From the Guidelines
Clinical treatment guidelines for syphilis recommend penicillin G as the first-line therapy for all stages of infection. For primary, secondary, or early latent syphilis (less than one year duration), a single intramuscular injection of benzathine penicillin G 2.4 million units is the standard treatment, as supported by the U.S. Centers for Disease Control and Prevention guidelines 1. For late latent syphilis (more than one year duration) or syphilis of unknown duration, three weekly doses of benzathine penicillin G 2.4 million units are recommended. Neurosyphilis requires a more intensive approach with aqueous crystalline penicillin G 18-24 million units daily, administered as 3-4 million units IV every 4 hours for 10-14 days.
Some key points to consider in the treatment of syphilis include:
- The importance of penicillin desensitization for pregnant women and neurosyphilis cases who are allergic to penicillin 1
- The use of alternative treatments such as doxycycline for penicillin-allergic patients, though desensitization to penicillin is preferred for pregnant women and neurosyphilis cases 1
- The need for follow-up serologic testing at 6,12, and 24 months after treatment to confirm cure, with declining nontreponemal test titers indicating successful treatment 1
- The evaluation and treatment of sexual partners from the past 90 days for primary syphilis, or the past year for secondary syphilis, to prevent further transmission 1
It's also important to note that while alternative treatments such as ceftriaxone may be considered for neurosyphilis in penicillin-allergic patients, the evidence for these alternatives is limited and penicillin remains the preferred treatment 1. Overall, the treatment of syphilis should be guided by the most recent and highest-quality evidence, with a focus on reducing morbidity, mortality, and improving quality of life for patients.
From the FDA Drug Label
Syphilis–early: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 2 weeks Syphilis of more than one year’s duration: Patients who are allergic to penicillin should be treated with doxycycline 100 mg, by mouth, twice a day for 4 weeks.
The recommended treatment guidelines for syphilis using doxycycline are as follows:
- For early syphilis, patients allergic to penicillin should take 100 mg of doxycycline orally, twice a day, for 2 weeks.
- For syphilis of more than one year’s duration, patients allergic to penicillin should take 100 mg of doxycycline orally, twice a day, for 4 weeks 2.
From the Research
Clinical Treatment Guidelines for Syphilis
- The preferred treatment for early syphilis is a single dose of 2.4 million units of benzathine penicillin G 3.
- Doxycycline is the preferred recommended second-line agent for the treatment of syphilis, with studies showing its effectiveness in treating early syphilis 4, 5.
- Azithromycin has been shown to be effective in treating syphilis, but its use is limited due to reports of azithromycin-resistant Treponema pallidum 3, 6.
- The treatment of neurosyphilis requires cerebrospinal fluid (CSF) examination and may require high-dose intravenous benzylpenicillin, especially in patients coinfected with HIV 3, 7.
Treatment Outcomes
- Studies have shown that doxycycline and benzathine penicillin G have similar serological response rates in the treatment of early syphilis 4, 5.
- Azithromycin has been shown to have similar cure rates to penicillin G benzathine in the treatment of early syphilis 6.
- Treatment failures in early syphilis have been rare, but may occur in patients coinfected with HIV 7.