Acyclovir for Herpes Encephalitis
Yes, acyclovir is the definitive treatment for herpes encephalitis and should be administered immediately at 10 mg/kg intravenously every 8 hours for 14-21 days in adults with normal renal function. 1, 2
Immediate Initiation
- Start acyclovir empirically without waiting for confirmatory testing when herpes encephalitis is clinically suspected, as early treatment within 4 days of symptom onset reduces mortality from 70% to 8% 3, 2, 4
- Delays of more than 2 days between hospital admission and acyclovir administration are independent predictors of poor outcomes 3, 2
- The drug should be started even if lumbar puncture is delayed or if initial CSF PCR is negative, as PCR can be falsely negative early in illness (<72 hours) 1
Standard Dosing Regimens
Adults and children >3 months:
- 10 mg/kg IV every 8 hours for 14-21 days 1, 2
- Dose adjustment is mandatory in renal impairment based on creatinine clearance 3, 2
Neonates (birth to 3 months):
Treatment Duration and Monitoring
- Minimum treatment duration is 14-21 days for confirmed cases, as the original 10-day regimen led to relapses 1, 5
- Repeat lumbar puncture at 14-21 days to confirm CSF is HSV PCR-negative before discontinuing therapy 1, 3
- If CSF remains PCR-positive, continue acyclovir with weekly PCR testing until negative 1, 2
- Continuing viral replication has been documented in some cases despite treatment, justifying extended therapy 1
When Acyclovir Can Be Stopped
Acyclovir may be discontinued in immunocompetent patients only if: 1
- An alternative diagnosis has been definitively 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 neurological symptom onset WITH unaltered consciousness, normal MRI (performed >72 hours after symptom onset), AND CSF white cell count <5 × 10⁶/L
Critical Safety Considerations
Nephrotoxicity prevention:
- Acyclovir can cause reversible crystalluria and obstructive nephropathy in up to 20% of patients, typically after 4 days of therapy 1
- Maintain adequate hydration and monitor renal function closely 2
- Never use oral acyclovir for acute encephalitis—IV therapy is mandatory as oral formulations do not achieve adequate CSF levels 1, 2
Common pitfall: Do not stop acyclovir based on a single negative CSF PCR if clinical suspicion remains high, as initial PCR can be falsely negative 1, 4
Expected Outcomes
Despite appropriate treatment, outcomes remain suboptimal: 3, 2
- 18-month mortality is 28% in adults
- Approximately 50% of survivors have permanent neurological sequelae at 1 year
- Best outcomes occur in patients <30 years old with higher Glasgow Coma Scores at presentation
FDA-Approved Indication
Acyclovir for injection is FDA-approved specifically for the treatment of herpes simplex encephalitis 6, confirming its role as the standard of care for this life-threatening condition.