Empirical IV Acyclovir Dosing for Suspected Viral Encephalitis
For adults and children >12 years, administer intravenous acyclovir 10 mg/kg every 8 hours; for children 3 months to 12 years, use 500 mg/m² every 8 hours, with dose reduction required in patients with pre-existing renal impairment. 1
Age-Based Dosing Algorithm
Adults and Children >12 Years
- 10 mg/kg IV every 8 hours (standard dose for HSV encephalitis) 1
- This dosing reduces mortality from >70% to <30% in HSV encephalitis 1, 2
Children 3 Months to 12 Years
- 500 mg/m² IV every 8 hours 1
- This weight-based dosing (approximately 60 mg/kg/day) achieves similar plasma concentrations to the adult 10 mg/kg dose 3
- The higher dose per kilogram in children accounts for their increased renal clearance 3
Neonates and Infants <3 Months
- Dosing should follow neonatal HSV protocols, typically 20 mg/kg IV every 8 hours for CNS disease 3
- Pharmacokinetics differ significantly in this age group with longer elimination half-life (3.8 hours vs 2.4 hours in older children) 3
Timing of Empirical Treatment
Start acyclovir within 6 hours of admission if CSF/imaging results suggest viral encephalitis or if these results are delayed. 1
- Early treatment is critical—delays beyond 48 hours after hospital admission significantly worsen outcomes 1
- Even if initial CSF microscopy or imaging is normal but clinical suspicion remains high, start acyclovir within 6 hours 1
- Treatment should not be withheld while awaiting PCR confirmation, as HSV encephalitis is the most common treatable viral encephalitis 1, 2
Renal Dose Adjustments
Acyclovir must be dose-adjusted in patients with pre-existing renal impairment, as it is primarily renally excreted (62-91% unchanged in urine). 1, 3
Creatinine Clearance-Based Adjustments:
- CrCl >80 mL/min/1.73m²: Standard dosing, half-life 2.5 hours 3
- CrCl 50-80 mL/min/1.73m²: Reduce dose or extend interval, half-life 3 hours 3
- CrCl 15-50 mL/min/1.73m²: Significant dose reduction required, half-life 3.5 hours 3
- Anuric patients: Dose every 24 hours or after dialysis, half-life 19.5 hours 3
Critical Safety Considerations
Nephrotoxicity Prevention
- Reversible nephropathy from crystalluria occurs in up to 20% of patients, typically after 4 days of therapy 1, 4
- Maintain adequate hydration throughout treatment 1
- Monitor renal function regularly during therapy 1, 5
- Risk factors for renal injury include older age, longer duration of therapy, and longer hospital stay 5
Other Rare Adverse Events
- Hepatitis, bone marrow failure, and encephalopathy can occur but are uncommon 1
Duration of Empirical Treatment
Continue acyclovir for 14-21 days if HSV encephalitis is confirmed. 1, 2
When to Stop Empirical Acyclovir:
- If HSV PCR is negative on two occasions 24-48 hours apart AND MRI is not characteristic for HSV encephalitis 6
- If HSV PCR is negative once >72 hours after symptom onset WITH normal consciousness, normal MRI (performed >72 hours after onset), AND CSF WBC <5×10⁶/L 6
- If an alternative diagnosis is confirmed 6
Confirmation of Treatment Success:
- Repeat lumbar puncture at end of treatment to confirm CSF is HSV PCR-negative 1, 6
- If CSF remains positive, continue acyclovir with weekly PCR until negative 1
- In children 3 months-12 years, give minimum 21 days before repeat LP due to higher relapse rates (26-29%) 1
Common Pitfalls to Avoid
Do not use oral acyclovir or valacyclovir for suspected encephalitis—these agents do not achieve adequate CSF levels and are explicitly not recommended for CNS herpes infections. 6, 4, 7
Do not delay treatment for lumbar puncture in severely ill or deteriorating patients—HSV PCR remains positive for 7-10 days after starting acyclovir, allowing later diagnostic confirmation. 1
Do not use empirical acyclovir indiscriminately for all encephalopathy—this practice is not beneficial and can prematurely halt the diagnostic workup for alternative treatable causes. 1, 4
Do not forget to adjust dosing for renal impairment—failure to do so significantly increases nephrotoxicity risk. 1, 3