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.