Tertiary Syphilis

Tertiary syphilis refers to gummas, cardiovascular syphilis, psychiatric manifestations (e.g., memory loss or personality changes), or late neurosyphilis. Guidelines for all forms of neurosyphilis (e.g., early or late neurosyphilis) are discussed elsewhere in these recommendations (see Neurosyphilis, Ocular Syphilis, and Otosyphilis). Persons with gummas and cardiovascular syphilis who are not allergic to penicillin and have no evidence of neurosyphilis by clinical and CSF examination should be treated with the following regimen.

Recommended Regimen for Tertiary Syphilis Among Adults

Tertiary Syphilis with normal CSF Examination: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals

Other Management Considerations

All persons who have tertiary syphilis should receive a CSF examination before therapy is initiated and have an HIV test. Those persons whose HIV test results are negative should be offered HIV PrEP. Persons with CSF abnormalities should be treated with a neurosyphilis regimen. Certain providers treat all persons who have cardiovascular syphilis with a neurosyphilis regimen. These persons should be managed in consultation with an infectious disease specialist. Limited information is available concerning clinical response and follow-up of persons who have tertiary syphilis.

Management of Sex Partners

See Syphilis, Management of Sex Partners.

Special Considerations

Penicillin Allergy

Any person allergic to penicillin should be treated in consultation with an infectious disease specialist.


Pregnant women who are allergic to penicillin should be desensitized and treated with penicillin G. Skin testing or oral graded penicillin dose challenge might be helpful in identifying women at risk for acute allergic reactions (see Management of Persons Who Have a History of Penicillin Allergy; Syphilis During Pregnancy).

HIV Infection

Persons with HIV infection who have tertiary syphilis should be treated as described for persons without HIV (see Syphilis Among Persons with HIV Infection).