What is the recommended treatment for neurosyphilis?

Neurosyphilis Management

The recommended first-line treatment for neurosyphilis is aqueous crystalline penicillin G 18-24 million units per day, administered as 3-4 million units IV every 4 hours or as continuous infusion, for 10-14 days. 1, 2, 3

Primary Treatment Regimens

First-Line Therapy

• Aqueous crystalline penicillin G 18-24 million units per day, administered as 3-4 million units IV every 4 hours or as continuous infusion, for 10-14 days 1, 2, 3
• This regimen ensures adequate penetration into the cerebrospinal fluid (CSF) to achieve treponemicidal concentrations 4

Alternative Regimen

• Procaine penicillin 2.4 million units IM once daily PLUS probenecid 500 mg orally four times a day, both for 10-14 days 1, 2
• This alternative may be considered when IV administration is not feasible 1

Supplementary Treatment

• After completion of neurosyphilis treatment regimens, benzathine penicillin G 2.4 million units IM once weekly for up to 3 weeks can be considered to provide a comparable total duration of therapy to that used for late syphilis 1, 2

Management in Special Populations

Penicillin Allergy

• Ceftriaxone 2 g daily either IM or IV for 10-14 days can be used as an alternative treatment for patients with penicillin allergy 1, 2
• Caution should be exercised due to potential cross-reactivity between ceftriaxone and penicillin 1
• Consultation with an infectious disease specialist is recommended for patients with penicillin allergy 1

HIV Co-infection

• HIV-positive patients with syphilis may have higher risk of neurological complications and higher rates of serological treatment failure 2, 5
• The same treatment regimen is recommended, but closer follow-up may be necessary 5

Follow-Up Monitoring

• CSF examination should be repeated every 6 months until the cell count is normal if CSF pleocytosis was present initially 1, 2
• The leukocyte count is the most sensitive measure of treatment effectiveness 1, 6
• Consider retreatment if:
  • The CSF cell count has not decreased after 6 months 1, 6
  • The CSF cell count or protein is not normal after 2 years 1, 6

Additional Management Considerations

• All persons with syphilis should be tested for HIV 1, 2
• Patients with syphilitic eye disease (e.g., uveitis, neuroretinitis, optic neuritis) should be:
  • Treated with the recommended regimen for neurosyphilis 1, 2
  • Managed in collaboration with an ophthalmologist 1, 2
• CSF examination should be performed for all patients with syphilitic eye disease 1

Common Pitfalls and Caveats

• Inadequate penetration of penicillin into the CSF with non-IV regimens may lead to treatment failure 7
• Treatment failure can occur even with recommended high-dose IV penicillin regimens, particularly in HIV-infected patients 5
• Although systemic steroids are frequently used as adjunctive therapy for otologic syphilis, such drugs have not been proven to be beneficial 1
• The evidence comparing ceftriaxone to penicillin G for neurosyphilis is limited and of very low quality 8

The management of neurosyphilis requires careful attention to treatment regimens, follow-up monitoring, and consideration of special populations to ensure optimal outcomes and prevent complications.