What is the treatment for syphilis?

Treatment of Syphilis

Penicillin is the treatment of choice for all stages of syphilis, with the specific regimen depending on the stage of infection. 1

Treatment Regimens by Stage

Early Syphilis (Primary, Secondary, and Early Latent)

• First-line treatment: Benzathine penicillin G 2.4 million units IM as a single dose 1
• For HIV-infected patients with early syphilis, the standard single dose of benzathine penicillin G is sufficient; additional doses have not shown clinical benefit 1

Late Latent Syphilis or Latent Syphilis of Unknown Duration

• First-line treatment: Benzathine penicillin G 2.4 million units IM once weekly for three consecutive weeks (total 7.2 million units) 1
• Before treatment, CSF examination should be considered to exclude neurosyphilis, particularly in HIV-infected persons 1

Neurosyphilis

• First-line treatment: Aqueous crystalline penicillin G 18-24 million units daily, administered as 3-4 million units IV every 4 hours or by continuous infusion for 10-14 days 1
• CSF examination should be performed in patients with neurological, ophthalmic, or otic manifestations 1

Tertiary Syphilis

• CSF examination should be performed before treatment to rule out neurosyphilis 1
• If neurosyphilis is excluded, treat with benzathine penicillin G 2.4 million units IM once weekly for three consecutive weeks 1

Alternative Treatments for Penicillin-Allergic Patients (Non-Pregnant)

Early Syphilis

• 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

• Doxycycline 100 mg orally twice daily for 28 days 1, 2

Special Considerations

Pregnant Women

• Penicillin is the only proven effective treatment during pregnancy 1
• Pregnant women with penicillin allergy should undergo desensitization and then receive penicillin 1

HIV-Infected Patients

• Treatment regimens are the same as for HIV-negative patients 1
• Closer follow-up is recommended to detect potential treatment failure or disease progression 1
• CSF examination should be considered in HIV-infected patients with late latent syphilis 1

Follow-Up

• Clinical and serologic evaluation at 3 months and 6 months after treatment 1
• Treatment success is defined as a fourfold decline in nontreponemal test titers within 3-6 months for early syphilis and within 12-24 months for late syphilis 1, 3
• Patients who fail to show this decline should be evaluated for HIV infection, and if reinfection is unlikely, CSF examination should be considered 1

Common Pitfalls and Caveats

1. Jarisch-Herxheimer reaction: An acute febrile reaction with headache and myalgia that may occur within 24 hours after treatment. Patients should be informed about this possibility 1

2. Serofast state: Some patients maintain stable, low nontreponemal titers despite adequate treatment. Limited data suggest additional antibiotic doses do not improve outcomes in these cases 1

3. Azithromycin resistance: Despite some evidence for efficacy, molecular resistance of T. pallidum to macrolides has been reported, making azithromycin an unreliable alternative 1

4. Neurosyphilis diagnosis: No single test can diagnose neurosyphilis in all patients. The diagnosis often requires combinations of reactive serologic tests, CSF abnormalities, and clinical manifestations 1

5. Treatment of partners: Sexual contacts within 90 days of diagnosis of primary, secondary, or early latent syphilis should be treated presumptively even if seronegative 1

Syphilis remains a significant public health concern with increasing incidence in many regions 4. Early diagnosis and appropriate treatment are essential to prevent progression to more severe stages and to reduce transmission.