Evaluating linezolid for treating syphilis

Pilot Study of Linezolid for Early Syphilis Treatment

Phase 2 Interventional University of Southern California · NCT05548426

This study is testing if a new antibiotic called linezolid can effectively treat syphilis in people, including those with HIV, compared to the standard treatment with penicillin.

Quick facts

PhasePhase 2
Study typeInterventional
Enrollment24 (estimated)
Ages16 Years and up
SexAll
SponsorUniversity of Southern California Academic / other
Locations2 sites (Chicago, Illinois and 1 other locations)
Trial IDNCT05548426 on ClinicalTrials.gov

What this trial studies

This pilot trial aims to assess the efficacy of linezolid, administered at 600mg orally twice a day for either five or ten days, in treating syphilis. Participants will be randomly assigned to receive either linezolid or a single dose of benzathine penicillin G, with follow-ups to monitor clinical outcomes and serological responses at 1, 3, and 6 months. The study will include individuals with and without HIV infection, and aims to provide insights into alternative treatments for syphilis, especially in the context of penicillin shortages and allergies.

Who should consider this trial

Good fit: Ideal candidates include individuals aged 16 and older diagnosed with primary, secondary, or early latent syphilis.

Not a fit: Patients with pregnancy, certain psychiatric medication use, signs of neurosyphilis, or allergies to linezolid or penicillin may not benefit from this study.

Why it matters

Potential benefit: If successful, this study could provide an effective alternative treatment for syphilis, particularly for patients with penicillin allergies or those living with HIV.

How similar studies have performed: While this approach is novel in the context of syphilis treatment, other studies have explored linezolid for different infections, indicating potential for success.

Eligibility criteria

Show full inclusion / exclusion criteria
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

Where this trial is running

Chicago, Illinois and 1 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions SyphilisLinezolidTreponema pallidumPenicillinEarly Syphilis
Last reviewed 2026-06-13 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.