Linezolid vs Penicillin for Syphilis

Recruiting at 1 trial location

Overseen By Jeffrey D Klausner, MD MPH

Age: Any Age

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: University of Southern California

Must not be taking: MAO inhibitors, SNRIs, SSRIs

Disqualifiers: Pregnancy, Neurosyphilis, Serofast RPR, others

No Placebo Group

Prior Safety Data

Approved in 4 Jurisdictions

Trial Summary

What is the purpose of this trial?

This trial is testing linezolid, an antibiotic taken by mouth, to treat syphilis. It includes people with and without HIV. Linezolid works by stopping bacteria from growing. The study aims to find an alternative to penicillin, especially for those who can't use it due to allergies or shortages.

Will I have to stop taking my current medications?

The trial requires that you stop taking certain psychotropic medications and any recent or current antibiotics like azithromycin, doxycycline, or penicillin-related drugs before joining.

Is Linezolid safe for humans?

Linezolid has been shown to be safe in humans, with no major adverse effects reported in a small number of human studies, although some adverse effects were observed in animal studies. ^{1 2 3 4 5}

How does the drug Linezolid differ from other treatments for syphilis?

Linezolid is unique because it is primarily used to treat bacterial infections like pneumonia and skin infections, and it works by stopping the growth of bacteria. Unlike penicillin, which is the standard treatment for syphilis, Linezolid is not typically used for this condition, making its use in this trial novel. ^{2 3 5 6 7}

Research Team

Jeffrey D Klausner, MD

Principal Investigator

University of Southern California

Eligibility Criteria

This trial is for individuals aged 16 or older diagnosed with primary, secondary, or early latent syphilis and have a recent RPR titer of at least 1:8. People living with HIV can join if they're on treatment and meet certain viral load or CD4 count criteria. Pregnant individuals, those on specific antibiotics or psychotropic meds, and anyone allergic to the study drugs cannot participate.

Inclusion Criteria

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

I am 16 years old or older.

Exclusion Criteria

Serofast RPR titer

Linezolid or penicillin allergy

I am showing signs of a brain or nerve condition caused by syphilis.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive linezolid 600mg orally, twice a day for either five or ten days

1-2 weeks

Follow-up

Participants are monitored for clinical outcomes and serological response (RPR titer) at 1 month, 3 months, and 6 months

6 months

3 visits (in-person)

Treatment Details

Interventions

• Linezolid (Oxazolidinone Antibiotic)

Trial Overview The study compares the effectiveness of two treatments for syphilis: Group A receives Penicillin (the standard treatment), while Group B gets Linezolid for 10 days. The goal is to see if Linezolid is an effective alternative.

Participant Groups

Group I: Linezolid 10 Day Experimental Treatment 1 Intervention

Oral linezolid 600mg, taken twice a day for 10 days

Group II: Benzathine Penicillin G Active Control 1 Intervention

Single intramuscular injection of 2.4 million units of benzathine penicillin G

Linezolid is already approved in Canada, Japan for the following indications:

Approved in Canada as Zyvox for:

• Complicated skin and skin structure infections
• Community-acquired pneumonia
• Nosocomial pneumonia

Approved in Japan as Zyvox for:

• Complicated skin and soft tissue infections
• Community-acquired pneumonia
• Nosocomial pneumonia

Who Is Running the Clinical Trial?

University of Southern California

Lead Sponsor

Trials

956

Recruited

1,609,000+

Universidad Peruana Cayetano Heredia

Collaborator

Trials

80

Recruited

62,300+

The University of Texas Health Science Center, Houston

Collaborator

Trials

974

Recruited

361,000+

Findings from Research

Ceftriaxone showed a higher serological response rate than penicillin at the 6-month follow-up in treating syphilis, suggesting it could be a viable alternative for patients allergic to penicillin.

