Pilot study of linezolid for early syphilis treatment

项目摘要 拟议的试点项目将评估利奈唑胺治疗早期梅毒的疗效。梅毒发病率 在美国和国际上都在增加。在与男性发生性关系的男性中发病率更高 感染艾滋病毒的个人。目前，注射用青霉素用于治疗梅毒；然而，注射用青霉素 在许多国家是不可用的。强力霉素、四环素和头孢曲松是治疗非霍奇金淋巴瘤的替代疗法 对青霉素过敏的孕妇。尽管现有的治疗方案是基于临床 根据经验，目前有数量有限的小型临床试验和病例系列。每种非青霉素治疗 给给药和依从性带来了临床挑战。改变已获批准的安全抗生素的用途 可以更快地将新的、安全和有效的抗生素治疗方案引入临床，并减少 开发成本。这一试点项目的重点是研究FDA批准的抗生素的潜在疗效 利奈唑胺。 在这项建议中，我们将测试利奈唑胺的临床疗效和杀菌活性，以确定其作为一种 梅毒治疗。我们将在我们成功的梅毒临床研究的基础上，进行随机、开放的- 评估两种利奈唑胺剂量方案(600 mg，每日两次， 10天或5天)。我们将从两个临床地点招募60名患有早期梅毒的参与者 秘鲁。我们将跟踪参与者监测临床进展和血清学反应(RPR滴度)在7，30， 90天、180天、270天和360天。我们的假设是利奈唑胺对治疗早期梅毒有效。 从登记到治疗后三或六个月，RPR滴度下降了四倍 给药和对多个梅毒螺旋体分离物的杀菌活性。 我们建议的两个具体目标是：目标1：评价利奈唑胺治疗早期糖尿病的疗效。 梅毒。目的：评价梅毒螺旋体历史株和新株对利奈唑胺的敏感性。 这个为期两年的项目分为四个阶段。第一阶段为期四个月，将涉及研究的发展 在招聘、登记和数据收集方面的工具和工作人员培训。第二阶段将持续12个月， 将涉及患者的招募和登记以及临床标本的收集。第三阶段将持续24小时 几个月，但将与第二阶段同步进行，并包括患者随访期。第四阶段将 过去三个月，包括数据分析和传播。

PROJECT ABSTRACT The proposed pilot project will evaluate the efficacy of linezolid in the treatment of early syphilis. Syphilis rates are increasing both in the US and internationally. Incidence is higher among men who have sex with men and in individuals with HIV infection. Currently, injectable penicillin is used to treat syphilis; however, injectable penicillin is not available in many countries. Doxycycline, tetracycline, and ceftriaxone are alternative treatments for non- pregnant patients who are allergic to penicillin. Although existing treatment alternatives are based on clinical experience, there are a limited number of small clinical trials and case series. Each non-penicillin treatment poses clinical challenges for administration and compliance. Repurposing already approved and safe antibiotics could bring new, safe, and efficacious antibiotic treatment options into the clinic faster and cut down on development costs. This pilot project focuses on studying the potential efficacy of the FDA-approved antibiotic linezolid. In this proposal, we will test the clinical efficacy and microbicidal activity of linezolid to establish its use as a syphilis treatment. We will build upon our successful syphilis clinical studies to conduct a randomized, open- label, non-comparative pilot study to evaluate the efficacy of two linezolid dosing schemes (600mg, twice a day, for ten days or for five days) in patients. We will enroll 60 participants with early syphilis from two clinical sites in Peru. We will follow the participants to monitor clinical progress and serological response (RPR titer) at 7, 30, 90, 180, 270 and 360 days. Our hypothesis is that linezolid will be efficacious in treating early syphilis demonstrated by four-fold decrease in RPR titer, from enrollment to three or six months after treatment administration, and by microbicidal activity against multiple Treponema pallidum isolates. The two specific aims of our proposal are: AIM 1: To evaluate the efficacy of linezolid for the treatment of early syphilis. AIM 2: Evaluate the susceptibility of Treponema pallidum historical and novel strains to linezolid. The two-year project has four phases. Phase I will last four months and will involve the development of study instruments and staff training on recruitment, enrollment, and data collection. Phase II will last 12 months and will involve recruitment and enrollment of patients and collection of clinical specimens. Phase III will last 24 months, but will proceed simultaneously with Phase II, and include the patient follow-up period. Phase IV will last three months and includes data analysis and dissemination.