Syphilis Treatment Recommendations
Benzathine penicillin G is the recommended treatment for syphilis at all stages, with dosage and duration determined by the stage of infection. 1, 2
Treatment Regimens by Stage
Primary and Secondary Syphilis
- Benzathine penicillin G, 2.4 million units IM in a single dose 1, 2
- For children: Benzathine penicillin G, 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose 3
Early Latent Syphilis (acquired within the preceding year)
- Benzathine penicillin G, 2.4 million units IM in a single dose 1, 3
- Early latent syphilis is defined based on documented seroconversion, fourfold increase in titer, history of symptoms, or having a sex partner with documented early syphilis 1
Late Latent Syphilis or Latent Syphilis of Unknown Duration
- Benzathine penicillin G, 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 1, 4
- If a dose is missed during weekly therapy, an interval of 10-14 days between doses might be acceptable before restarting the sequence 1
Tertiary Syphilis
- Benzathine penicillin G, 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 4, 3
- Patients with symptomatic late syphilis should undergo CSF examination before therapy 4
Neurosyphilis
- Aqueous crystalline penicillin G, 18-24 million units daily, administered as 3-4 million units IV every 4 hours for 10-14 days 2, 4
- CSF examination is recommended for diagnosing neurosyphilis in patients with neurological signs/symptoms 1
Alternative Treatments for Penicillin-Allergic Patients
Non-pregnant Adults
Primary and Secondary Syphilis:
Late Latent Syphilis or Latent Syphilis of Unknown Duration:
Special Populations
- Pregnant Women: Only penicillin G is proven effective for preventing maternal transmission; pregnant women with penicillin allergy should undergo desensitization and be treated with penicillin 4, 3
- HIV-infected Patients: Same treatment regimens as non-HIV-infected patients, but with closer follow-up (every 3 months rather than every 6 months) 1, 2
Follow-Up and Monitoring
- Quantitative nontreponemal serologic tests should be repeated at 6,12, and 24 months 1, 3
- A fourfold decline in titer is expected within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1
- Treatment failure is defined as failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis 1, 3
- If treatment failure is suspected, patients should be re-evaluated for HIV infection and undergo CSF examination 1
Management of Sex Partners
- Persons exposed within 90 days preceding the diagnosis of primary, secondary, or early latent syphilis should be treated presumptively even if seronegative 4, 1
- Persons exposed >90 days before diagnosis should be treated presumptively if serologic test results are not immediately available and follow-up is uncertain 4, 1
- Long-term sex partners of patients with late syphilis should be evaluated clinically and serologically 3
Important Clinical Considerations and Pitfalls
- The Jarisch-Herxheimer reaction is an acute febrile reaction that may occur within 24 hours after treatment, especially in early syphilis 1, 2
- Do not use oral penicillin preparations for syphilis treatment as they are ineffective 1
- Do not rely solely on treponemal test antibody titers to assess treatment response, as they correlate poorly with disease activity 1
- Macrolide resistance in T. pallidum is widespread in the United States, making azithromycin an unsuitable alternative 2
- Serologic tests may decline more slowly in patients who have had previous syphilis infections 2
- CSF examination should be performed in patients with neurologic or ophthalmic signs/symptoms, treatment failure, HIV infection, or high serum nontreponemal titers (≥1:32) 4