Syphilis is treated with antibiotics. Injections of penicillin, either in a single shot or provided over several weeks, usually cure the disease. Certain other antibiotics are effective against syphilis for patients with penicillin allergies. However, penicillin is the only option for pregnant women. A pregnant woman with syphilis who is allergic to penicillin must go through desensitization procedures (a process that reduces or eliminates a sensitivity to certain drugs) so that treatment with penicillin can begin.

Some patients have a reaction to syphilis treatment, especially those with secondary syphilis. Reactions (such as the Jarisch-Herxheimer reaction) often occur within a day after treatment and may feel like a worsening of syphilis symptoms, including fever, aches, headache and flu-like symptoms. The reaction usually passes within a day. Reactions may be the result of a large number of bacteria in the body dying at the same time.

After treatment, syphilis patients should have follow-up screening tests at regular intervals (six and 12 months) or until the nontreponemal tests – the tests that screen for a certain antibody not related to syphilis – come back negative. Pregnant women treated for syphilis should have blood tests for syphilis each month for the remainder of their pregnancy. Women who tested negative for syphilis early in their pregnancy should be retested nearer to delivery if there has been additional risk of exposure to the disease.

People treated for syphilis should abstain from sexual activity until their sores have healed completely, and they are informed by their physician that they are no longer infectious. This may take two to three months.

Sexual partners should be notified of the diagnosis so they may seek medical testing and treatment. Patients diagnosed with primary syphilis should notify all sexual contacts from the previous three months. Those people diagnosed with secondary syphilis should notify all sexual partners from the past year. Sexual activity with these partners should stop until they have been tested and, if tests are positive, treated for the infection. In the United States, physicians must report all cases of syphilis to local health authorities and the Centers for Disease Control and Prevention (CDC).