Linezolid for Syphilis Pilot Study

The two specific aims are: AIM 1: To evaluate the efficacy of linezolid compared to benzathine penicillin G in the treatment of syphilis. AIM 2: Evaluate the susceptibility of Treponema pallidum historical and novel strains to linezolid.

This will be a randomized, open-label, non-comparative, adaptive pilot trial to evaluate the efficacy of two linezolid oral dosing schemes (600mg orally, twice a day, for five or ten days) compared to the current recommendation for the treatment of syphilis, benzathine penicillin G (single dose of 2.4 million units) in participants with and without HIV infection. In total, 60 participants will be enrolled across 2 clinical sites in Peru. Participants will participate in follow-ups to monitor clinical outcomes and serological response (RPR titer) at 1 month, 3 months, and 6 months. The investigators will also test linezolid against several types of syphilis strains in the lab to evaluate the microbicidal activity of linezolid in treating early syphilis. Study findings may identify an efficacious alternative syphilis treatment to penicillin that is effective for people living with HIV. Study findings may also help address the crisis of penicillin shortages, difficulty in administration, and offer options for those with penicillin allergy.

Percentage of linezolid participants with a 4-fold decrease or greater in the serum RPR titer by 180 days after treatment

Determine the Minimum Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) of linezolid against 6 historical and 3 clinical isolated strains

Inclusion Criteria: 16 years of age or older Diagnosed cases of primary, secondary, or early latent syphilis with RPR titer ≥1:8 within 3 weeks prior to enrollment Able to provide informed consent For PLHIV: on treatment for HIV-infection and most recent viral load <200 copies/mL or most recent CD4 T-cell count >350 cells/mL Exclusion Criteria: Pregnancy or a positive pregnancy test on the day of enrollment Participants who receive certain psychotropic medications, e.g., MAO inhibitors, SNRIs, SSRIs Patients showing signs and symptoms of neurosyphilis Serofast RPR titer Recent (<7 days) or concomitant antimicrobial therapy with azithromycin, doxycycline, ceftriaxone, cefixime, or other beta lactam antibiotics (e.g. amoxicillin) Linezolid or penicillin allergy