What is the treatment for syphilis?

From the Guidelines

Penicillin G is the recommended treatment for syphilis at all stages. The treatment regimen for syphilis depends on the stage and clinical manifestations of the disease.

Treatment Regimens

• 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 standard treatment 1.
• 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, the treatment is aqueous crystalline penicillin G 3-4 million units intravenously every 4 hours for 10-14 days.

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 less effective.

Rationale

Penicillin remains the drug of choice because the causative organism, Treponema pallidum, is highly sensitive to it, and penicillin effectively crosses the blood-brain barrier to treat potential central nervous system involvement 1.

Follow-up

Follow-up blood tests are essential to confirm treatment success, typically at 3,6, and 12 months after treatment. The most recent and highest quality study 1 supports the use of penicillin as the first-line treatment for syphilis, and this recommendation is based on the strongest available evidence.

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 treatment for syphilis with doxycycline is:

• 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

Treatment Options for Syphilis

• The primary recommended treatment for early-stage syphilis is intramuscular (IM) benzathine penicillin G (BPG) 3, 4.
• Alternative treatments include doxycycline, which can be used in cases where BPG is unavailable 3, 4.
• Azithromycin has shown promise as a potential treatment for syphilis, with studies indicating high response rates 5.
• Other antibiotics, such as tetracyclines and erythromycin, may be used as alternatives to penicillin, but have limitations due to frequent adverse effects and unproven efficacy for central nervous system involvement 6, 7.
• Ceftriaxone has also been evaluated as a potential treatment for early syphilis, but the optimal dose and duration of therapy are unknown 7.

Administration and Follow-up

• Benzathine penicillin G is typically administered as a single injection or a course of daily procaine penicillin injections for 10 to 14 days 4.
• Follow-up is an essential part of management, particularly in patients co-infected with HIV, and should be continued for at least 24 months 4.
• Partner notification is also crucial in preventing the spread of infection 4.

Special Considerations

• In cases of penicillin allergy, alternative treatments such as doxycycline or azithromycin may be used 5, 4.
• Patients with neurological or ocular signs, psychiatric signs or symptoms, or evidence of treatment failure may require examination of the cerebrospinal fluid and alternative treatment regimens 4.