What is syphilis?

From the Guidelines

Syphilis should be treated with Benzathine penicillin G, with the specific regimen depending on the stage of the disease, to prevent long-term complications and reduce morbidity and mortality. The treatment for syphilis is based on the stage of the disease, with early syphilis (primary, secondary, or early latent syphilis of less than one year's duration) typically treated with a single intramuscular injection of Benzathine penicillin G 2.4 million units 1. 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 1.

Some key points to consider when treating syphilis include:

• Patients allergic to penicillin may be treated with doxycycline 100 mg orally twice daily for 14 days (early syphilis) or 28 days (late syphilis), though this is less effective 1
• All sexual partners from the past 90 days should be notified, tested, and treated if necessary 1
• Follow-up blood tests are essential at 3,6, and 12 months after treatment to ensure cure 1
• Syphilis progresses through stages if untreated: primary (painless ulcer or chancre), secondary (rash, fever, lymphadenopathy), latent (asymptomatic), and tertiary (severe organ damage) 1
• Penicillin remains highly effective because T. pallidum has not developed resistance, and it penetrates well into tissues where the bacterium hides 1
• Pregnant women with syphilis must be treated promptly with penicillin to prevent congenital syphilis in the baby 1

It is also important to note that patients with latent syphilis should have careful examination of all accessible mucosal surfaces to evaluate for internal mucosal lesions, and all patients who have syphilis should be tested for HIV infection 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.

• Doxycycline dosage for syphilis:
  • 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
• Key points:
  • Doxycycline is used as an alternative treatment for patients allergic to penicillin
  • The dosage and duration of treatment vary depending on the stage of syphilis 2

From the Research

Syphilis Treatment

• The recommended treatment for early syphilis is a single dose of 2.4 million units of benzathine penicillin G 3.
• Enhanced antibiotic therapy has not been shown to improve treatment outcomes, regardless of human immunodeficiency virus (HIV) status 3.
• Azithromycin has been studied as an alternative treatment for early syphilis, but its use is limited due to reports of resistance 4, 5.
• A systematic review of treatment regimens for syphilis found that penicillin is the mainstay of treatment, despite limited clinical trial data 6.

Treatment Outcomes

• Treatment success rates for early syphilis with benzathine penicillin G are reported to be 90-100% 6.
• Cure rates for primary and secondary syphilis treated with standard therapy were 98%, compared to 92% with enhanced therapy 7.
• HIV-infected individuals had cure rates of 88% after a single dosage, compared to 97% after three dosages of benzathine penicillin G 7.

Special Considerations

• Cerebrospinal fluid (CSF) examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms 3.
• HIV-infected persons with syphilis of any stage whose RPR titers are ≥ 1:32 and/or whose CD4 cell counts are <350 cells/mm(3) may be at increased risk for asymptomatic neurosyphilis 3.
• Pregnant women should be treated with penicillin as first-line therapy 6.