阴道定植 通过评估女性，伴随着隔膜 - 胸膜剂的使用 在首次使用之前和整个使用者的第一个月 避孕方法。 同时评估每个的影响 正常阴道菌群的避孕方法。 相关 阴道大肠杆菌定植的变化，随后发生ASB的风险 和有症状的UTI。 3。确定尿阻塞的存在和程度 diaphragm用户中的尿后残留尿液和关系 在这些变量中冒着ASB和UTI的风险。 4。确定阴道和巨细胞是否前瞻性 从三个组中的每一个中收集的女性都表明 在体外结合尿素发育大肠杆菌的能力提高 细菌依从性测定与从 在启动隔膜，精子或口服之前的同一位妇女 避孕药使用。 确定是否增加 上皮细胞依从性与阴道大肠杆菌暂时相关 殖民化。 5。表征导致ASB和UTI的大肠杆菌菌株 diaphragm用户，杀精子用户和口服避孕用户作为 与与之相关的细菌特性的存在或不存在 肝病发育，特别是血清型，hemolysin，perobactin， 1型薄膜，p纤维和细菌粘附。 决定 与尿路病和非 - 的阴道定植率 肝癌大肠杆菌和这种定殖的比例 在每个组中都会发展为ASB和UTI的情节 女性。