From the Guidelines
Syphilis is treated with antibiotics, primarily penicillin, with the most recent and highest quality study 1 supporting the use of benzathine penicillin G as the preferred treatment for all stages of syphilis.
Treatment Regimens
The recommended treatment regimens are as follows:
- For early syphilis (primary, secondary, or early latent syphilis of less than one year's duration), a single intramuscular injection of benzathine penicillin G 2.4 million units is the recommended treatment.
- For late latent syphilis (infection of more than one year's duration) or syphilis of unknown duration, the recommended regimen is benzathine penicillin G 2.4 million units intramuscularly once weekly for three consecutive weeks.
- For neurosyphilis or ocular syphilis, aqueous crystalline penicillin G 18-24 million units daily, administered as 3-4 million units IV every 4 hours or continuous infusion for 10-14 days is recommended.
Alternative Treatments
For patients allergic to penicillin, doxycycline 100 mg orally twice daily for 14 days (early syphilis) or 28 days (late syphilis) can be used, though it's considered less effective 1.
Key Considerations
After treatment, follow-up blood tests are necessary to ensure the infection is cleared. Penicillin works by interfering with the cell wall synthesis of the Treponema pallidum bacterium that causes syphilis, ultimately killing the organism. Sexual partners should also be tested and treated if necessary, and patients should abstain from sexual activity until treatment is complete and follow-up testing confirms cure.
Recent Findings
Recent studies have provided additional reassurance about the efficacy of doxycycline or other tetracyclines for the treatment of early and late latent syphilis, suggesting that they are acceptable alternate agents when penicillin therapy is not feasible 1. However, concerns regarding macrolide resistance have led experts to agree that azithromycin should not be a recommended treatment for syphilis in the United States.
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.
- Doxycycline dosage for syphilis treatment:
- For early syphilis, the recommended dose is 100 mg, by mouth, twice a day for 2 weeks.
- For syphilis of more than one year’s duration, the recommended dose is 100 mg, by mouth, twice a day for 4 weeks.
- Important consideration: These dosages are for patients who are allergic to penicillin 2
From the Research
Treatment Options for Syphilis
- The primary treatment for early syphilis is benzathine penicillin G, with a single dose of 2.4 million units administered intramuscularly 3, 4, 5, 6.
- Azithromycin has been studied as a potential alternative treatment, with a single 2.0-g dose or two 2.0-g doses given 1 week apart showing promising results 3.
- Doxycycline is the preferred second-line treatment for early syphilis, with a 14-day course of 100 mg twice daily 4, 5, 7.
Efficacy of Treatment Options
- A study comparing benzathine penicillin G and azithromycin found cumulative response rates of 86% and 94%, respectively 3.
- A study comparing doxycycline and benzathine penicillin G found no statistically significant differences in serological responses at 6 and 12 months after treatment 5.
- Another study found that doxycycline had a slightly lower success rate compared to penicillin in treating primary syphilis, but appeared to have a reduced success rate in attaining resolution in late and undetermined syphilis infection 7.
Considerations for Treatment
- Patients with penicillin allergy or those who cannot receive penicillin may be treated with doxycycline or azithromycin 4, 6.
- Cerebrospinal fluid examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms 6.
- HIV-infected persons with syphilis may require enhanced treatment and monitoring 6.