What is the treatment for neonatal herpes simplex virus (HSV) infection?

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Last updated: May 7, 2025View editorial policy

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From the Guidelines

Neonatal herpes should be treated with high-dose intravenous acyclovir at 20 mg/kg body weight/dose three times daily for 21 days for CNS and disseminated disease and for 14 days for skin, eye, and mouth disease. This treatment approach is based on the recommendations from the CDC, the National Institutes of Health, and the Infectious Diseases Society of America, as outlined in a study published in 2004 1. The use of acyclovir has been shown to reduce morbidity and mortality in neonates with HSV infection.

  • Key considerations in the treatment of neonatal herpes include:
    • The dose and duration of intravenous acyclovir therapy, which should be administered for 21 days for CNS and disseminated disease and for 14 days for skin, eye, and mouth disease 1
    • The importance of not discontinuing acyclovir therapy in neonates with CNS disease unless a repeat CSF HSV DNA PCR assay is negative at day 19-21 of treatment 1
    • The need for close monitoring for neurologic sequelae, which can occur even after successful treatment, particularly in infants with CNS disease 1
  • It is essential to initiate treatment as soon as herpes is suspected, without waiting for test results, to improve outcomes and prevent severe complications.
  • Supportive care, including maintaining hydration, managing seizures if present, and monitoring for complications, is also crucial in the management of neonatal herpes.
  • Parents should be educated about the importance of completing the full treatment course and attending follow-up appointments to monitor for neurological sequelae.

From the FDA Drug Label

Neonatal Herpes Simplex Virus Infection Two hundred and two infants with neonatal herpes simplex infections were randomized to receive either acyclovir 10 mg/kg every 8 hours (n = 107) or vidarabine 30 mg/kg/day (n = 95) for 10 days. Acyclovir for Injection is indicated for the treatment of neonatal herpes infections.

The treatment for neonatal herpes is acyclovir 10 mg/kg every 8 hours for 10 days 2.

  • Indication: Acyclovir for Injection is indicated for the treatment of neonatal herpes infections 2.
  • The dosage of 10 mg/kg every 8 hours has been studied in clinical trials and shown to be effective in treating neonatal herpes simplex virus infection 2.

From the Research

Treatment Options for Neonatal Herpes

  • Neonatal herpes simplex virus infections can be treated with intravenous (IV) administration of acyclovir 3
  • The treatment consists of IV acyclovir at 5 mg/kg every 8 hours for 7 to 14 days for hospitalized patients 3
  • For ambulatory patients, therapy is tailored according to age, with oral acyclovir administered at a dosage of 20 mg/kg every eight hours for children less than 12 years of age 3
  • High-dose acyclovir, 60 mg/kg/d, is recommended for the treatment of neonatal herpes simplex virus infections, although the safety of this dosage has not been assessed in the past 15 years 4

Safety and Efficacy of Acyclovir

  • The safety of high-dose acyclovir for the treatment of neonatal herpes simplex virus disease has been established, with an estimate of therapeutic efficacy also sought 5
  • The most common clinical adverse events associated with high-dose acyclovir are hypotension and seizure, both occurring in 9% of infants 4
  • Thrombocytopenia is the most common laboratory adverse event, occurring in 25% of infants and on 9% of infant-days 4
  • The mortality rate remains high even with treatment, highlighting the need for optimization of treatment and prevention strategies 6

Dosing Practices and Recommendations

  • Acyclovir dosing practices vary across neonatal intensive care units, with dosing meeting population pharmacokinetic (PopPK) recommendations increasing over time for some postmenstrual age groups 7
  • The recommended dosage of acyclovir is 60 mg/kg/d, although dosing different than PopPK recommendations remains common 7
  • More research is needed to clarify optimal dosing strategies in infants with neonatal herpes simplex virus infections 7

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Herpes Simplex Virus in Children.

Current treatment options in neurology, 2002

Research

Neonatal Herpes Simplex Viral Infections and Acyclovir: An Update.

The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG, 2017

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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