While ceftriaxone was found to be equally effective as penicillin overall, further large-scale, high-quality trials are needed to confirm its safety and efficacy as a substitute for penicillin in syphilis treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Treatments for Different Stages of Syphilis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials and Observational Studies. Liu, M., Fan, Y., Chen, J., et al.[2023]

In a study involving 28 patients with primary or secondary syphilis, both ceftriaxone and penicillin G were found to be equally effective in treating the infection, as evidenced by a significant decline in VDRL titers and resolution of clinical symptoms.

Ceftriaxone was well-tolerated with no adverse reactions reported, while one patient experienced an allergic reaction to penicillin G, suggesting that ceftriaxone may be a safer alternative for some patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ceftriaxone for the treatment of primary and secondary syphilis. Schöfer, H., Vogt, HJ., Milbradt, R.[2018]

Benzathine penicillin remains the primary treatment for syphilis, as other options like clemizole and procaine penicillin are no longer available.

Alternative treatments such as doxycycline and ceftriaxone may be considered, but effective serological methods are essential to ensure the safety of the therapy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Current syphilis therapies and serological control. Commentary on the article by M. Hartmann in Hautarzt, Volume 2 (2004)]. Heise, H.[2018]

Linezolid has demonstrated effectiveness against syphilis in animal studies, suggesting it could be a potential alternative treatment amid shortages of benzathine penicillin.

The review found no teratogenic effects of linezolid, and while some adverse effects were noted in animal studies, no adverse effects were reported in a limited number of human studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety of Linezolid During Pregnancy. Navarro, S., Keith, K., Stafylis, C., et al.[2023]

A meta-analysis of seven randomized controlled trials involving 639 subjects found that azithromycin is as effective as penicillin for treating syphilis, with no significant differences in response rates at 3, 6, or 12 months.

The study indicates that azithromycin does not show inferior efficacy compared to penicillin, suggesting it could be a viable alternative treatment for syphilis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin vs penicillin G benzathine for early syphilis: A meta-analysis of randomized controlled trials. Li, Y., Jiang, G.[2021]

Azithromycin has been associated with treatment failures in syphilis due to a specific mutation in the Treponema pallidum bacteria that prevents the drug from effectively binding to its target, leading to increased resistance over time.

Despite the emergence of azithromycin resistance, Treponema pallidum remains sensitive to penicillin, highlighting the importance of using penicillin as the first-line treatment and the need for ongoing monitoring of antibiotic resistance.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Azithromycin resistance in Treponema pallidum. Katz, KA., Klausner, JD.[2022]

A retrospective analysis of 138 patients treated with 1.5 g/day amoxicillin for syphilis showed a high serological cure rate of 94.9%, indicating its effectiveness as a treatment option.

The treatment was well-tolerated, with only 1.5% of patients changing therapy due to adverse events, suggesting that amoxicillin without probenecid is a safe alternative for patients with and without HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical efficacy and tolerability of 1.5 g/day oral amoxicillin therapy without probenecid for the treatment of syphilis. Ikeuchi, K., Fukushima, K., Tanaka, M., et al.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Efficacy and Safety of Treatments for Different Stages of Syphilis: a Systematic Review and Network Meta-Analysis of Randomized Controlled Trials and Observational Studies. [2023]

2. Switzerland pubmed.ncbi.nlm.nih.gov

Ceftriaxone for the treatment of primary and secondary syphilis. [2018]

3. Germany pubmed.ncbi.nlm.nih.gov

[Current syphilis therapies and serological control. Commentary on the article by M. Hartmann in Hautarzt, Volume 2 (2004)]. [2018]

4. United States pubmed.ncbi.nlm.nih.gov

Safety of Linezolid During Pregnancy. [2023]

5. United States pubmed.ncbi.nlm.nih.gov

Azithromycin vs penicillin G benzathine for early syphilis: A meta-analysis of randomized controlled trials. [2021]

6. United States pubmed.ncbi.nlm.nih.gov

Azithromycin resistance in Treponema pallidum. [2022]

7. England pubmed.ncbi.nlm.nih.gov

Clinical efficacy and tolerability of 1.5 g/day oral amoxicillin therapy without probenecid for the treatment of syphilis. [2022]