Syphilis Treatment Guidelines

Primary and Secondary Syphilis

The Centers for Disease Control and Prevention (CDC) recommends benzathine penicillin G 2.4 million units IM as a single dose for adults with primary or secondary syphilis 1, 2, 3
For pediatric patients (≥1 month old), the CDC recommends benzathine penicillin G 50,000 units/kg IM (maximum 2.4 million units) as a single dose 1, 4
Children require CSF examination to exclude neurosyphilis before treatment 1, 4
For penicillin-allergic non-pregnant patients, the CDC recommends doxycycline 100 mg orally twice daily for 14 days as a preferred alternative 1, 4, 5
The CDC advises against using azithromycin due to widespread T. pallidum resistance and documented treatment failures in the United States 1, 4

For early latent syphilis, the CDC recommends benzathine penicillin G 2.4 million units IM as a single dose 2, 6
For late latent syphilis or unknown duration, the CDC recommends benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units) 2, 6, 3
Pediatric dosing for latent syphilis is 50,000 units/kg IM (max 2.4 million units) as a single dose for early latent, and 50,000 units/kg IM (max 2.4 million units) weekly for 3 weeks (total 150,000 units/kg, max 7.2 million units) for late latent/unknown duration 2, 6

The CDC recommends aqueous crystalline penicillin G 18-24 million units per day IV, administered as 3-4 million units every 4 hours (or continuous infusion) for 10-14 days for neurosyphilis 3
Syphilitic eye disease should be treated as neurosyphilis with the same IV penicillin regimen, and managed in collaboration with ophthalmology 3

Clinical and serologic evaluation should be performed at 6 months and 12 months after treatment for early syphilis, and every 3 months for HIV-infected patients 1, 4, 5
Treatment failure is suspected if nontreponemal titers fail to decline fourfold (two dilutions) within 6 months for primary/secondary syphilis, or within 12-24 months for late latent syphilis 3, 5
Retreatment with benzathine penicillin G 2.4 million units IM weekly for 3 weeks is recommended, unless CSF examination indicates neurosyphilis 1, 4

HIV-infected patients should receive the same treatment regimens as HIV-negative patients, with more frequent follow-up (every 3 months) 1, 5
Penicillin-allergic pregnant patients must undergo desensitization, as no alternative antibiotics are acceptable 1, 5
The CDC recommends screening pregnant women for syphilis at the first prenatal visit, third trimester, and at delivery 1