From the Guidelines
The recommended treatment for syphilis is primarily penicillin G, with the specific regimen depending on the stage 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 most recent guidelines 1.
Key Considerations
- For late latent syphilis (more than one year duration) or syphilis of unknown duration, the recommended regimen is benzathine penicillin G 2.4 million units intramuscularly once weekly for three consecutive weeks.
- Neurosyphilis requires a more intensive approach with aqueous crystalline penicillin G 18-24 million units daily, administered as 3-4 million units intravenously every 4 hours for 10-14 days.
- For penicillin-allergic patients who don't have neurosyphilis, alternatives include doxycycline 100 mg orally twice daily for 14 days (primary/secondary) or 28 days (late latent), or tetracycline 500 mg orally four times daily for the same durations, as suggested by earlier guidelines 1.
Special Populations
- Pregnant women with penicillin allergies should undergo desensitization as penicillin is the only proven effective therapy during pregnancy.
- Patients should be monitored with follow-up serologic tests at 6 and 12 months after treatment.
- Sexual partners from the past 90 days for primary syphilis, 6 months for secondary syphilis, or 1 year for early latent syphilis should be notified, tested, and treated.
Rationale
Penicillin remains the treatment of choice because Treponema pallidum, the causative bacterium, is consistently sensitive to it, and the long-acting formulation maintains treponemicidal levels for extended periods, as consistently recommended across guidelines 1.
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 regimen for syphilis is as follows:
- For early syphilis, patients allergic to penicillin should take doxycycline 100 mg orally, twice a day, for 2 weeks.
- For syphilis of more than one year's duration, patients allergic to penicillin should take doxycycline 100 mg orally, twice a day, for 4 weeks 2.
From the Research
Syphilis Treatment Regimens
The recommended treatment regimen for syphilis is primarily based on the stage of the disease.
- For early syphilis, the primary recommended treatment is intramuscular benzathine penicillin G (BPG) 3.
- Alternative treatments have been studied, including azithromycin and doxycycline, which have shown promise in treating early syphilis 4, 5, 6.
Treatment Options
- Benzathine penicillin G (BPG) is the only medication currently recommended for treatment of early syphilis in non-penicillin-allergic patients 4.
- Azithromycin has been studied as an alternative treatment, with a single 2.0-g dose or two 2.0-g doses given 1 week apart showing cumulative response rates of 94% and 83%, respectively 4.
- Doxycycline is the preferred recommended second-line agent for the treatment of syphilis, with efficacy data from controlled trials showing serological cure rates comparable to BPG 5.
Special Considerations
- In cases where BPG is not available, alternative treatments such as doxycycline may be used 3.
- The treatment of late latent syphilis has been studied, with benzathine penicillin G (2.4 X 10(6) units given intramuscularly once a week for two weeks) showing serological response rates of 44% becoming seronegative within five years 7.