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