Treatment for Syphilis
Penicillin G is the treatment of choice for all stages of syphilis, with specific dosing regimens based on the stage of infection. 1
Treatment Regimens by Stage
Early Syphilis (Primary, Secondary, Early Latent)
- First-line treatment: Benzathine penicillin G 2.4 million units IM in a single dose 1
- Alternative for penicillin-allergic patients: Doxycycline 100 mg orally twice daily for 14 days 1, 2
Late Latent Syphilis or Latent Syphilis of Unknown Duration
- First-line treatment: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals 1
- Alternative for penicillin-allergic patients: Doxycycline 100 mg orally twice daily for 28 days 1, 2
Neurosyphilis
- First-line treatment: Penicillin G aqueous 18-24 million units IV daily, administered as 3-4 million units every 4 hours for 10-14 days 1
- Alternative: If unable to administer IV penicillin, some experts recommend ceftriaxone 2 g daily either IM or IV for 10-14 days
Special Populations
HIV-Infected Patients
- Treatment regimens are the same as for HIV-negative patients, but closer follow-up is required 3, 1
- Some specialists recommend additional weekly benzathine penicillin injections for early syphilis in HIV patients, though benefit remains unproven 3
Pregnant Women
- Penicillin is the only recommended treatment during pregnancy 1
- For penicillin-allergic pregnant women, desensitization followed by penicillin treatment is necessary 1
Penicillin Allergy Management
- For non-pregnant patients: Use doxycycline as specified above 1, 2
- For pregnant patients or those with neurosyphilis: Penicillin desensitization followed by appropriate penicillin therapy 1
Follow-up and Monitoring
- Non-treponemal tests (RPR or VDRL) should be repeated at 6,12, and 24 months after treatment 1
- Treatment failure is indicated by:
- Persistence or recurrence of signs/symptoms
- Sustained fourfold increase in non-treponemal test titers
- Failure to achieve fourfold decrease in titers within expected timeframe 1
Important Considerations
- Despite recent research on alternative treatments like azithromycin 4, 5, molecular resistance of T. pallidum to macrolides has been reported, limiting its use 3
- Recent benzathine penicillin G shortages have created challenges in syphilis management 6, making awareness of effective alternatives important
- A promising development is subcutaneous infusion of high-dose BPG, which may provide more sustained penicillin concentrations with less pain and fewer clinic visits 7
Contact Tracing and Prevention
- Sexual contacts exposed within 90 days of diagnosis of primary, secondary, or early latent syphilis should be treated presumptively 1
- Patients should be counseled on safer sex practices, including consistent condom use 1
Remember that while doxycycline has shown efficacy comparable to penicillin in some studies 8, penicillin remains the gold standard treatment with over 40 years of clinical experience supporting its use.