What is the recommended treatment for an adult patient with late congenital syphilis?

Treatment of Late Congenital Syphilis in Adults

Adults with late congenital syphilis should be treated with benzathine penicillin G 7.2 million units total, administered as three doses of 2.4 million units IM at weekly intervals, following the same regimen used for late latent syphilis. 1, 2

Initial Evaluation

Before initiating treatment, perform a comprehensive assessment to exclude neurosyphilis and tertiary complications:

• Obtain CSF examination if any of the following are present: 1, 2

  • Neurologic signs or symptoms (meningitis, hearing loss, stroke)
  • Ophthalmic manifestations (uveitis, iritis)
  • Evidence of tertiary syphilis (aortitis, gumma)
  • HIV co-infection
  • Nontreponemal titer ≥1:32
  • Treatment failure from prior therapy

• Clinical examination should assess for: 1, 2

  • Cardiovascular involvement (aortitis)
  • Gummatous lesions
  • Ophthalmic disease
  • Neurologic abnormalities

• HIV testing is mandatory for all patients with syphilis 1, 2, 3

Treatment Algorithm

Standard Treatment (Normal CSF)

For adults with late congenital syphilis and normal CSF examination:

• Benzathine penicillin G 2.4 million units IM weekly for 3 consecutive weeks (total 7.2 million units) 1, 2, 4

Neurosyphilis Treatment

If CSF examination reveals neurosyphilis:

• Aqueous crystalline penicillin G 18-24 million units per day IV (administered as 3-4 million units every 4 hours or continuous infusion) for 10-14 days 2, 4

Penicillin Allergy Management

For non-pregnant patients with documented penicillin allergy:

• Doxycycline 100 mg orally twice daily for 28 days 1, 2, 4
• Alternative: Tetracycline 500 mg orally four times daily for 28 days 1, 2

Critical caveat: These alternatives have minimal supporting evidence compared to penicillin 1, 5

For pregnant patients with penicillin allergy:

• Penicillin desensitization is mandatory—no exceptions 2, 4
• Penicillin is the only therapy proven to prevent congenital transmission and treat fetal infection 2, 6
• Alternatives like doxycycline, tetracycline, erythromycin, azithromycin, and ceftriaxone are inadequate in pregnancy 2

Follow-Up Protocol

Serologic monitoring schedule:

• Repeat quantitative nontreponemal tests (RPR or VDRL) at 6,12, and 24 months after treatment 1, 2

Treatment failure indicators requiring re-evaluation and CSF examination: 1, 2

• Fourfold increase in nontreponemal titers
• Initially high titer (≥1:32) fails to decline at least fourfold within 12-24 months
• Development of new signs or symptoms of syphilis

Re-treatment approach:

• Three weekly injections of benzathine penicillin G 2.4 million units IM, unless CSF indicates neurosyphilis 2
• Evaluate for HIV infection if treatment failure occurs 2, 7

Important Clinical Considerations

Missed Doses

• If a dose is missed during weekly therapy, an interval of 10-14 days between doses may be acceptable before restarting the sequence 1, 2, 8
• This is NOT acceptable for pregnant patients—they must repeat the full course of therapy 1

Jarisch-Herxheimer Reaction

• Acute febrile reaction may occur within 24 hours of treatment, especially with early manifestations 2, 4
• Inform patients to expect possible headache, myalgia, fever, and other flu-like symptoms 2, 4
• In pregnant patients during second half of pregnancy, this reaction may precipitate premature labor or fetal distress 2

HIV Co-infection

• Use the same penicillin regimens as for non-HIV-infected patients 2, 4
• Closer follow-up is mandatory to detect treatment failure or disease progression 2, 7
• HIV-infected patients with late latent syphilis and RPR titers ≥1:32 or CD4 counts <350 cells/mm³ may be at increased risk for asymptomatic neurosyphilis 7

Common Pitfalls to Avoid

• Do not use oral penicillin preparations—they are ineffective for syphilis treatment 2
• Do not use azithromycin in the United States due to widespread macrolide resistance and documented treatment failures 2, 8
• Do not switch between different nontreponemal tests (RPR vs VDRL) when monitoring serologic response, as results cannot be directly compared 2
• Do not rely solely on treponemal antibody titers to assess treatment response—they correlate poorly with disease activity 2
• Remember that 15-25% of successfully treated patients remain "serofast" with persistent low titers (<1:8) that do not indicate treatment failure 2