What is the treatment for Syphilis?

From the Guidelines

Syphilis is treated with antibiotics, primarily penicillin, with the most effective regimen being a single intramuscular injection of benzathine penicillin G 2.4 million units for primary, secondary, or early latent syphilis. This treatment approach is supported by the Centers for Disease Control and Prevention (CDC) guidelines, as stated in the study published in the MMWR Recommendations and Reports in 2002 1. The guidelines recommend penicillin G, administered parenterally, as the preferred drug for treatment of all stages of syphilis.

For late latent syphilis or syphilis of unknown duration, the recommended regimen is benzathine penicillin G 2.4 million units intramuscularly once weekly for three consecutive weeks. Neurosyphilis is treated with aqueous crystalline penicillin G 3-4 million units intravenously every 4 hours for 10-14 days. In cases of penicillin allergy, doxycycline 100 mg orally twice daily for 14 days (early syphilis) or 28 days (late syphilis) can be used as an alternative, although it is less effective, as noted in the study published in the MMWR Recommendations and Reports in 2002 1.

Key considerations in the treatment of syphilis include:

• The stage of the disease
• The presence of any allergies, particularly to penicillin
• The patient's HIV status, as HIV-infected individuals may require more cautious management and closer follow-up
• The importance of follow-up blood tests at 3,6, and 12 months after treatment to ensure the infection has been successfully treated, as emphasized in the study published in the Annals of Internal Medicine in 2002 1.

Overall, the treatment of syphilis with penicillin, as recommended by the CDC and supported by clinical evidence, is effective in reducing morbidity, mortality, and improving quality of life for patients with this infection.

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:
  • Early syphilis: 100 mg, by mouth, twice a day for 2 weeks
  • Syphilis of more than one year’s duration: 100 mg, by mouth, twice a day for 4 weeks 2

From the Research

Syphilis Treatment Overview

• The primary treatment for syphilis is a single dose of 2.4 million units of benzathine penicillin G, as recommended by 3.
• This treatment is effective for early syphilis, with cure rates of 90-100% reported in studies 4.
• For individuals with HIV co-infection, the optimal treatment is still controversial, but penicillin G is recommended as the first-line therapy 4, 5.

Alternative Treatments

• Azithromycin has been studied as an alternative treatment for syphilis, with a single 2-g oral dose showing efficacy in treating early syphilis 6.
• However, the emergence of azithromycin-resistant Treponema pallidum has limited its use as a routine treatment option 3, 7.

Treatment Response and Follow-up

• After treatment, nontreponemal serologic titers should decline in a stable pattern, but some patients may remain seropositive (the "serofast state") 4.
• Serologic response to treatment should be evident by 6 months in early syphilis, but is generally slower (12-24 months) for latent syphilis 4.
• Cerebrospinal fluid (CSF) examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms, as well as in those who do not achieve a ≥ 4-fold serologic decline in their rapid plasma reagin (RPR) titers after adequate therapy 3.

Special Populations

• For HIV-infected individuals, CSF examination is recommended for those with syphilis of any stage whose RPR titers are ≥ 1:32 and/or whose CD4 cell counts are <350 cells/mm(3) 3.
• Pregnant women should be treated with penicillin G, as it is the recommended first-line therapy for syphilis in this population 4.