Treatment of Syphilis in Non-Pregnant Individuals Allergic to Penicillin
For non-pregnant individuals with penicillin allergy, doxycycline 100 mg orally twice daily for 14 days is the recommended alternative treatment for primary and secondary syphilis, while doxycycline 100 mg orally twice daily for 28 days is required for late latent syphilis or syphilis of unknown duration. 1
Treatment Regimens by Stage
Primary and Secondary Syphilis
- Doxycycline 100 mg orally twice daily for 14 days 1, 2
- Alternative: Tetracycline 500 mg orally four times daily for 14 days (less preferred due to compliance issues) 1
Early Latent Syphilis (acquired within preceding year)
- Doxycycline 100 mg orally twice daily for 14 days 1, 2
- Alternative: Tetracycline 500 mg orally four times daily for 14 days 1
Late Latent Syphilis or Syphilis of Unknown Duration
- Doxycycline 100 mg orally twice daily for 28 days 1, 2
- Alternative: Tetracycline 500 mg orally four times daily for 28 days 1
Tertiary Syphilis (non-neurologic)
- Treatment should follow recommendations for late latent syphilis 1
- Doxycycline 100 mg orally twice daily for 28 days 1
Neurosyphilis
- Patients with neurosyphilis who are allergic to penicillin should be desensitized and treated with penicillin if possible 1
- Consultation with an infectious disease specialist is recommended 1
Efficacy of Alternative Regimens
- Clinical studies have demonstrated comparable serological response rates between doxycycline and benzathine penicillin G for early syphilis treatment 3, 4, 5
- A retrospective study found no statistically significant differences in serological response rates at 6 months (69.5% vs. 75.0%) and 12 months (92.4% vs. 96.2%) between doxycycline and penicillin groups 4
- Doxycycline appears to be slightly less effective for late latent and undetermined syphilis infections compared to penicillin 6
Important Considerations
- Doxycycline is preferred over tetracycline due to better compliance with twice-daily dosing versus four-times-daily dosing 1
- Close clinical and serological follow-up is essential for all patients treated with alternative regimens 1
- Erythromycin (500 mg orally four times daily for 14 days) may be considered for patients who cannot tolerate doxycycline or tetracycline, but it is less effective than other regimens 1
- Ceftriaxone has been suggested as an alternative, but optimal dosing is not well established and clinical experience is limited 1
Follow-Up Recommendations
- Quantitative nontreponemal serologic tests should be repeated at 6,12, and 24 months after treatment 1
- Re-treatment should be considered if:
- Titers increase fourfold
- An initially high titer (>1:32) fails to decline at least fourfold within 12-24 months
- Signs or symptoms attributable to syphilis develop 1
Special Situations
- For patients whose compliance with therapy or follow-up cannot be ensured, penicillin desensitization and treatment with penicillin should be considered 1
- HIV-infected patients can be treated with the same doxycycline regimens, but should be monitored more closely (at 3-month intervals instead of 6-month intervals) 1, 7
- The efficacy of alternative regimens in HIV-infected persons has not been well studied 1, 7