A 35-year-old woman with a 2-year history of untreated syphilis now presents with fever, headache, and neck stiffness. CSF analysis shows lymphocytic pleocytosis and elevated protein. RPR and FTA-ABS are positive. What is the drug of choice for neurosyphilis (meningovascular syphilis)?

Explanation

## Treatment of Neurosyphilis (Meningovascular Syphilis) **Key Point:** Aqueous crystalline penicillin G (ACPG) is the only first-line agent for neurosyphilis because it achieves bactericidal CSF concentrations that benzathine penicillin cannot reliably achieve. ### Pathophysiology of Neurosyphilis - T. pallidum crosses the blood–brain barrier early in infection (even in primary syphilis) - Meningovascular syphilis involves inflammation of meninges and cerebral vessels - Adequate CSF penetration is critical for cure ### Dosing Regimen for Neurosyphilis | Parameter | Aqueous Crystalline Penicillin G (ACPG) | |---|---| | **Dose** | 18–24 million units IV daily | | **Route** | Intravenous only | | **Frequency** | Continuous infusion or divided doses (3–4 million units Q4H) | | **Duration** | 10–14 days | | **CSF penetration** | 20–30% of serum level (adequate for T. pallidum) | **High-Yield:** ACPG is given IV because: 1. Achieves high serum and CSF levels 2. Bactericidal against T. pallidum in CNS 3. Benzathine penicillin (IM) does NOT achieve adequate CSF levels ### Why Benzathine Penicillin Is Inadequate for Neurosyphilis - Benzathine penicillin is a repository formulation designed for IM use - Peak serum levels are lower than ACPG - CSF penetration is unpredictable and insufficient - Treatment failures and relapse are well-documented with benzathine penicillin in neurosyphilis **Clinical Pearl:** Patients with neurosyphilis require: - IV penicillin therapy (ACPG preferred) - Lumbar puncture before and after treatment to document CSF sterilization - Close follow-up with repeat CSF analysis at 6 months - Jarisch-Herxheimer reaction is common (fever, headache, myalgia within 24 hours) — pretreatment with acetaminophen or NSAIDs is recommended ### Alternative Regimens (Penicillin-Allergic Patients) | Scenario | Alternative | |---|---| | Non-pregnant, IgE-mediated allergy | Ceftriaxone 2 g IV BD × 10–14 days OR Cefotaxime 2 g IV Q4H × 10–14 days | | Pregnant (any allergy) | Penicillin desensitization + ACPG | **Warning:** Doxycycline does NOT achieve adequate CSF levels and is contraindicated in neurosyphilis, even in allergic patients. Desensitization is preferred. **Mnemonic:** **ACPG for CNS** — Aqueous Crystalline Penicillin G for Central Nervous System syphilis. [cite:Harrison 21e Ch 195; CDC STI Guidelines 2021]