Duration of Acyclovir Treatment for Acute Herpes Encephalitis
Intravenous acyclovir should be continued for 14-21 days in patients with proven HSV encephalitis, with a repeat lumbar puncture performed at the end of treatment to confirm CSF HSV PCR negativity; if the PCR remains positive, continue acyclovir with weekly testing until negative. 1, 2, 3
Standard Treatment Duration
- The minimum treatment duration is 14-21 days for confirmed HSV encephalitis in adults and children over 3 months of age 1, 2, 3
- For neonates, extend treatment to a full 21 days 2, 3
- The 10-day treatment courses used in early trials are now considered inadequate, as relapse has been documented when therapy is stopped prematurely 4
Mandatory End-of-Treatment Monitoring
- Perform a repeat lumbar puncture at 14-21 days to confirm CSF is HSV PCR-negative before discontinuing acyclovir 1, 2, 3
- If CSF PCR remains positive at 14-21 days, continue intravenous acyclovir and repeat CSF PCR testing weekly until it becomes negative 1, 2, 3
- A negative CSF PCR at the end of therapy is associated with better clinical outcomes 3
Dosing Throughout Treatment Course
- Maintain the standard dose of 10 mg/kg IV every 8 hours throughout the entire treatment duration for adults with normal renal function 1, 2, 3, 5
- For neonates, use 20 mg/kg IV every 8 hours for the full 21-day course 2, 3
- Adjust doses in patients with renal impairment based on creatinine clearance to prevent crystalluria and obstructive nephropathy 1, 5
Critical Pitfalls to Avoid
- Never discontinue acyclovir at 10 days, as this outdated regimen has been associated with relapse 4
- Do not stop treatment without confirming PCR-negative CSF, even if the patient appears clinically improved 1, 2, 3
- Never switch to oral acyclovir during the acute treatment phase; IV therapy is mandatory for the entire course 2
- Monitor renal function throughout treatment, as acyclovir-induced nephropathy can affect up to 20% of patients, typically manifesting after 4 days of IV therapy 1
Evidence Supporting Extended Duration
The British Infection Association guidelines explicitly recommend 14-21 days based on clinical trial data showing improved outcomes with longer treatment courses 1. A case report documented relapse in an immunocompetent patient who received only 10 days of acyclovir at the recommended dose, with subsequent brain biopsy confirming acyclovir-sensitive HSV-1, leading to the recommendation for 14-21 day courses 4. The American Academy of Neurology and Infectious Diseases Society of America both support this 14-21 day duration with mandatory CSF PCR confirmation at completion 2, 3.