What is the recommended treatment regimen for neurosyphilis?

Treatment Regimen for Neurosyphilis

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 Options

First-Line Therapy

• Aqueous crystalline penicillin G 18-24 million units per day, administered as 3-4 million units IV every 4 hours or continuous infusion, for 10-14 days 1, 2
• This regimen ensures penicillin concentrations in CSF continuously above the minimal treponemicidal concentration 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, though it results in lower CSF concentrations than IV administration 5

Special Considerations

Penicillin Allergy

• Patients with penicillin allergy should be treated in consultation with an infectious disease specialist 1
• Ceftriaxone 2 g daily either IM or IV for 10-14 days can be used as an alternative treatment, though cross-reactivity between ceftriaxone and penicillin exists 1, 2
• Limited evidence exists regarding the efficacy of ceftriaxone compared to penicillin G for neurosyphilis 6

Extended Treatment

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

HIV Co-infection

• HIV-positive patients with syphilis may have higher risk of neurological complications and higher rates of treatment failure 2, 7
• Standard high-dose penicillin regimens may not be consistently effective in HIV-infected patients 8
• All persons with syphilis should be tested for HIV 1, 2

Ocular Syphilis

• Syphilitic uveitis or other ocular manifestations should be managed according to the treatment recommendations for neurosyphilis 1
• Patients with syphilitic eye disease should be managed in collaboration with an ophthalmologist 1, 2
• A CSF examination should be performed for all patients with syphilitic eye disease 1

Follow-Up Monitoring

• If CSF pleocytosis was present initially, a CSF examination should be repeated every 6 months until the cell count is normal 1, 2
• The leukocyte count is a sensitive measure of the effectiveness of therapy 1, 2
• If the cell count has not decreased after 6 months or if the CSF cell count or protein is not normal after 2 years, retreatment should be considered 1, 7
• Limited data suggest that in immunocompetent persons and HIV-infected persons on highly active antiretroviral therapy, normalization of the serum RPR titer predicts normalization of CSF parameters 1

Treatment Pitfalls and Caveats

• Penicillin G benzathine alone (the standard treatment for early syphilis) is inadequate for neurosyphilis treatment 8
• Oral penicillin V does not achieve adequate CSF concentrations and should not be used for neurosyphilis 5
• Systemic steroids, although frequently used as adjunctive therapy for otologic syphilis, have not been proven to be beneficial 1
• Patients with cardiovascular syphilis may need to be treated with a neurosyphilis regimen in consultation with an infectious disease specialist 1