When should intravenous acyclovir be administered for serious herpesvirus infections?

When to Administer Intravenous Acyclovir

Intravenous acyclovir should be administered for life-threatening or disseminated herpesvirus infections, including herpes simplex encephalitis, neonatal HSV, disseminated HSV or VZV in immunocompromised patients, and any herpesvirus infection requiring hospitalization. 1, 2

Absolute Indications for IV Acyclovir

Herpes Simplex Virus (HSV) Infections

Life-threatening HSV disease:

• Herpes simplex encephalitis requires IV acyclovir 10 mg/kg every 8 hours for at least 21 days 3, 2
• Neonatal HSV infection (any form: skin-eye-mouth, CNS, or disseminated) requires IV acyclovir 10 mg/kg every 8 hours for 10 days minimum 2
• Disseminated HSV with visceral organ involvement (hepatitis, pneumonitis, esophagitis) requires IV acyclovir 5–10 mg/kg every 8 hours 3, 4, 2

Severe mucocutaneous HSV in specific populations:

• Immunocompromised patients with systemic HSV infection should receive IV acyclovir with temporary reduction in immunosuppressive medications 1
• Severe HSV gingivostomatitis requiring hospitalization warrants IV acyclovir 5–10 mg/kg every 8 hours until lesions begin to regress, then switch to oral therapy 4
• Pregnant women with life-threatening maternal HSV disease (disseminated infection, encephalitis) require IV acyclovir despite pregnancy 5

Varicella-Zoster Virus (VZV) Infections

Disseminated or invasive VZV:

• Disseminated herpes zoster (≥3 dermatomes, visceral involvement, or hemorrhagic lesions) requires IV acyclovir 10 mg/kg every 8 hours 1, 3
• Primary VZV infection (chickenpox) in immunocompromised patients requires IV acyclovir 1
• Herpes zoster with CNS complications (encephalitis, meningitis, Guillain-Barré syndrome) requires IV acyclovir 10 mg/kg every 8 hours 3
• Complicated ocular or facial herpes zoster with suspected CNS involvement requires IV acyclovir 3

Immunocompromised patients with VZV:

• Patients on active chemotherapy, organ transplant recipients, or those with severe immunosuppression (HIV with low CD4 count) who develop herpes zoster should receive IV acyclovir 10 mg/kg every 8 hours 3
• B-cell depleting therapies (ocrelizumab, rituximab, ofatumumab) with disseminated or poorly responding VZV may require IV rather than oral therapy 3

Neutropenic or Cellular Immune Defect Patients

Suspected or confirmed cutaneous/disseminated HSV or VZV:

• Febrile neutropenic patients with skin lesions should have IV acyclovir added empirically to their antimicrobial regimen for suspected HSV or VZV 1
• Patients with lymphoma, leukemia, or receiving immunosuppressive drugs (anti-TNF agents, monoclonal antibodies) with unexplained skin lesions should receive empiric IV acyclovir in life-threatening situations 1

Relative Indications and Treatment Escalation

When to Escalate from Oral to IV Therapy

Treatment failure on oral antivirals:

• Lesions that have not begun to resolve within 7–10 days of oral therapy suggest possible resistance or inadequate drug levels, warranting switch to IV acyclovir 3
• Suspected acyclovir-resistant VZV (confirmed by viral culture with susceptibility testing) requires IV foscarnet 40 mg/kg every 8 hours, not IV acyclovir 3

Clinical deterioration:

• Development of new systemic symptoms (fever, altered mental status, respiratory symptoms) during oral therapy requires immediate escalation to IV acyclovir 3
• Multi-dermatomal progression or visceral involvement appearing during oral treatment mandates IV therapy 3

Dosing and Monitoring

Standard IV acyclovir dosing:

• HSV encephalitis: 10 mg/kg every 8 hours for ≥21 days 3, 2
• Neonatal HSV: 10 mg/kg every 8 hours for 10 days minimum 2
• Disseminated HSV/VZV or severe immunocompromised patients: 10 mg/kg every 8 hours for 7–10 days until clinical resolution 3, 2
• Moderate HSV disease: 5 mg/kg every 8 hours may be adequate 4, 2

Critical monitoring parameters:

• Baseline renal function must be obtained before initiating IV acyclovir 3, 2
• Renal function monitoring once or twice weekly during therapy is mandatory, with dose adjustments for creatinine clearance <50 mL/min 3, 2
• Adequate hydration must be maintained to prevent acyclovir crystalluria and nephrotoxicity 3
• Watch for thrombotic thrombocytopenic purpura/hemolytic uremic syndrome in immunocompromised patients receiving high-dose IV acyclovir 3

Treatment Duration and Transition to Oral Therapy

Continue IV acyclovir until:

• Clinical response is achieved (lesions begin to regress, fever resolves, neurologic improvement) 1, 3
• All lesions have completely scabbed for mucocutaneous disease 1, 3
• Minimum treatment duration completed (21 days for encephalitis, 10 days for neonatal HSV, 7–10 days for other indications) 3, 2

Transition to oral therapy:

• Switch to oral acyclovir, valacyclovir, or famciclovir once clinical improvement is documented and the patient can tolerate oral medications 1, 4
• Complete a total treatment duration of 14–21 days for systemic HSV infections 1

Common Pitfalls to Avoid

• Do not delay IV acyclovir in suspected herpes simplex encephalitis—empiric treatment should begin immediately while awaiting diagnostic confirmation 3, 2
• Do not use oral therapy alone for disseminated disease, CNS involvement, or severely immunocompromised patients 3, 4
• Do not discontinue IV acyclovir at exactly 7 days if lesions have not fully crusted or clinical resolution is incomplete 3
• Do not assume oral acyclovir failure means acyclovir resistance—inadequate dosing or delayed initiation may be responsible; confirm resistance with viral culture before switching to foscarnet 3
• Do not forget to reduce or temporarily discontinue immunosuppressive medications in patients with disseminated HSV or VZV when clinically feasible 1, 3