What is the recommended treatment regimen for syphilis?

Syphilis Treatment Recommendations

The recommended treatment for syphilis is benzathine penicillin G 2.4 million units IM in a single dose for primary and secondary syphilis, while late latent syphilis requires 7.2 million units total, administered as three doses of 2.4 million units IM at 1-week intervals. 1, 2

Treatment by Stage

Primary and Secondary Syphilis

• Benzathine penicillin G 2.4 million units IM in a single dose is the first-line treatment 3, 1, 2
• For children with acquired primary or secondary syphilis: Benzathine penicillin G 50,000 units/kg IM, up to the adult dose of 2.4 million units in a single dose 3

Early Latent Syphilis

• Benzathine penicillin G 2.4 million units IM in a single dose 1
• 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 1

Late Latent Syphilis or 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, 2
• If a dose is missed during weekly therapy, an interval of 10-14 days between doses might be acceptable before restarting the sequence 1

Neurosyphilis

• Aqueous crystalline penicillin G 18-24 million units daily, administered as 3-4 million units IV every 4 hours for 10-14 days 1, 2
• CSF examination is recommended for diagnosing neurosyphilis in patients with neurological signs/symptoms, tertiary syphilis, or those whose serological titers fail to decline appropriately 1

Alternative Treatments for Penicillin-Allergic Patients

Non-Pregnant Adults

• Primary and secondary syphilis: Doxycycline 100 mg orally twice daily for 14 days 1, 2, 4
• Late latent syphilis: Doxycycline 100 mg orally twice daily for 28 days 1, 2
• Tetracycline 500 mg orally four times daily can be used, though compliance is likely better with doxycycline due to less frequent dosing 2

Pregnant Women and Neurosyphilis Patients

• Penicillin remains the only proven effective therapy for pregnant women and neurosyphilis patients 1, 2
• Patients with penicillin allergy should undergo desensitization rather than using alternative antibiotics 1, 2

Special Populations

HIV Co-infection

• HIV-infected patients should receive the same penicillin regimen as HIV-negative patients 1, 2
• Closer follow-up is recommended for HIV-infected patients (every 3 months rather than every 6 months) 2
• All patients diagnosed with syphilis should be tested for HIV infection 3

Pregnant Women

• Parenteral penicillin G is the only therapy with documented efficacy for preventing maternal transmission 1
• Pregnant women should be treated with penicillin regimens appropriate for their stage of syphilis 5

Follow-Up and Monitoring

• Quantitative nontreponemal serologic tests should be repeated at regular intervals (3,6,12, and 24 months) 1, 5
• A fourfold decline in titer is expected within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1, 5
• Treatment failure is defined as failure of nontreponemal test titers to decline fourfold within 6 months after therapy for primary or secondary syphilis 1, 5
• If treatment failure is suspected, patients should be re-evaluated for HIV infection and undergo CSF examination 1

Management of Sex Partners

• Persons exposed within 90 days preceding the diagnosis of primary, secondary, or early latent syphilis should be treated presumptively even if seronegative 3
• Persons exposed >90 days before diagnosis should be treated presumptively if serologic test results are not immediately available and follow-up is uncertain 3
• For identification of at-risk partners, the time periods before treatment are: 3 months plus duration of symptoms for primary syphilis, 6 months plus duration of symptoms for secondary syphilis, and 1 year for early latent syphilis 3

Important Clinical Considerations

• The Jarisch-Herxheimer reaction is an acute febrile reaction that may occur within 24 hours after any syphilis therapy, especially in early syphilis 1, 2
• Patients should be informed about this possible adverse reaction, which may include fever, headache, and myalgia 1, 2
• Macrolide resistance in T. pallidum is widespread in the United States, making azithromycin an unsuitable alternative 2

Common Pitfalls to Avoid

• Do not use oral penicillin preparations for syphilis treatment as they are ineffective 1
• Do not rely solely on treponemal test antibody titers to assess treatment response, as they correlate poorly with disease activity 1
• Do not use different testing methods (e.g., switching between VDRL and RPR) when monitoring serologic response, as results cannot be directly compared 1
• Do not assume treatment success without proper follow-up serologic testing, as treatment failure can occur with any regimen 3