Early infections
The first-choice treatment for uncomplicated syphilis remains a single dose of intramuscular penicillin G or a single dose of oral azithromycin. Doxycycline and tetracycline are alternative choices; however, they cannot be used in pregnant women. Antibiotic resistance has developed to a number of agents, including macrolides, clindamycin, and rifampin. Ceftriaxone, a third-generation cephalosporin antibiotic, may be as effective as penicillin-based treatment.
Late infections
For neurosyphilis due to the poor penetration of penicillin G into the central nervous system, those affected are recommended to be given large doses of intravenous penicillin for a minimum of 10 days. If a person is allergic, ceftriaxone may be used or penicillin desensitization attempted. Other late presentations may be treated with once-weekly intramuscular penicillin G for three weeks. If allergic, as in the case of early disease, doxycycline or tetracycline may be used, but for a longer duration. Treatment at this point will limit further progression, but has only slight effect on damage which has already occurred.
Jarisch-Herxheimer reaction
One of the potential side effects of treatment is the Jarisch-Herxheimer reaction. It frequently starts within one hour and lasts for 24 hours, with symptoms of fever, muscles pains, headache, and tachycardia. It is caused by cytokines released by the immune system in response to lipoproteins released from rupturing syphilis bacteria.