Neurosyphilis medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1];Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]

Overview

Medical therapy is recommended for all patients diagnosed with neurosyphilis. Penicillin is the treatment of choice for neurosyphilis. CNS involvement can occur during any stage of syphilis. However, CSF laboratory abnormalities are common in persons with early syphilis, even in the absence of clinical neurological findings. Syphilitic uveitis or other ocular manifestations frequently are associated with neurosyphilis and should be managed according to the treatment recommendations for neurosyphilis.

Management of Neurosyphilis

For patients diagnosed with neurosyphilis including ocular or auditory syphilis with or without positive CSF results, aqueous crystalline penicillin G is the treatment of choice.

• The recommended regimen is intravenous administration of penicillin every 4 hours or continuously for 10-14 days.
  • Oral antibiotics are not recommended for the treatment of neurosyphilis.
  • If  aqueous crystalline penicillin G is contraindicated, then procaine penicillin is an alternative (administered daily with probenecid for two weeks).
  • Intramuscular ceftriaxone for 14 days is also shown to be an alternative effective.

Pharmacotherapy

• Preferred regimen (1): 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.

• Alternative regimen (1): Procaine penicillin 2.4 million units IM once daily, plus probenecid 500 mg orally four times a day, both for 10-14 days.
• Alternative regimen (2): Benzathine penicillin G 2.4 million units IM once per week for up to 3 weeks after regular course.
  • To approximate for late latent disease and to address concerns about slowly dividing treponemes.

Other Management Considerations

• Other considerations in the management of patients who have neurosyphilis are as follows:

• All persons who have syphilis should be tested for HIV.
• Although systemic steroids are used frequently as adjunctive therapy for otologic syphilis, such drugs have not been proven to be beneficial.

Special Considerations

Penicillin Allergy: Alternative Regimen

• Limited data suggest that ceftriaxone 2 g daily either IM or IV for 10-14 days can be used as an alternative treatment for patients with neurosyphilis.

• The possibility of cross-reactivity between ceftriaxone and penicillin exists.

• Other regimens have not been adequately evaluated for treatment of neurosyphilis. Therefore, if concern exists regarding the safety of ceftriaxone for a patient with neurosyphilis, skin testing should be performed (if available) to confirm penicillin allergy and, if necessary, desensitize the patient.

Pregnancy:

• Pregnant patients who are allergic to penicillin should be desensitized and treated with penicillin.

Neurosyphilis Among HIV-Infected Persons:

• HIV-infected patients with neurosyphilis should be treated according to the recommendations for HIV-negative patients with neurosyphilis.

• HIV-infected, penicillin-allergic patients who have neurosyphilis should be managed according to the recommendations for penicillin-allergic, HIV-negative patients with neurosyphilis.

• Several small observational studies conducted in HIV-infected patients with neurosyphilis suggest that ceftriaxone 1-2 g IV daily for 10-14 days might be effective as an alternate agent.

Follow-Up

• If CSF pleocytosis was present initially, a CSF examination should be repeated every 6 months until the cell count is normal.

• Follow-up CSF examinations also can be used to evaluate changes in the CSF-VDRL or CSF protein after therapy; however, changes in these two parameters occur more slowly than cell counts, and persistent abnormalities might be less important.

• The leukocyte count is a sensitive measure of the effectiveness of therapy. If the cell count has not decreased after 6 months or if the CSF cell count or protein is not normal after 2 years, re-treatment should be considered.

• 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.

• Follow-up for neurosyphilis Among HIV-Infected Persons

• If CSF pleocytosis was present initially, a CSF examination should be repeated every 6 months until the cell count is normal.

• Follow-up CSF examinations also can be used to gauge response after therapy.

• Limited data suggest that changes in CSF parameters may occur more slowly in HIV-infected patients, especially those with more advanced immunosuppression.

• If the cell count has not decreased after 6 months or if the CSF is not normal after 2 years, re-treatment should be considered.