What are the guidelines for treating syphilis?

Guidelines for Syphilis Treatment

Benzathine penicillin G remains the first-line treatment for all stages of syphilis, with dosage varying based on disease stage, and doxycycline is the preferred alternative for penicillin-allergic non-pregnant patients. 1

Treatment Recommendations by Stage

Primary, Secondary, and Early Latent Syphilis

• First-line treatment: Benzathine penicillin G 2.4 million units IM in a single dose 1
• Alternative for penicillin-allergic non-pregnant patients: Doxycycline 100 mg orally twice daily for 14 days 1, 2

Late Latent Syphilis or Latent Syphilis of Unknown Duration

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

Neurosyphilis

• First-line treatment: Penicillin G aqueous 18-24 million units IV daily, administered as 3-4 million units every 4 hours for 10-14 days 1
• Note: For neurosyphilis, there is no adequate alternative to penicillin; penicillin-allergic patients should undergo desensitization 3, 1

Special Populations

Pregnant Women

• Must receive penicillin-based treatment regardless of penicillin allergy status
• Penicillin-allergic pregnant women should undergo desensitization followed by appropriate penicillin treatment 1
• Alternative regimens (doxycycline, tetracycline) are contraindicated in pregnancy 2

Children

• Primary/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
• Children diagnosed with syphilis should have CSF examination to exclude neurosyphilis 3

HIV-Infected Patients

• Same treatment regimens as for HIV-negative patients, but closer follow-up is required 1
• Some experts recommend three doses of benzathine penicillin G regardless of syphilis stage 1
• All patients with syphilis should be tested for HIV 3

Follow-up and Monitoring

Serological Response

• Quantitative nontreponemal tests (VDRL, RPR) should be performed at:
  • 3,6,9,12, and 24 months after treatment 1
• Treatment success is indicated by:
  • Resolution of clinical symptoms
  • Fourfold decrease in nontreponemal test titers within 6 months (primary/secondary) or 12-24 months (latent) 1

Treatment Failure or Reinfection

• Suspect if:
  • Clinical signs/symptoms persist or recur
  • Sustained fourfold increase in nontreponemal test titer
  • High initial titer (≥1:32) fails to decrease fourfold within 12-24 months 1
• Re-treatment consists of three weekly injections of benzathine penicillin G 2.4 million units IM 1

Management of Sex Partners

• Sexual partners exposed within 90 days of diagnosis of primary, secondary, or early latent syphilis should be treated presumptively, even if seronegative 3, 1
• Partners exposed more than 90 days before diagnosis should be treated presumptively if serologic test results are not immediately available or follow-up is uncertain 3
• For patients with syphilis of unknown duration with high nontreponemal titers (≥1:32), partners should be managed as for early syphilis 3

Jarisch-Herxheimer Reaction

• An acute febrile reaction with headache and myalgia that may occur within 24 hours after treatment 3
• Common in early syphilis; antipyretics may be recommended
• May induce early labor or cause fetal distress in pregnant women, but this concern should not delay therapy 3

Clinical Pitfalls and Caveats

1. Penicillin alternatives: While azithromycin has shown efficacy in some studies 4, 5, macrolide-resistant T. pallidum has emerged, limiting its empirical use 6

2. Neurosyphilis evaluation: Patients with neurologic, ophthalmic, or auditory symptoms should undergo CSF examination regardless of syphilis stage 3

3. Serological follow-up: Failure of nontreponemal titers to decline appropriately may indicate treatment failure or reinfection, requiring re-evaluation and possibly re-treatment 1

4. Penicillin allergy management: For pregnant women and patients with neurosyphilis who are allergic to penicillin, desensitization is required rather than using alternative antibiotics 1, 7

5. HIV co-infection: Patients with HIV may have higher rates of neurological complications and treatment failure, requiring more careful follow-up 1