What is the recommended dose of acyclovir (antiviral medication) for the treatment of herpes simplex virus (HSV) meningitis?

Acyclovir Dosing for HSV Meningitis

For adults with HSV meningitis, administer acyclovir 10 mg/kg intravenously every 8 hours for 14-21 days, with mandatory dose adjustment for renal impairment. 1

Standard Adult Dosing

• The Infectious Diseases Society of America recommends acyclovir 10 mg/kg IV every 8 hours for 14-21 days in adults with normal renal function. 1
• Treatment duration of 14-21 days is essential to ensure adequate viral suppression and prevent relapse, with mortality decreasing to 8% when treatment begins within 4 days of symptom onset. 1
• Intravenous therapy is mandatory for severe cases requiring hospitalization—oral acyclovir is inadequate for acute viral meningitis. 1

Pediatric Dosing Considerations

• Children aged 3 months to 12 years should receive 500 mg/m² IV every 8 hours, which achieves therapeutic plasma concentrations while minimizing toxicity. 1
• Adolescents >12 years receive the adult dose of 10 mg/kg IV every 8 hours. 1
• Neonates require substantially higher dosing at 20 mg/kg IV every 8 hours for 21 days, which has demonstrated improved outcomes with mortality reduced to 5%. 1, 2

Critical Distinction: Meningitis vs. Encephalitis

• HSV-2 meningitis presents with signs of meningeal irritation and lymphocytic pleocytosis in CSF, whereas encephalitis involves altered mental status, focal neurological deficits, and parenchymal brain involvement requiring more aggressive treatment. 1, 3
• For suspected encephalitis, acyclovir should be started within 6 hours of admission, even if initial CSF or imaging is normal. 1
• The same dosing regimen (10 mg/kg IV q8h) applies to both conditions, but distinguishing between them is crucial for prognostic counseling. 1, 4

Renal Dose Adjustments

• Acyclovir must be dose-adjusted in patients with impaired renal function, as the drug is 62-91% renally excreted. 1
• Monitor creatinine clearance and reduce dose accordingly to prevent crystalluria and obstructive nephropathy. 1
• Maintain adequate hydration throughout treatment to reduce nephrotoxicity risk, which manifests in up to 20% of patients after 4 days of IV therapy. 1

Treatment Response Monitoring

• Obtain a repeat CSF specimen for PCR at the end of therapy in patients without appropriate clinical response. 1
• If PCR remains positive for HSV at treatment completion, continue antiviral therapy. 1
• Relapse of HSV infection occurs in up to 5% of cases after completing acyclovir therapy, necessitating ongoing monitoring. 1

Special Populations

Immunocompromised Patients

• HIV-infected patients with severe HSV disease should receive acyclovir 5 mg/kg IV every 8 hours. 1
• If acyclovir resistance is suspected (persistent lesions despite therapy), switch to foscarnet 40 mg/kg IV every 8 hours. 1, 5
• Immunocompromised patients may require higher doses and longer treatment durations. 1

Recurrent HSV-2 Meningitis (Mollaret's Syndrome)

• Most cases of recurrent lymphocytic meningitis are caused by HSV-2. 3
• For acute recurrent episodes with confirmed meningitis, treat with the same IV acyclovir regimen (10 mg/kg q8h for 14-21 days). 3
• Valacyclovir 500 mg twice daily for suppressive therapy does not prevent recurrent HSV-2 meningitis episodes, based on randomized controlled trial evidence. 3

Common Pitfalls to Avoid

• Do not delay treatment while awaiting diagnostic confirmation—start acyclovir empirically if HSV meningitis is suspected, given the life-threatening nature of untreated disease. 4
• Do not use oral acyclovir for acute meningitis requiring hospitalization. 1
• Do not underdose in neonates—they require double the adult weight-based dose (20 mg/kg vs 10 mg/kg). 1, 2
• Monitor ANC at least twice weekly during treatment, as neutropenia occurs in approximately 21% of patients receiving high-dose therapy. 2

Adverse Effects Monitoring

• Nephrotoxicity is the primary concern, occurring in up to 20% of patients after 4 days of IV therapy. 1
• Monitor renal function throughout treatment with serial creatinine measurements. 1
• Rare adverse events include hepatitis, bone marrow suppression (particularly neutropenia with ANC <1000/mm³), and encephalopathy. 1, 2
• Neutropenia typically recovers during continuation of therapy or after completion without apparent adverse sequelae. 2