For herpetic encephalopathy, is IV acyclovir preferred over oral acyclovir?

Treatment of Herpetic Encephalopathy

Intravenous (IV) acyclovir is strongly recommended over oral acyclovir for the treatment of herpetic encephalopathy due to its superior CNS penetration and established efficacy in reducing mortality and morbidity. 1, 2, 3

Rationale for IV Administration

• Oral acyclovir has poor bioavailability (~20%) and inadequate CNS penetration for treating encephalitis 4
• IV acyclovir achieves therapeutic concentrations in the CNS required to treat encephalitis
• Mortality rates for untreated herpetic encephalitis reach 70%, while proper IV treatment reduces mortality to 20-30% 2, 4
• Delayed treatment significantly worsens outcomes, making immediate IV therapy critical

Recommended Dosing Regimen

• Adults and children >12 years: 10 mg/kg IV every 8 hours 2, 3
• Children 3 months-12 years: 500 mg/m² IV every 8 hours 2
• Neonates: 20 mg/kg IV every 8 hours 2
• Duration: 14-21 days for confirmed cases 1, 2

Dose Adjustments

• Renal impairment requires dose adjustment based on creatinine clearance 3:
  • CrCl >80 mL/min: Standard dose
  • CrCl 50-80 mL/min: Standard dose with increased interval
  • CrCl 15-50 mL/min: Reduced dose and increased interval
  • CrCl <15 mL/min: Significantly reduced dose and extended interval

Treatment Initiation and Monitoring

• Begin IV acyclovir immediately upon suspicion of herpetic encephalopathy, without waiting for diagnostic confirmation 2
• Perform lumbar puncture for CSF analysis including HSV PCR, but do not delay treatment if LP is delayed 1, 2
• Monitor renal function regularly, especially after 4 days of therapy when risk of nephropathy increases 1, 2
• Ensure adequate hydration to prevent crystalluria 2

When to Discontinue Treatment

Acyclovir can be stopped in immunocompetent patients if:

• An alternative diagnosis has been made, or
• HSV PCR in CSF is negative on two occasions 24-48 hours apart and MRI is not characteristic for HSV encephalitis, or
• HSV PCR in CSF is negative once >72 hours after symptom onset, with unaltered consciousness, normal MRI, and CSF white cell count <5 × 10^6/L 1, 2

Common Pitfalls to Avoid

1. Using oral acyclovir: Oral acyclovir is inadequate for treating encephalitis due to poor CNS penetration 4, 5
2. Delaying treatment: Starting treatment >4 days after symptom onset significantly worsens outcomes 2
3. Inadequate dosing: Underdosing, particularly in obese patients, may lead to treatment failure 6, 7
4. Stopping treatment too early: A minimum of 14 days is required for confirmed cases 1, 2
5. Ignoring renal function: Failure to adjust doses based on renal function can lead to nephrotoxicity 3

Special Considerations

• For low-weight patients (<79 kg), a minimum dosage of 2550 mg/day (850 mg every 8 hours) is recommended when possible 6
• In obese patients, consider using adjusted body weight rather than actual body weight for dose calculations 7
• A repeat lumbar puncture with HSV PCR testing should be performed at the end of treatment to confirm resolution of infection 2

In summary, IV acyclovir is the only appropriate treatment for herpetic encephalopathy, with oral acyclovir being inadequate due to poor bioavailability and CNS penetration.