What is the recommended antiviral regimen for the treatment of viral meningoencephalitis?

Antiviral Regimens for Viral Meningoencephalitis

For viral meningoencephalitis, the recommended antiviral regimen depends on the specific viral etiology, with intravenous acyclovir being the cornerstone treatment for herpes simplex virus (HSV) and varicella-zoster virus (VZV) encephalitis, while no specific antiviral treatment is recommended for enterovirus encephalitis. 1

HSV Encephalitis Treatment

• Intravenous acyclovir 10 mg/kg every 8 hours (three times daily) for 14-21 days is the established treatment for HSV encephalitis in adults with normal renal function 1, 2
• For children with HSV encephalitis: 10 mg/kg intravenously every 8 hours if aged 3 months-12 years, and 10-15 mg/kg if aged >12 years 1
• Early initiation of acyclovir therapy is critical, as mortality decreases significantly when started promptly 1, 3
• A repeat lumbar puncture should be performed at the end of treatment to confirm CSF is negative for HSV by PCR 2
• If CSF remains positive for HSV, intravenous acyclovir should continue with weekly PCR until negative 2
• Oral acyclovir is not suitable for treating CNS herpes infections as it does not achieve adequate levels in the CSF 2, 4

VZV Encephalitis Treatment

• For VZV encephalitis, intravenous acyclovir 10-15 mg/kg three times daily is recommended for up to 14 days 1
• A higher dose (15 mg/kg) may be considered because VZV is less sensitive to acyclovir than HSV, though most clinicians use the 10 mg/kg dose due to potential renal toxicity 1
• Corticosteroids may be beneficial in VZV encephalitis, particularly if there is a vasculitic component (stroke) 1
• A typical steroid regimen is prednisolone 60-80 mg daily for 3-5 days 1
• No specific treatment is needed for VZV cerebellitis as it is usually self-limiting 1

Enterovirus Encephalitis Treatment

• No specific antiviral treatment is recommended for enterovirus encephalitis 1
• For severe cases, pleconaril (if available) or intravenous immunoglobulin may be considered, though evidence is limited 1
• Pleconaril has shown some efficacy in reducing symptoms of aseptic meningitis but has not been evaluated in trials for enterovirus encephalitis 1

Cytomegalovirus (CMV) Encephalitis Treatment

• For CMV encephalitis, a combination of ganciclovir (5 mg/kg intravenously every 12 hours) and foscarnet (60 mg/kg intravenously every 8 hours or 90 mg/kg every 12 hours) for 3 weeks is recommended 1
• This combination therapy has shown improvement or stabilization in 74% of patients with CMV encephalitis or myelitis 1
• Attempts should be made to decrease immunosuppression whenever possible 1

When to Stop Empiric Acyclovir Treatment

• Acyclovir can be stopped in immunocompetent patients if an alternative diagnosis has been made 2, 3
• Acyclovir can be stopped if HSV PCR in the CSF is negative on two occasions 24-48 hours apart, and MRI is not characteristic for HSV encephalitis 2, 5
• Acyclovir can be stopped if HSV PCR in the CSF is negative once >72 hours after neurological symptom onset, with normal consciousness, normal MRI, and CSF white cell count <5×10^6/L 2, 3

Common Pitfalls to Avoid

• Failing to distinguish between viral meningitis (where acyclovir is not indicated) and HSV encephalitis (where intravenous acyclovir is essential) can lead to inappropriate treatment 2, 3
• Unnecessary use of acyclovir for aseptic meningitis can lead to adverse effects including nephropathy, which occurs in up to 20% of patients after 4 days of IV therapy 2, 5
• Delaying acyclovir treatment in suspected HSV encephalitis significantly increases mortality and morbidity 1, 4
• Assuming that oral antiviral agents are adequate for CNS infections (they are not) 2, 4