What is the antiviral of choice for a patient presenting with viral encephalitis, specifically herpes simplex virus (HSV) or varicella-zoster virus (VZV) infection?

Viral Encephalitis: Antiviral of Choice

Intravenous acyclovir at 10 mg/kg every 8 hours is the antiviral of choice for viral encephalitis, particularly when HSV or VZV is suspected, and should be initiated immediately upon clinical suspicion without waiting for diagnostic confirmation. 1, 2, 3

Immediate Empirical Treatment

• Start IV acyclovir within 6 hours of hospital admission if there is any clinical suspicion of viral encephalitis, even before CSF results or neuroimaging are available 3
• Early treatment (within 4 days of symptom onset) reduces mortality from 28% to 8%, while delaying treatment beyond 48 hours after hospital admission significantly worsens prognosis 2, 4, 3
• Without antiviral treatment, mortality exceeds 70% 3

Standard Dosing Protocols

Adults and Children >12 Years with Normal Renal Function

• Acyclovir 10 mg/kg IV every 8 hours for 14-21 days 1, 2, 4, 3
• The 14-21 day duration is critical; shorter courses are associated with relapse rates up to 5% 3

Neonates

• Acyclovir 20 mg/kg IV every 8 hours for 21 days 1, 4, 3
• This higher dosage regimen has reduced neonatal mortality to 5% 3

Children 3 Months to 12 Years

• Acyclovir 500 mg/m² IV every 8 hours 4

Renal Impairment

• Reduce dose in patients with pre-existing renal impairment, as acyclovir plasma concentrations are higher in these patients 3, 5

Specific Viral Pathogens

Herpes Simplex Virus (HSV-1 and HSV-2)

• Acyclovir is the treatment of choice (Grade A-I recommendation) 1
• Intravenous acyclovir is the accepted standard treatment for herpes simplex encephalitis 6, 7, 8
• Mortality has been reduced to approximately 25% with acyclovir treatment 7

Varicella-Zoster Virus (VZV)

• Acyclovir is recommended (Grade B-III recommendation) 1
• Ganciclovir can be considered as an alternative (Grade C-III) 1
• Adjunctive corticosteroids can be considered (Grade C-III) 1

Diagnostic Workup During Treatment

• Perform HSV PCR on all CSF specimens in patients with encephalitis 1
• If initial HSV PCR is negative but clinical suspicion remains high (compatible clinical syndrome or temporal lobe localization on neuroimaging), repeat PCR 3-7 days later 1, 3
• False-negative PCR results can occur if the sample is taken less than 72 hours after symptom onset 3
• PCR sensitivity is 96-98% in adults but can be as low as 75% in neonates 3

End-of-Treatment Assessment

• Perform repeat lumbar puncture with HSV PCR at 14-21 days after initial treatment completion 4
• If HSV PCR remains positive, this indicates ongoing viral replication requiring continued antiviral therapy 4
• Continue IV acyclovir with weekly PCR monitoring until negative if PCR remains positive 4, 3

Critical Pitfalls to Avoid

Do Not Confuse Meningitis with Encephalitis

• Acyclovir is NOT indicated for aseptic meningitis (HSV or VZV meningitis without encephalitis features) 2
• Encephalitis involves altered mental status, confusion, behavioral changes, seizures, or focal neurological deficits 2
• Unnecessary use of acyclovir for aseptic meningitis can lead to nephropathy, which occurs in up to 20% of patients after 4 days of IV therapy 2, 4

Do Not Stop Treatment Prematurely

• A single negative PCR result should not be used to suspend treatment if clinical suspicion persists 3
• Safe suspension of acyclovir in immunocompetent patients requires ALL of the following: negative HSV PCR (taken >72 hours after symptom onset), normal MRI (performed >72 hours after symptom onset), CSF cell count <5 × 10⁶/L, and normal level of consciousness 3

Monitor for Nephrotoxicity

• Monitor renal function closely during treatment, as acyclovir-induced nephropathy occurs in up to 20% of patients 4
• Ensure adequate hydration to prevent crystalluria and obstructive nephropathy 4

Alternative Agents

Foscarnet

• Consider foscarnet in patients who deteriorate despite acyclovir treatment 3
• Foscarnet is the treatment of choice for acyclovir-resistant HSV strains, which can emerge in immunocompromised patients 5, 7

Valacyclovir

• Valacyclovir (oral prodrug of acyclovir) is NOT appropriate for acute viral encephalitis 9
• It may be considered for B virus encephalitis (Grade B-III) 1

Poor Prognostic Factors

• Age over 30 years 3
• Glasgow Coma Scale score <6 3
• Treatment initiation ≥4 days after symptom onset 4, 3
• Delay in treatment initiation after hospital admission 4, 3

Specialist Involvement

• All decisions regarding corticosteroid use or extended antiviral therapy should involve specialists experienced in managing HSV encephalitis 4
• Consider infectious disease and neurology consultation for complex cases 4