Treatment for Syphilis
Parenteral penicillin G is the preferred drug for treatment of all stages of syphilis, with the specific preparation, dosage, and duration determined by the stage and clinical manifestations of the disease. 1
First-Line Treatment by Stage
Primary and Secondary Syphilis
- Recommended regimen for adults: Benzathine penicillin G, 2.4 million units IM in a single dose 1
- For children: Benzathine penicillin G, 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose 1
Latent Syphilis
- Early latent syphilis (< 1 year duration): Benzathine penicillin G, 2.4 million units IM in a single dose
- Late latent syphilis (> 1 year duration) or latent syphilis of unknown duration: Benzathine penicillin G, 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals 1
Tertiary Syphilis
- Benzathine penicillin G, 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals 1
Neurosyphilis
- Aqueous crystalline penicillin G, 18-24 million units per day, administered as 3-4 million units IV every 4 hours for 10-14 days
Alternative Treatments for Non-Pregnant, Penicillin-Allergic Patients
Primary and Secondary Syphilis
- Doxycycline 100 mg orally twice daily for 14 days, OR
- Tetracycline 500 mg orally four times daily for 14 days 2
Late Latent or Latent Syphilis of Unknown Duration
- Doxycycline 100 mg orally twice daily for 28 days, OR
- Tetracycline 500 mg orally four times daily for 28 days 1
Special Populations
Pregnant Women
- Penicillin G is the only proven effective treatment
- Pregnant women with penicillin allergy should undergo desensitization and then receive penicillin 1
- Some experts recommend an additional dose of benzathine penicillin 2.4 million units IM one week after the initial dose for pregnant women in the third trimester 1
HIV-Infected Patients
- Treatment regimens are the same as for non-HIV-infected patients
- CSF examination is recommended for HIV-infected patients with latent syphilis of any duration 1
- More frequent follow-up is recommended due to potential for treatment failure
Follow-Up Evaluation
Quantitative nontreponemal serologic tests (RPR or VDRL) should be performed at:
- 6,12, and 24 months after treatment for primary and secondary syphilis
- 6,12,24, and 36 months for latent or late syphilis 1
Treatment failure or reinfection should be considered if:
- Clinical signs or symptoms persist or recur
- Sustained fourfold increase in titer
- Initial high titer (≥1:32) fails to decline fourfold within 12-24 months 1
Management of Sex Partners
- Persons exposed within 90 days preceding diagnosis of primary, secondary, or early latent syphilis should be treated presumptively even if seronegative
- 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 Considerations
- The Jarisch-Herxheimer reaction (acute febrile reaction with headache and myalgia) may occur within 24 hours after treatment, particularly in early syphilis 1
- In pregnant women, this reaction may induce early labor or cause fetal distress, but this concern should not delay therapy 1
- Oral penicillin preparations are not appropriate for treating syphilis 1
- Recent reports indicate shortages of benzathine penicillin G in some areas, which may necessitate use of alternative treatments 3
Proper diagnosis, appropriate treatment based on disease stage, and adequate follow-up are essential for successful management of syphilis and prevention of its long-term complications.