What is the recommended treatment for syphilis?

From the Guidelines

The recommended treatment for syphilis is penicillin G, specifically benzathine penicillin G administered as an intramuscular injection, as it remains the most effective treatment option according to the most recent and highest quality study 1.

Treatment Regimens

• For primary, secondary, or early latent syphilis (less than one year duration), a single dose of 2.4 million units is typically sufficient, as supported by the 2022 study 1.
• For late latent syphilis or syphilis of unknown duration, three doses of 2.4 million units given at one-week intervals is recommended, although the evidence for this is not as strong as for early syphilis 1.
• Neurosyphilis requires a more intensive approach with intravenous aqueous crystalline penicillin G for 10-14 days, as stated in the 2004 guidelines 1.

Alternative Treatments

• For patients with penicillin allergy, doxycycline (100 mg orally twice daily for 14-28 days) or tetracycline (500 mg orally four times daily for 14-28 days) may be used as alternative treatments, though these are considered less effective, as noted in the 2022 study 1.
• Azithromycin is not recommended due to concerns about macrolide resistance, as stated in the 2022 study 1.

Special Considerations

• Pregnant women with penicillin allergies should undergo desensitization and still receive penicillin treatment, as alternative antibiotics may not adequately treat the fetus, as recommended in the 2009 guidelines 1.
• Patients should be monitored with blood tests to confirm the infection is resolving, as this is a crucial step in ensuring effective treatment, although the specific details of this monitoring are not provided in the studies cited.

From the FDA Drug Label

All cases of penicillin treated syphilis should receive adequate follow-up including clinical and serological examinations. The recommended follow-up varies with the stage of syphilis being treated. Patients being treated for gonococcal infection should have a serologic test for syphilis before receiving penicillin.

The recommended treatment for syphilis is penicillin G, and adequate follow-up is necessary, including clinical and serological examinations. The follow-up recommendations vary depending on the stage of syphilis being treated. It is also important to perform a serologic test for syphilis before administering penicillin to patients being treated for gonococcal infection 2.

• Key points:
  • Penicillin G is the recommended treatment for syphilis
  • Adequate follow-up is necessary
  • Follow-up recommendations vary by stage of syphilis
  • Serologic test for syphilis is recommended before penicillin treatment for gonococcal infection

From the Research

Treatment of Syphilis

The recommended treatment for syphilis is a single dose of 2.4 million units of benzathine penicillin G, as stated by the Centers for Disease Control and Prevention 3. This treatment is effective for early syphilis, and a 3-dose regimen does not improve serological outcomes.

Alternative Treatments

Doxycycline is an alternative treatment for early syphilis, with a recommended dosage of 100 mg orally, twice daily for 14 days 4. Azithromycin is also an effective treatment, with a single dose of 2.0 g administered orally equivalent to benzathine penicillin G for the treatment of early syphilis in persons without HIV infection 5.

Key Considerations

• A single dose of benzathine penicillin G is the preferred treatment for early syphilis, regardless of HIV status 3, 6.
• Doxycycline and azithromycin are effective alternative treatments for early syphilis, but may not be suitable for all patients, such as those with HIV infection or neurosyphilis 4, 5.
• Cerebrospinal fluid examination should be performed in all persons with serologic evidence of syphilis infection and neurologic symptoms, and in those who do not achieve a ≥ 4-fold serologic decline in their rapid plasma reagin (RPR) titers after adequate therapy 6, 7.

Laboratory Focus

• Serological testing, including nontreponemal and treponemal-specific tests, is essential for the diagnosis of syphilis 7.
• Quantitative nontreponemal test titers should be obtained after treatment to monitor response to therapy, with a decline of fourfold expected within six months after treatment of primary or secondary syphilis, and within 12 to 24 months after treatment of latent or late syphilis 7.
• Cerebrospinal fluid examinations are necessary to ensure adequate treatment of neurosyphilis, with repeat examinations every 6 months until the cell count is normal 6, 7.