Syphilis, Latent

The goal of this clinical trial is to learn if doxycycline taken as 200mg daily for 14 days is effective to treat early stage syphilis. This is different from how doxycycline is typically used for syphilis because the full doxycycline dose will be taken at the same time of day, rather than split up into a twice daily regimen. Lab data support that taking the medication as a single daily dose should be effective as treatment, but it has not been studied clinically. The main question this study aims to answer is:
Is doxycycline taken as a single daily dose of 200mg for 14 days an effective treatment for early syphilis based on a combined outcome of clinical improvement and blood test improvement?
Participants will:
1. Take doxycycline 200mg daily for 14 days
2. Submit oral and rectal swabs that test for syphilis bacteria every other day for 2 weeks, returned by mail
3. Complete 2 brief online surveys over the first 2 weeks
4. Return to the clinic for an interview and blood draw every 3 months for a maximum of 3 study visits, including the first visit
The investigators will compare the percentage of participants in the study who have response to treatment by 6 months to that of persons who have received standard (CDC-recommended) regimens. To do this, the investigators will calculate response percentage estimates following a shot of long-acting penicillin or 14 days of doxycycline 100mg twice daily from 60-person samples from the sexual health program's records.

According to European and US Centers for Disease Control and Prevention (CDC) guidelines, the recommended treatment for uncomplicated early syphilis in adults (i.e. primary, secondary and early latent) is a single intramuscular injection of 2.4 million units of benzathine benzylpenicillin G (BPG). Recent reviews have also recommended BPG as the first-line treatment of early syphilis, reporting a success rate of more than 90% over a large panel of studies. This form of the drug provides weeks of treponemicidal levels of penicillin in the blood, but does not efficiently cross the blood-brain barrier.
However, despite the use of BPG for almost 70 years and its status as the gold standard treatment for early syphilis, the need to administer this antibiotic parenterally has led to the use of second-line oral antibiotics, including firstgeneration macrolides, and then second-generation macrolides, such as azithromycin. Several African studies have shown 1 g azithromycin bid treatment for one day to be effective against early syphilis, but most authors agree that azithromycin should not generally be used as resistance to this macrolide is highly prevalent in Western countries. Moreover, a recent study by our group showed that more than 80% of the treponemal strains isolated in France harbor the mutation conferring resistance to azithromycin. The use of this alternative would, therefore, be highly unlikely to be effective in France. Tetracycline antibiotics have also been proposed as an alternative in patients with a contraindication for BPG or other forms of penicillin. Doxycycline, at a dose of 100 mg orally twice daily for 14 days, has been endorsed as a preferred alternative treatment, but few data are available concerning its efficacy. This issue is crucial, for two main reasons: there has been a recrudescence of early syphilis in most western countries over the last 20 years, increasing the need for BPG, and two periods of BPG shortage were experienced in 2013 and 2017, leading to the use of alternative treatments due to the temporary unavailability of BPG or its limitation to cases in which no other treatment was possible. Data for the manufacturing and distribution of antibiotics are not publicly available, but reports of limited availability, shortages, and price increases for old antibiotics suggest that the current system is too fragile to provide what should be a given in modern medicine: access to effective treatment for common and potentially severe bacterial infections. The recurrence of BPG shortages over the last five years has created an urgent need to demonstrate that doxycycline is safe, or at least as safe as BPG, for treating early syphilis. The investigators hypothesize that the recommended doxycycline regimen is not inferior to BPG and plan to test this hypothesis in a randomized clinical trial.

The Trep-AB clinical trial will test the efficacy of an investigational neuropenetrative drug, Linezolid (LZD), compared to standard treatment, Benzathine penicillin G (BPG), for early syphilis in humans. The overarching idea of the work proposed herein is to investigate the use of LZD to treat syphilis, conducting a randomized controlled clinical trial to evaluate this new indication of a known antibacterial agent.