What is the recommended treatment for syphilis?

Recommended Treatment for Syphilis

Benzathine penicillin G is the recommended first-line treatment for all stages of syphilis, with specific dosing regimens based on the stage of infection. 1

Treatment Regimens by Stage

Early Syphilis (Primary, Secondary, and Early Latent)

• Benzathine penicillin G, 2.4 million units IM in a single dose 1, 2
• Early latent syphilis is defined as syphilis acquired within the preceding year based on documented seroconversion, fourfold increase in titer, history of symptoms, or having a sex partner with documented early syphilis 2

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, 3
• This extended regimen ensures adequate treatment for potential systemic involvement in late-stage disease 2

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 3, 1
• Patients with symptomatic late syphilis should undergo CSF examination before therapy initiation 3

Neurosyphilis

• Aqueous crystalline penicillin G 18-24 million units per day, administered as 3-4 million units IV every 4 hours or continuous infusion, for 10-14 days 3, 4
• Alternative regimen (if compliance can be ensured): Procaine penicillin 2.4 million units IM once daily plus probenecid 500 mg orally four times daily for 10-14 days 3

Alternative Treatments for Penicillin-Allergic Patients

Non-pregnant Adults with Primary and Secondary Syphilis

• Doxycycline 100 mg orally twice daily for 14 days 1, 2
• This is the preferred alternative when penicillin cannot be used 3

Non-pregnant Adults with Late Latent Syphilis

• Doxycycline 100 mg orally twice daily for 28 days 1, 2
• The efficacy of alternative regimens in HIV-infected persons has not been well-studied 3

Special Populations

• For pregnant women and neurosyphilis patients, penicillin remains the only proven effective therapy 1, 2
• Pregnant women with penicillin allergy should undergo desensitization and be treated with penicillin 1

Follow-Up and Monitoring

• Quantitative nontreponemal serologic tests (RPR, VDRL) should be repeated at 6,12, and 24 months 1, 2
• A fourfold decline in titer is expected within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1
• Treatment failure is defined as failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis 1
• CSF examination is recommended if titers increase 4-fold, an initially high titer fails to decline at least 4-fold within 12-24 months, or neurological signs or symptoms develop 1

HIV Co-infection Considerations

• HIV-infected patients with early-stage syphilis should receive the same treatment as HIV-negative individuals - a single intramuscular injection of 2.4 million units of benzathine penicillin G 3, 5
• A randomized clinical trial comparing single-dose versus three-dose regimens in HIV-infected patients with early syphilis found no significant difference in treatment outcomes, supporting the standard single-dose recommendation 5
• HIV-infected patients may require more careful follow-up to detect potential treatment failure or disease progression 3

Important Clinical Considerations

• The Jarisch-Herxheimer reaction is an acute febrile reaction that may occur within 24 hours after syphilis therapy, especially in early syphilis 2
• Patients should be informed about this possible adverse reaction, which may include headache, myalgia, and other symptoms 2
• Benzathine penicillin G is slowly absorbed with a median time to peak concentration of 48 hours and maintains therapeutic levels for 18-25 days, which exceeds the necessary duration for effective treatment 6

Common Pitfalls to Avoid

• Do not use oral penicillin preparations for syphilis treatment as they are ineffective 2
• Do not rely solely on treponemal test antibody titers to assess treatment response, as they correlate poorly with disease activity 2
• Do not use different testing methods (e.g., switching between VDRL and RPR) when monitoring serologic response, as results cannot be directly compared 2
• Be aware of potential benzathine penicillin G shortages and have alternative treatment plans ready when necessary 7