Tinidazole for the Treatment of Bacterial Vaginosis

描述(申请人提供)：细菌性阴道病(BV)是全世界最常见的阴道感染。它不仅会导致令人痛苦的症状，还会导致代价高昂的并发症，如早产、性病感染和艾滋病毒感染/传播。有人主张控制BV以减少这些并发症，但由于目前可用的治疗方案不足，这是不可行的。BV的特征是阴道菌群从以乳杆菌为主的菌群转变为高浓度的厌氧和兼性厌氧微生物。这种菌群变化的原因尚不清楚，尽管BV的流行病学与性行为高度相关。目前使用甲硝唑或克林霉素治疗BV的效果不佳，治愈率约为70%，复发率较高。替硝唑是一种与甲硝唑相关的抗生素，在全球范围内被广泛用于治疗寄生虫感染，但在美国还没有。欧洲的初步数据表明，可能由于其药代动力学特征，替硝唑治疗BV可能会导致显著更高的治愈率。我们建议通过在有症状的妇女中进行两种不同剂量的替硝唑和甲硝唑的临床试验来研究这一假设。此外，我们将在治疗期间测量阴道和血清中的药物浓度，并与治愈率、BV的短期复发和感染的严重程度相关。

DESCRIPTION (provided by applicant): Bacterial vaginosis (BV) is the most common vaginal infection worldwide. It not only causes distressing symptoms but also is associated with costly complications such as preterm birth, STD acquisition and HIV acquisition/transmission. Control of BV has been advocated for decreasing these complications, however this is not feasible due to the fact that currently available treatment regimens are inadequate. BV is characterized by a shift in the vaginal flora from a lactobacillus predominant flora to one in which there are high concentrations of anaerobic and facultative anaerobic organisms. The cause of this shift in flora remains unknown although the epidemiology of BV is highly linked to sexual behavior. Current treatments for BV with metronidazole or clindamycin are suboptimal with cure rates at approximately 70% and high recurrence rates. Tinidazole, which is an antibiotic related to metronidazole, is widely used worldwide for parasitic infections but is not available in the U.S. There is preliminary European data that suggest, perhaps due to its pharmacokinetic profile, that treatment with tinidazole could result in significantly higher cure rates for BV. We propose to study this hypothesis by conducting a clinical trial comparing two different dosing regimens of tinidazole to metronidazole among symptomatic women. In addition, we will measure vaginal and serum concentrations of drug during treatment and correlate with cure rates, short-term recurrence of BV, and severity of infection.