Pilot study of linezolid for early syphilis treatment

利奈唑胺治疗早期梅毒的初步研究

• 批准号: 10575509
• 负责人: Jeffrey David Klausner
• 金额: $ 23.72万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-11-22 至 2024-10-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10575509
• 关键词: Address; Adherence; Adult; Aftercare; Allergic; Animals; Antibiotic Therapy; Antibiotics; Bacteria; Benzathine Penicillin; Case Series; Cefixime; Ceftriaxone; Cephalosporins; Cerebrospinal Fluid; Clinic; Clinical; Clinical Research; Clinical Trials; Collection; Control Groups; Country; Data; Data Analyses; Data Collection; Development; Dose; Doxycycline; Drug Kinetics; Drug resistance in tuberculosis; Early treatment; Enrollment; FDA approved; Funding; Generations; Globus Pallidus; Gram-Positive Bacteria; HIV Infections; Hour; Human; Hypersensitivity; In Vitro; Incidence; Individual; Infectious Skin Diseases; Injectable; Injections; International; Intramuscular; Lesion; Linezolid; Minimum Inhibitory Concentration measurement; Modeling; Monitor; Oral; Oral Administration; Oral cavity; Oryctolagus cuniculus; Outcome; Oxazolidinones; Participant; Patients; Penicillin Allergy; Penicillin G; Penicillins; Persons; Peru; Phase; Pilot Projects; Pneumonia; Predisposition; Pregnancy; Randomized; Randomized, Controlled Trials; Recommendation; Regimen; Research; Safety; Sampling; Scheme; Serology; Serology test; Site; Specimen; Streptococcus; Syphilis; System; Testing; Tetracyclines; Time; Toxic effect; Training; Treponema pallidum; United States National Institutes of Health; Vancomycin resistant enterococcus; Work; alternative treatment; arm; bactericide; clinical efficacy; clinical research site; cost; data dissemination; effective therapy; efficacy evaluation; experience; experimental arm; experimental study; follow-up; healing; instrument; men who have sex with men; methicillin resistant Staphylococcus aureus; microbicide; novel; novel strategies; open label; participant enrollment; pilot trial; recruit; research clinical testing; response; success; treatment duration

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.

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。西地拉提斯 在美国和国际上都在增长。男性同性性行为者的发病率较高， 艾滋病毒感染者。目前，可注射青霉素用于治疗梅毒;然而， 在很多国家都没有。多西环素、四环素和头孢曲松是非- 对青霉素过敏的孕妇虽然现有的治疗方案是基于临床 根据经验，小型临床试验和病例系列数量有限。每次非青霉素治疗 对给药和依从性提出了临床挑战。重新使用已批准的安全抗生素 可以更快地为临床带来新的，安全的，有效的抗生素治疗选择， 开发成本。该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。 在本提案中，我们将测试利奈唑胺的临床疗效和杀微生物活性，以确定其作为 梅毒治疗我们将在我们成功的梅毒临床研究的基础上，进行一项随机、开放的- 评价两种利奈唑胺给药方案（600 mg，每日两次， 10天或5天）。我们将从两个临床研究中心招募60名早期梅毒患者， 秘鲁。我们将在7、30、40、50、60、70、80、90、100、200、 90、180、270和360天。我们的假设是利奈唑胺将有效治疗早期梅毒 从入组至治疗后3个月或6个月，RPR滴度下降4倍 施用，并通过对多种梅毒螺旋体分离株的杀微生物活性。 我们建议的两个具体目标是：目的1：评价利奈唑胺治疗早期 梅毒目的2：评价梅毒螺旋体历史株和新株对利奈唑胺的敏感性。 该项目为期两年，分为四个阶段。第一阶段将持续四个月， 工具和人员招募、入组和数据收集培训。第二阶段将持续12个月， 将涉及患者招募和入组以及临床标本采集。第三阶段将持续24 个月，但将与II期同时进行，并包括患者随访期。第四阶段将 三个月，包括数据分析和传播。