What is the recommended treatment for syphilis?

Recommended Treatment for Syphilis

The recommended treatment for syphilis is parenteral penicillin G, with the specific preparation, dosage, and duration determined by the stage of infection. 1, 2

Treatment by Stage of Infection

Early Syphilis (Primary, Secondary, and Early Latent)

• For primary and secondary syphilis, benzathine penicillin G, 2.4 million units IM in a single dose is the recommended treatment 1, 2
• Early latent syphilis (acquired within the preceding year) is treated with the same regimen: benzathine penicillin G, 2.4 million units IM in a single dose 1, 2
• 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 Syphilis (Late Latent and Tertiary)

• For 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 is recommended 1, 2
• Tertiary syphilis requires the same regimen: benzathine penicillin G, 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 1, 2
• If a dose is missed during weekly therapy, an interval of 10-14 days between doses might be acceptable before restarting the sequence 1

Neurosyphilis

• For neurosyphilis, aqueous crystalline penicillin G, 18-24 million units per day, administered as 3-4 million units IV every 4 hours or by continuous infusion for 10-14 days is recommended 1, 3
• An alternative regimen is penicillin procaine, 2.4 million units IM once daily, plus probenecid 500 mg orally four times daily, for 10-14 days 3

Alternative Treatments for Penicillin-Allergic Patients

• For penicillin-allergic non-pregnant adults with primary and secondary syphilis, doxycycline 100 mg orally twice daily for 14 days is recommended 1, 2
• For penicillin-allergic non-pregnant adults with late latent syphilis, doxycycline 100 mg orally twice daily for 28 days is recommended 1, 2
• For pregnant women and neurosyphilis patients who are allergic to penicillin, desensitization is necessary as penicillin remains the only proven effective therapy 1, 2, 3

Special Populations

HIV-Infected Patients

• HIV-infected patients should receive the same treatment regimens as non-HIV-infected patients 1, 2
• HIV-infected patients may have atypical serologic responses but generally respond well to standard treatment 1, 3
• More careful follow-up is recommended for HIV-infected patients to detect potential treatment failure or disease progression 3

Pregnant Women

• For pregnant women, parenteral penicillin G is the only therapy with documented efficacy for preventing maternal transmission 1, 2
• Pregnant women with penicillin allergy should undergo desensitization and be treated with penicillin 1, 2

Children

• For children with acquired primary or secondary syphilis, benzathine penicillin G, 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose is recommended 2

Follow-Up and Monitoring

• Quantitative nontreponemal serologic tests should be repeated at regular intervals (3,6,12, and 24 months) 1, 2
• A fourfold decline in titer is expected within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1, 2
• Treatment failure is defined as failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis 1, 2
• 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 1, 2
• Persons exposed >90 days before diagnosis should be treated presumptively if serologic test results are not immediately available and follow-up is uncertain 1

Important Clinical Considerations and Pitfalls

• The Jarisch-Herxheimer reaction is an acute febrile reaction that may occur within 24 hours after any syphilis therapy, especially in early syphilis 1, 3
• 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
• Do not use different testing methods (e.g., switching between VDRL and RPR) when monitoring serologic response, as results cannot be directly compared 1
• Benzathine penicillin G provides prolonged treponemicidal levels in serum for 18-25 days after administration, which exceeds the necessary duration of 7-10 days for effective syphilis treatment 4