Neurosyphilis medical therapy: Difference between revisions
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==Overview== | ==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, [[Syphilis laboratory findings#CSF analysis|CSF laboratory abnormalities]] are common in persons with [[Syphilis pathophysiology#Primary syphilis|early syphilis]], even in the absence of clinical neurological findings. [[uveitis|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== | ==Management of Neurosyphilis== | ||
For patients diagnosed with neurosyphilis including ocular or auditory [[syphilis]] with or without positive [[CSF analysis|CSF results]], [[Penicillin#Benzylpenicillin (penicillin G)|aqueous crystalline penicillin G]] is the treatment of choice.<ref name="cdc2015">http://www.cdc.gov/std/tg2015/syphilis.htm#Neurosyphilis Accessed on September 27, 2016</ref> | For patients diagnosed with neurosyphilis including ocular or auditory [[syphilis]] with or without positive [[CSF analysis|CSF results]], [[Penicillin#Benzylpenicillin (penicillin G)|aqueous crystalline penicillin G]] is the treatment of choice.<ref name="cdc2015">http://www.cdc.gov/std/tg2015/syphilis.htm#Neurosyphilis Accessed on September 27, 2016</ref> | ||
:*The recommended regimen is intravenous | :*The recommended regimen is intravenous administration of penicillin every 4 hours or continuously for 10-14 days. | ||
:*If intravenous administration is not possible, then [[Penicillin G procaine|procaine penicillin]] is an alternative (administered daily with [[probenecid]] for two weeks) | :***Oral antibiotics are not recommended for the treatment of neurosyphilis. | ||
:*To approximate | :** | ||
:***If intravenous administration is not possible, then [[Penicillin G procaine|procaine penicillin]] is an alternative (administered daily with [[probenecid]] for two weeks). | |||
* | :*To approximate for [[Syphilis pathophysiology#Latent syphilis|late latent disease]] and to address concerns about slowly dividing [[Treponema Pallidum|treponemes]], [[Penicillin#Benzylpenicillin (penicillin G)|benzathine penicillin G]] is recommend for 3 weeks after the completion of a 14-day course for neurosyphilis. | ||
:*Intramuscular ceftriaxone for 14 days is also shown to be an alternative effective. | |||
===CDC Recommendations: Pharmacotherapy === | ===CDC Recommendations: Pharmacotherapy === | ||
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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.[1]
- 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.
- The recommended regimen is intravenous administration of penicillin every 4 hours or continuously for 10-14 days.
-
- If intravenous administration is not possible, then procaine penicillin is an alternative (administered daily with probenecid for two weeks).
-
- To approximate for late latent disease and to address concerns about slowly dividing treponemes, benzathine penicillin G is recommend for 3 weeks after the completion of a 14-day course for neurosyphilis.
- Intramuscular ceftriaxone for 14 days is also shown to be an alternative effective.
CDC Recommendations: Pharmacotherapy
Recommended Regimen:
- 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.[2]
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.[2]
If compliance with therapy can be ensured, the following alternative regimen might be considered.[2]
- The duration of the recommended and alternative regimens for neurosyphilis are shorter than the duration of the regimen used for late syphilis in the absence of neurosyphilis. Therefore, benzathine penicillin, 2.4 million units IM once per week for up to 3 weeks, can be considered after completion of these neurosyphilis treatment regimens to provide a comparable total duration of therapy.
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.[3][4]
- 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.[5][6][7]
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.[8][9]
- 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.[9]
- 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.[8][10]
- 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.
References
- ↑ http://www.cdc.gov/std/tg2015/syphilis.htm#Neurosyphilis Accessed on September 27, 2016
- ↑ 2.0 2.1 2.2 "Sexually Transmitted Diseases Treatment Guidelines, 2010". Retrieved 2012-12-19.
- ↑ Hook EW, Baker-Zander SA, Moskovitz BL, Lukehart SA, Handsfield HH (1986) Ceftriaxone therapy for asymptomatic neurosyphilis. Case report and Western blot analysis of serum and cerebrospinal fluid IgG response to therapy. Sex Transm Dis 13 (3 Suppl):185-8. PMID: 3764632
- ↑ Shann S, Wilson J (2003) Treatment of neurosyphilis with ceftriaxone. Sex Transm Infect 79 (5):415-6. PMID: 14573840
- ↑ Dowell ME, Ross PG, Musher DM, Cate TR, Baughn RE (1992) Response of latent syphilis or neurosyphilis to ceftriaxone therapy in persons infected with human immunodeficiency virus. Am J Med 93 (5):481-8. PMID: 1442850
- ↑ Smith NH, Musher DM, Huang DB, Rodriguez PS, Dowell ME, Ace W et al. (2004) Response of HIV-infected patients with asymptomatic syphilis to intensive intramuscular therapy with ceftriaxone or procaine penicillin. Int J STD AIDS 15 (5):328-32. DOI:10.1258/095646204323012823 PMID: 15117503
- ↑ Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2008) Antiretroviral therapy is associated with reduced serologic failure rates for syphilis among HIV-infected patients. Clin Infect Dis 47 (2):258-65. DOI:10.1086/589295 PMID: 18532887
- ↑ 8.0 8.1 Marra CM, Maxwell CL, Tantalo L, Eaton M, Rompalo AM, Raines C et al. (2004) Normalization of cerebrospinal fluid abnormalities after neurosyphilis therapy: does HIV status matter? Clin Infect Dis 38 (7):1001-6. DOI:10.1086/382532 PMID: 15034833
- ↑ 9.0 9.1 Marra CM, Maxwell CL, Tantalo LC, Sahi SK, Lukehart SA (2008) Normalization of serum rapid plasma reagin titer predicts normalization of cerebrospinal fluid and clinical abnormalities after treatment of neurosyphilis. Clin Infect Dis 47 (7):893-9. DOI:10.1086/591534 PMID: 18715154
- ↑ Ghanem KG, Moore RD, Rompalo AM, Erbelding EJ, Zenilman JM, Gebo KA (2008) Neurosyphilis in a clinical cohort of HIV-1-infected patients. AIDS 22 (10):1145-51. DOI:10.1097/QAD.0b013e32830184df PMID: 18525260