What is the recommended treatment for infants diagnosed with Herpes Simplex Virus (HSV) 1 infection?

Treatment of HSV-1 Infection in Infants

Intravenous acyclovir is the definitive treatment for all HSV-1 infections in infants, with dosing of 20 mg/kg every 8 hours for 14-21 days depending on disease extent. 1, 2, 3

Treatment Regimens by Disease Classification

Neonatal Disease (Birth to 28 Days)

CNS or Disseminated Disease:

• Administer IV acyclovir 20 mg/kg/dose three times daily (every 8 hours) for 21 days 1, 2, 4, 3
• Do not discontinue therapy until repeat CSF HSV DNA PCR is negative at day 19-21 of treatment 1, 2, 4
• This is critical because CNS disease carries the highest risk of neurologic sequelae, and premature discontinuation increases mortality 1, 5

Skin, Eye, and Mouth (SEM) Disease:

• Administer IV acyclovir 20 mg/kg/dose three times daily for 14 days 1, 2, 6, 4
• Monitor for cutaneous recurrences during the first 6 months after treatment, as 2-6% of infants develop neurologic sequelae despite apparently successful treatment 1, 2

Disease Beyond Neonatal Period (>28 Days to 12 Years)

CNS or Disseminated Disease:

• Administer IV acyclovir 10 mg/kg/dose three times daily for 21 days 1

Moderate to Severe Gingivostomatitis:

• Start with IV acyclovir 5-10 mg/kg/dose three times daily 1, 2
• After lesions begin to regress, switch to oral acyclovir and continue until lesions completely heal 1

Mild Gingivostomatitis:

• Oral acyclovir 20 mg/kg/dose (maximum 400 mg/dose) three times daily for 5-10 days 1, 6

Diagnostic Approach

Obtain cultures from multiple sites for suspected neonatal HSV:

• Blood, skin vesicles, mouth/nasopharynx, eyes, urine, and stool/rectum 1, 2
• Positive cultures from any site >48 hours after birth indicates viral replication rather than intrapartum contamination 1
• CSF must be tested for HSV DNA by PCR for any infant with suspected CNS involvement 1, 2

Key diagnostic pitfall:

• 39% of infants with disseminated disease, 32% with CNS disease, and 17% with SEM disease do not have skin vesicles at presentation 5
• Do not wait for vesicles to appear before initiating treatment if HSV is suspected based on clinical presentation 5

Critical Safety Monitoring

Renal Function:

• Acyclovir is primarily excreted by the kidney; dose adjustment based on creatinine clearance is mandatory in renal insufficiency 1, 2, 4
• Administer with adequate hydration to minimize renal toxicity 4
• Monitor creatinine levels; elevated creatinine occurs in 2% of infants but renal failure requiring dialysis is rare 7

Hematologic Monitoring:

• Monitor for neutropenia, which occurs in 46% of infants on long-term therapy but is generally self-limited 2, 4
• Thrombocytopenia occurs in 25% of infants and on 9% of treatment days 7

Other Adverse Events:

• Monitor for phlebitis, nausea, vomiting, and rash 2
• Hypotension and seizures each occur in 9% of infants, though these may be related to underlying infection rather than acyclovir 7

Acyclovir-Resistant HSV

For documented acyclovir-resistant infections:

• Administer IV foscarnet 40 mg/kg/dose three times daily or 60 mg/kg/dose twice daily 1
• Alternative: foscarnet 120 mg/kg/day in 2-3 divided doses until infection resolves 4
• Administer slowly over 2 hours (no faster than 1 mg/kg/minute) with saline fluid loading to minimize renal toxicity 4

Timing and Prognosis

Treatment must be initiated immediately upon clinical suspicion:

• Delaying treatment beyond 24 hours of symptom onset significantly reduces efficacy 4
• The interval between symptom onset and treatment initiation has not improved over the past 20 years, remaining a major barrier to better outcomes 5
• Mortality at 12 months for acyclovir-treated HSV encephalitis is 25% compared to 59% with older therapies 3
• For disseminated disease, mortality is associated with AST elevations ≥10 times upper limit of normal and lethargy at treatment initiation 5

Special Populations

HIV-Infected Infants:

• Use the same IV acyclovir dosing as immunocompetent infants 1, 2
• For symptomatic gingivostomatitis: IV acyclovir 5-10 mg/kg/dose three times daily OR oral acyclovir 20 mg/kg/dose three times daily for 7-14 days 1
• Consider secondary suppressive therapy with oral acyclovir for severe recurrences (>3-6 episodes per year) 1

Immunocompromised Infants:

• Episodes are typically longer and more severe, potentially involving the entire oral cavity or extending across the face 2
• More aggressive antiviral therapy and closer monitoring may be necessary 6