What is the recommended dosing for aqueous crystalline penicillin G (Penicillin G) in a patient with suspected neurosyphilis?

Recommended Dosing for Aqueous Crystalline Penicillin G in Neurosyphilis

Administer aqueous crystalline penicillin G 18-24 million units per day intravenously, given as 3-4 million units IV every 4 hours or by continuous infusion, for 10-14 days. 1

Standard Dosing Regimen

• Total daily dose: 18-24 million units per day IV 1, 2
• Administration frequency: 3-4 million units every 4 hours OR continuous infusion 1, 2
• Duration: 10-14 days 1, 2

This regimen applies to all patients with neurosyphilis, including those with:

• Clinical neurologic manifestations (cognitive dysfunction, motor/sensory deficits, cranial nerve palsies, meningitis) 1
• Syphilitic eye disease (uveitis, neuroretinitis, optic neuritis) 1
• Syphilitic auditory disease 1

Alternative Regimen (If IV Access or Compliance Issues)

If compliance with IV therapy can be ensured, an alternative is:

• Procaine penicillin: 2.4 million units IM once daily 1
• PLUS Probenecid: 500 mg orally four times daily 1
• Duration: 10-14 days 1

Critical caveat: Do NOT use procaine penicillin without probenecid, as it does not achieve adequate CSF penicillin levels 1. Additionally, avoid probenecid in patients with sulfa allergies due to cross-reactivity risk 1.

Post-Treatment Consideration

Some specialists recommend following the 10-14 day neurosyphilis regimen with supplemental benzathine penicillin G 2.4 million units IM weekly for 3 weeks to provide comparable total treatment duration to late latent syphilis regimens 1. However, this practice lacks consensus and remains optional 1.

Penicillin Allergy Management

• Preferred approach: Penicillin desensitization followed by standard penicillin regimen 1
• Alternative (limited data): Ceftriaxone 2 g daily IM or IV for 10-14 days 1
• Important warning: Cross-reactivity between ceftriaxone and penicillin exists; use with caution 1

Special Populations

HIV-Infected Patients

Use the same dosing regimen (18-24 million units daily for 10-14 days) 1. HIV-infected patients may have higher rates of neurologic complications and treatment failure, necessitating closer monitoring 1.

Pediatric Patients (After Newborn Period)

• Dose: 200,000-300,000 units/kg/day (administered as 50,000 units/kg every 4-6 hours) 2
• Duration: 10-14 days 2

Critical Follow-Up Requirements

• Repeat CSF examination every 6 months until CSF cell count normalizes 1
• CSF leukocyte count is the most sensitive marker of treatment effectiveness 1
• Consider retreatment if:
  • Cell count has not decreased after 6 months 1
  • CSF cell count or protein not normal after 2 years 1

Common Pitfalls to Avoid

1. Underdosing: Do not use lower doses than 18 million units daily—adequate CSF penetration requires high-dose therapy 3
2. Inadequate duration: Complete the full 10-14 day course even if clinical improvement occurs earlier 1, 2
3. Missing ocular involvement: Always perform CSF examination in patients with syphilitic eye disease, as they require neurosyphilis treatment regardless of CSF results 1
4. Procaine penicillin monotherapy: Never use procaine penicillin without probenecid for neurosyphilis 1

Renal Impairment Adjustments

• Creatinine clearance <10 mL/min/1.73m²: Full loading dose, then half the loading dose every 8-10 hours 2
• Creatinine clearance >10 mL/min/1.73m²: Full loading dose, then half the loading dose every 4-5 hours 2