What is the recommended treatment for syphilis?

Treatment for Syphilis

Parenteral penicillin G is the preferred drug for treatment of all stages of syphilis, with the specific preparation, dosage, and duration determined by the stage of infection. 1

First-Line Treatment by Stage

Primary and Secondary Syphilis

• Recommended regimen: Benzathine penicillin G, 2.4 million units IM in a single dose 1
• 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 1

Early Latent Syphilis (acquired within the preceding year)

• Recommended regimen: Same as primary and secondary syphilis - Benzathine penicillin G, 2.4 million units IM in a single dose 1

Late Latent Syphilis or Latent Syphilis of Unknown Duration

• Recommended regimen: Benzathine penicillin G, 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 1

Tertiary Syphilis

• Recommended regimen: Benzathine penicillin G, 7.2 million units total, administered as 3 doses of 2.4 million units IM each at 1-week intervals 1

Neurosyphilis

• Requires CSF examination for diagnosis 1
• Treatment requires regimens that achieve treponemacidal levels in the CSF 1

Alternative Treatments for Penicillin-Allergic Patients

Primary and Secondary Syphilis

• Doxycycline: 100 mg orally twice daily for 14 days 1, 2
• Tetracycline: 500 mg orally four times daily for 14 days (less preferred due to gastrointestinal side effects) 1
• Ceftriaxone: 1 g intravenously or intramuscularly daily for 10 days 1

Late Latent Syphilis or Latent Syphilis of Unknown Duration

• Doxycycline: 100 mg orally twice daily for 28 days 1
• Tetracycline: 500 mg orally four times daily for 28 days 1

Special Populations

HIV-Infected Patients

• Treatment regimens are the same as for non-HIV-infected patients 1, 3
• Limited data suggest no benefit to using more than 1 dose of benzathine penicillin G for early syphilis in HIV-infected patients 1, 3
• CSF examination should be performed before treatment in patients with latent syphilis 1

Pregnant Women

• Only penicillin G is proven effective for preventing maternal transmission 1
• Pregnant women with penicillin allergy should undergo desensitization and be treated with penicillin 1
• Some experts recommend an additional dose of benzathine penicillin 2.4 million units IM one week after the initial dose for pregnant women in the third trimester 1

Follow-Up and Monitoring

• Quantitative nontreponemal serologic tests should be repeated at 6,12, and 24 months 1
• A 4-fold decline in titer is expected within 6 months for primary/secondary syphilis and within 12-24 months for late syphilis 1
• CSF examination is recommended if:
  • Titers increase 4-fold
  • An initially high titer (≥1:32) fails to decline at least 4-fold within 12-24 months
  • Neurological signs or symptoms develop 1

Important Considerations

Jarisch-Herxheimer Reaction

• An acute febrile reaction that may occur within 24 hours after any therapy for syphilis 1, 4
• Occurs in approximately 24% of patients treated for early syphilis 4
• Most common symptoms include myalgias (50.8%), chills (45.8%), weakness (39%), and feverishness (35.6%) 4
• Typically begins within 12 hours of treatment (median onset 4.9 hours) and lasts for a median duration of 12.8 hours 4
• More common in secondary syphilis and in patients without HIV 4
• May induce early labor or cause fetal distress in pregnant women 1

Management of Sex Partners

• Persons exposed to a patient with primary, secondary, or early latent syphilis within the preceding 90 days should be treated presumptively, even if seronegative 1
• Persons exposed more than 90 days before examination should be treated presumptively if serologic test results are not immediately available and follow-up is uncertain 1
• Long-term sex partners of patients with late syphilis should be evaluated clinically and serologically 1

Treatment Failure

• Defined as failure of nontreponemal test titers to decline 4-fold within 6 months after therapy for primary or secondary syphilis 1
• Patients with treatment failure should be reevaluated for HIV infection 1
• CSF examination should be considered to rule out neurosyphilis 1
• Re-treatment typically consists of weekly injections of benzathine penicillin G 2.4 million units IM for 3 weeks 1

Penicillin remains the cornerstone of syphilis treatment due to its proven efficacy over decades of clinical experience 1. While alternative regimens exist for penicillin-allergic patients, they should be used with caution and with appropriate follow-up to ensure treatment success.