What is the recommended treatment for viral encephalitis, particularly when caused by herpes simplex virus (HSV)?

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Last updated: November 28, 2025View editorial policy

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Viral Encephalitis Treatment

Immediately initiate intravenous acyclovir 10 mg/kg every 8 hours in all patients with suspected viral encephalitis, even before diagnostic confirmation, as early treatment reduces mortality from 70% to 8-30%. 1, 2, 3

Immediate Empirical Treatment

  • Start acyclovir within 6 hours of hospital admission for any patient presenting with altered consciousness, confusion, behavioral changes, new seizures, or focal neurological signs suggestive of encephalitis 2, 4
  • Do not delay treatment while awaiting CSF PCR results or MRI findings, as treatment delay beyond 48 hours significantly worsens outcomes 2, 5
  • The standard adult dose is 10 mg/kg intravenously every 8 hours for patients with normal renal function 1, 2
  • For neonates, use higher-dose acyclovir at 20 mg/kg intravenously every 8 hours, which has reduced mortality to 5% with approximately 40% of survivors developing normally 1, 2

Treatment Duration and Monitoring

  • Continue intravenous acyclovir for 14-21 days in confirmed HSV encephalitis 1, 2
  • Repeat lumbar puncture at the end of therapy to confirm CSF is negative for HSV by PCR; if positive, continue antiviral therapy 1, 2
  • Monitor renal function throughout treatment, as acyclovir-induced nephropathy affects up to 20% of patients, typically after 4 days of IV therapy 2, 5
  • Ensure adequate hydration during acyclovir treatment to prevent crystalluria and obstructive nephropathy 2, 5

Dose Adjustments for Special Populations

  • Reduce acyclovir dose in patients with pre-existing renal impairment (creatinine clearance <50 mL/min) to prevent nephrotoxicity 2, 3
  • Geriatric patients require dose reduction due to age-related changes in renal function and higher plasma concentrations 3
  • Immunocompromised patients may require longer courses of therapy (beyond 21 days) and closer monitoring 2, 4

Pathogen-Specific Treatment Considerations

Herpes Simplex Virus (HSV)

  • Acyclovir is the definitive treatment of choice for HSV encephalitis, with mortality at 18 months of 25% compared to 59% with older therapies 1, 3
  • Predictors of poor outcome include age >30 years, Glasgow coma score <6, and symptom duration >4 days before starting acyclovir 1, 2
  • Relapse occurs in approximately 5-8% of cases, particularly when treated with lower doses or shorter durations 1

Varicella-Zoster Virus (VZV)

  • Use intravenous acyclovir 10-15 mg/kg three times daily for VZV encephalitis 5, 4
  • Consider adding corticosteroids if there is evidence of vasculopathy or stroke 5, 4

Cytomegalovirus (CMV)

  • Use combination therapy with ganciclovir (5 mg/kg IV every 12 hours) and foscarnet (60 mg/kg IV every 8 hours or 90 mg/kg IV every 12 hours) for 3 weeks 1, 2, 5
  • This combination has shown improvement or stabilization in 74% of patients with CMV encephalitis 1, 2
  • Monotherapy with either agent alone has poor outcomes and high therapeutic failure rates 1

Epstein-Barr Virus (EBV)

  • Acyclovir has limited benefit for EBV encephalitis and is not routinely recommended 2, 5, 4
  • Consider corticosteroids in selected patients with EBV-associated neurologic complications 2

Critical Pitfalls to Avoid

  • Delaying acyclovir beyond 48 hours after hospital admission is the single most important modifiable factor that worsens outcomes 2, 5
  • Inadequate hydration during acyclovir treatment significantly increases nephropathy risk 2, 5
  • Do not withhold empirical acyclovir while pursuing extensive diagnostic workup for alternative diagnoses 2, 5
  • Do not stop acyclovir at 10-14 days; the full 14-21 day course is essential to prevent relapse 1, 6

Supportive Care Requirements

  • Patients with decreased consciousness require evaluation in intensive care for airway protection, ventilator support, and intracranial pressure management 5, 4
  • Monitor for seizures (occur in 38% of HSV encephalitis cases) and treat appropriately 7
  • Arrange outpatient follow-up and access to rehabilitation services, as cognitive impairment, behavioral changes, and focal neurological deficits are common sequelae 4

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Guideline

Encephalitis Treatment Guidelines

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Management of Viral Encephalopathy

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Guideline

Ensefalit Tedavisi

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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