Management of Herpes Meningitis and Encephalitis

Appropriate Treatment for Herpes Meningitis vs. Encephalitis

The British Infection Association explicitly states there is no evidence supporting the use of oral acyclovir or valaciclovir for herpes meningitis (HSV or VZV) 3, 4
Intravenous acyclovir (10 mg/kg three times daily) is the established treatment for HSV encephalitis, reducing mortality from >70% to <30% 5
For HSV encephalitis, intravenous acyclovir should be continued for 14-21 days 6, 2
A repeat lumbar puncture should be performed at the end of treatment to confirm CSF is negative for HSV by PCR 6, 2
If CSF remains positive for HSV, intravenous acyclovir should continue with weekly PCR until negative 6

Oral acyclovir does not achieve adequate levels in the CSF and is therefore not suitable for treating CNS herpes infections 1, 2
While valaciclovir (the valine ester of acyclovir) has better oral bioavailability and is converted to acyclovir after absorption, its use for herpes meningitis is still not supported by evidence 1, 6

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

Failing to distinguish between viral meningitis (where oral acyclovir is not indicated) and HSV encephalitis (where intravenous acyclovir is essential) can lead to inappropriate treatment 3, 4
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