What is the recommended treatment for syphilis?

Treatment of Syphilis

Parenteral penicillin G is the preferred drug for treatment of all stages of syphilis, with the specific preparation, dosage, and duration depending on the stage and clinical manifestations of the disease. 1

First-line Treatment Recommendations

Primary and Secondary Syphilis

• Recommended regimen for adults:
  • Benzathine penicillin G, 2.4 million units IM in a single dose 1

Early Latent Syphilis (less than 1 year duration)

• Same as primary and secondary syphilis:
  • Benzathine penicillin G, 2.4 million units IM in a single dose

Late Latent Syphilis (more than 1 year duration) or Latent Syphilis of Unknown Duration

• Benzathine penicillin G, 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units) 1

Neurosyphilis

• Aqueous crystalline penicillin G, 18-24 million units IV daily (3-4 million units every 4 hours) for 10-14 days 1

Pediatric Dosing

• Benzathine penicillin G, 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose 1

Alternative Regimens for Penicillin-Allergic Non-Pregnant Patients

For patients with documented penicillin allergy (except pregnant women and those with neurosyphilis):

• Doxycycline 100 mg orally twice daily for 14 days (early syphilis) or 28 days (late syphilis) 2, 3
• Tetracycline 500 mg orally four times daily for 14 days (early syphilis) or longer for late syphilis 2, 4

Recent research suggests that while doxycycline is effective, it may have slightly lower success rates compared to penicillin, particularly for late latent or undetermined syphilis infections 3.

Special Considerations

Pregnancy

• Penicillin G is the only documented effective treatment for syphilis during pregnancy 1
• Pregnant women with penicillin allergy should undergo desensitization and then receive penicillin treatment 1, 2

HIV Co-infection

• Treatment recommendations are the same as for HIV-negative individuals
• More careful follow-up is required due to potential for atypical serologic responses 1
• HIV testing should be performed for all patients with syphilis 1

Penicillin Shortage Considerations

• Recent shortages of benzathine penicillin G have been reported 5
• In case of unavailability, alternative regimens may be used for non-pregnant patients without neurosyphilis
• However, every effort should be made to locate and administer BPG, especially for pregnant women 5

Follow-Up and Monitoring

• Quantitative nontreponemal tests (VDRL or RPR) should be performed at:
  • 3,6,9, and 12 months after treatment for primary and secondary syphilis
  • 6,12,18, and 24 months for latent or late syphilis 2
• Treatment success is defined as:
  • Four-fold (2 dilution) decrease in nontreponemal test titers within 6 months for primary/secondary syphilis
  • Four-fold decrease within 12-24 months for latent/late syphilis 2
• Patients with neurosyphilis require serial CSF examinations to ensure adequate treatment 2

Jarisch-Herxheimer Reaction

• An acute febrile reaction with headache, myalgia, and other symptoms that may occur within 24 hours after treatment 1
• More common in early syphilis
• Patients should be informed about this possible reaction
• Antipyretics may be used but have not been proven to prevent the reaction
• In pregnant women, this reaction may induce early labor or cause fetal distress, but this should not delay treatment 1

Management of Sex Partners

• Partners exposed within 90 days preceding diagnosis of primary, secondary, or early latent syphilis should be treated presumptively even if seronegative 1
• Partners exposed >90 days before diagnosis should be treated presumptively if serologic results are not immediately available and follow-up is uncertain 1
• For patients with syphilis of unknown duration but high nontreponemal titers (≥1:32), partners should be managed as for early syphilis 1

Common Pitfalls to Avoid

• Using oral penicillin preparations, which are not appropriate for syphilis treatment 1
• Failing to test for HIV in patients diagnosed with syphilis 1
• Inadequate follow-up of serologic response to treatment
• Not considering neurosyphilis in patients with neurologic, ophthalmic, or otologic symptoms
• Forgetting to warn patients about the Jarisch-Herxheimer reaction
• Inadequate treatment of sexual partners, leading to reinfection

Penicillin remains the cornerstone of syphilis treatment after more than 50 years of clinical experience, with no documented cases of penicillin-resistant T. pallidum 1.