What is the recommended treatment for syphilis?

Syphilis Treatment Recommendations

Benzathine penicillin G is the first-line treatment for all stages of syphilis, with dosage varying based on disease stage. 1

Treatment Regimens by Stage

Early Syphilis (Primary, Secondary, Early Latent < 1 year)

• First-line: Benzathine penicillin G 2.4 million units IM in a single dose 1
• Alternative (if penicillin allergic/unavailable):
  • Doxycycline 100 mg orally twice daily for 14 days 1, 2
  • Tetracycline 500 mg orally four times daily for 14 days 1

Late Latent Syphilis or Unknown Duration

• First-line: Benzathine penicillin G 7.2 million units total, administered as 3 doses of 2.4 million units IM at 1-week intervals 1
• Alternative: Doxycycline 100 mg orally twice daily for 28 days 1, 2

Neurosyphilis

• First-line: Penicillin G aqueous 18-24 million units IV daily, administered as 3-4 million units every 4 hours for 10-14 days 1
• Alternative: Ceftriaxone 1 g IV/IM daily for 10 days 2

Special Populations

HIV-Infected Patients

• Same regimens as HIV-negative patients but with closer follow-up 1
• Limited data suggest no benefit to >1 dose of benzathine penicillin G for early syphilis in HIV-infected patients 2

Pregnant Women

• Penicillin is the only proven effective treatment 1
• Desensitization is required if allergic to penicillin 1

Alternative Treatments

Doxycycline

• Acceptable alternative when penicillin cannot be used 2, 3
• Efficacy data shows comparable outcomes to penicillin for early syphilis 3
• May have slightly lower success rates for late latent and undetermined syphilis infections 4

Ceftriaxone

• Reasonable alternative for early syphilis (1 g/day IV/IM for 10 days) 2

Azithromycin

• Not recommended in the United States due to high prevalence of resistance mutations 2, 1
• Despite showing efficacy in some settings 5, concerns about resistance make it unsuitable

Follow-up and Monitoring

• Obtain quantitative non-treponemal test titers (RPR or VDRL) at baseline and follow-up at 6,12, and 24 months 1
• Successful treatment should show a fourfold decline in titers within:
  • 6 months for primary/secondary syphilis
  • 12-24 months for latent/late syphilis 1

Partner Management

• Sexual contacts within 90 days of diagnosis should be treated presumptively, even if seronegative 1
• Contacts from >90 days should be treated presumptively if follow-up is uncertain 1

Common Pitfalls

1. Inadequate follow-up after treatment 1
2. Failure to identify and treat sexual contacts 1
3. Using macrolides empirically despite emerging resistance 1
4. Medication administration issues - BPG is highly viscous and may result in underdosing if not administered properly 6
5. Penicillin shortages - Be aware of potential supply issues that may necessitate alternative treatments 7
6. Misinterpreting treatment failure - Approximately 15% of patients may not meet standard criteria for serological cure 12 months after adequate treatment 1

Benzathine penicillin G remains the gold standard treatment for syphilis across all stages, with specific dosing regimens based on disease stage. Alternative treatments should only be used when penicillin therapy is not feasible.