Treatment of 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 of infection. 1
Treatment Regimens by Stage
Primary and Secondary Syphilis
- Benzathine penicillin G, 2.4 million units IM in a single dose 2, 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 2, 1
Early Latent Syphilis
- Benzathine penicillin G, 2.4 million units IM in a single dose (same as primary/secondary) 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
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 1
Alternative Treatments for Penicillin-Allergic Non-Pregnant Patients
- For primary and secondary syphilis: Doxycycline 100 mg orally twice daily for 14 days 1, 3
- For late latent syphilis or syphilis of unknown duration: Doxycycline 100 mg orally twice daily for 28 days 1, 3
- Doxycycline appears to be an effective alternative with comparable serological response rates to penicillin in studies of early syphilis 4
Special Populations
Pregnant Women
- Only penicillin G has documented efficacy for preventing maternal transmission 2, 1
- Pregnant women with penicillin allergy should undergo desensitization and be treated with penicillin 2, 1
HIV-Infected Patients
- Treatment regimens are the same as for non-HIV-infected patients 1
- More frequent monitoring is recommended (at 3-month intervals instead of 6-month intervals) 3
Follow-Up and Monitoring
- Quantitative nontreponemal serologic tests (VDRL or RPR) should be repeated at 6,12, and 24 months after treatment 1
- A 4-fold decline in titer is expected within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1
- CSF examination is recommended if titers increase 4-fold, an initially high titer fails to decline at least 4-fold within appropriate timeframe, or neurological signs/symptoms develop 1
Management of Sex Partners
- Persons exposed to a patient with primary, secondary, or early latent syphilis within the preceding 90 days should be treated presumptively, even if seronegative 2, 1
- Persons exposed >90 days before diagnosis should be treated presumptively if serologic test results are not available immediately and follow-up is uncertain 2
- Long-term sex partners of patients with late syphilis should be evaluated clinically and serologically 2, 1
Important Clinical Considerations
- The Jarisch-Herxheimer reaction (acute febrile reaction with headache, myalgia) may occur within 24 hours after treatment, especially in early syphilis 2
- Patients should be informed about this possible adverse reaction 2
- In pregnant women, the Jarisch-Herxheimer reaction may induce early labor or cause fetal distress, but this concern should not prevent or delay therapy 2
Treatment Failure
- Treatment failure is defined as failure of nontreponemal test titers to decline 4-fold within 6 months after therapy for primary or secondary syphilis 1
- Re-treatment with weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks is recommended 1
- CSF examination should be performed if treatment failure is suspected 2