What is the recommended dosage of acyclovir (antiviral medication) for the treatment of herpetic encephalitis?

Acyclovir Dosing in Herpetic Encephalitis

For adults with normal renal function, administer acyclovir 10 mg/kg intravenously every 8 hours for 14-21 days; for neonates, use 20 mg/kg intravenously every 8 hours for 21 days. 1

Standard Dosing by Age Group

Adults and Children (>3 months)

• Dose: 10 mg/kg IV every 8 hours 1
• Duration: 14-21 days minimum 1
• Adjust for renal impairment: Required when creatinine clearance is reduced 2

Neonates (Birth to 3 months)

• Dose: 20 mg/kg IV every 8 hours 1
• Duration: 21 days 1
• Rationale: Higher dosing in neonates has decreased mortality to 5% with approximately 40% of survivors developing normally, compared to higher relapse rates (8%) with the lower 10 mg/kg dose 1

Children aged 3 months to 12 years

• Minimum duration: 21 days of acyclovir before considering treatment cessation 1
• Rationale: This age group has the highest relapse risk (26-29%), particularly with treatment duration <14 days 1

Critical Timing Considerations

Early initiation is paramount for reducing mortality and morbidity. 1

• Mortality decreases to 8% when therapy is initiated within 4 days of symptom onset 1
• Delays >2 days between hospital admission and acyclovir administration are independent predictors of poor outcome 1
• Start empiric acyclovir immediately in all suspected cases while awaiting diagnostic confirmation 1

Treatment Completion and Monitoring

Repeat Lumbar Puncture Strategy

• Perform repeat LP at 14-21 days to confirm CSF is HSV PCR-negative 1
• If CSF remains PCR-positive: Continue acyclovir with weekly CSF PCR testing until negative 1
• A negative CSF PCR at end of therapy is associated with better outcomes 1

When to Stop Presumptive Treatment (PCR-negative cases)

Acyclovir can be safely discontinued if: 1

• An alternative diagnosis is established, OR
• HSV PCR negative on two occasions 24-48 hours apart AND MRI (performed >72 hours after symptom onset) is not characteristic for HSV encephalitis, OR
• HSV PCR negative once >72 hours after neurological symptom onset WITH normal consciousness, normal MRI (>72 hours after onset), AND CSF white cell count <5×10⁶/L

Special Populations and Dosing Nuances

Obese Patients

• Use adjusted body weight for dosing calculation in obese patients with normal renal function 3
• Actual body weight may lead to nephrotoxicity or neurotoxicity; ideal body weight may result in subtherapeutic concentrations 3
• For patients <79 kg: Consider minimum dosage of 2550 mg/day (850 mg every 8 hours) when possible, as lower weight patients may have worse outcomes with standard weight-based dosing 4

Renal Impairment

• Mandatory dose adjustment based on creatinine clearance 2
• Half-life increases from 2.5 hours (normal function) to 19.5 hours (anuric patients) 2
• Monitor renal function closely, as reversible nephropathy occurs in up to 20% of patients, typically after 4 days of therapy 1

Augmented Renal Clearance

• Patients may require up to maximum recommended doses to maintain therapeutic concentrations 3

Common Pitfalls to Avoid

Inadequate Treatment Duration

• Never use 10-day courses: Original trials used 10 days, but relapse rates are unacceptably high 1
• Relapse rates as high as 5% in adults and 26-29% in children have been reported with shorter courses 1

Premature Discontinuation

• Do not stop acyclovir based on single negative CSF PCR if obtained <72 hours after symptom onset 1
• CSF PCR can remain positive for 7-10 days even after acyclovir initiation 1

Inadequate Hydration

• Maintain adequate hydration and urine flow to prevent crystalluria and obstructive nephropathy 1, 5
• Monitor mental status for neurotoxicity 5

Outcomes Despite Treatment

Even with appropriate acyclovir therapy, outcomes remain suboptimal: 1, 6

• 18-month mortality: 28% in adults
• Approximately 50% of survivors have permanent sequelae at 1 year
• Predictors of poor outcome include age >30 years, Glasgow Coma Score <6, and delayed treatment initiation

The evidence consistently demonstrates that higher doses in neonates and longer treatment durations across all age groups improve outcomes and reduce relapse rates. 1