What is the treatment for symptomatic cytomegalovirus (CMV) infection in children?

Treatment for Symptomatic Cytomegalovirus (CMV) Infection in Children

Intravenous ganciclovir is the drug of choice for initial treatment of symptomatic CMV disease in children, administered at 5 mg/kg/dose twice daily for 14-21 days, followed by maintenance therapy. 1

Treatment Algorithm Based on Clinical Presentation

Congenital CMV Infection in Newborns

• First-line therapy: Ganciclovir 4-6 mg/kg IV every 12 hours for 6 weeks 1
  • Higher dose (12 mg/kg/day) leads to substantial decrease in viral load 1
  • Benefits: More rapid resolution of liver enzyme abnormalities and less hearing loss at 6-12 months compared to no treatment 1
  • Common adverse effect: Neutropenia (occurs in approximately two-thirds of infants) 1
    • May require dose modification (48% of cases)
    • May require G-CSF support (7% of cases)
    • Risk of gram-negative sepsis

Disseminated CMV Disease/CMV Retinitis in HIV-Infected Children

• First-line therapy: Ganciclovir 5 mg/kg IV twice daily for 14-21 days, then maintenance therapy 1
• Alternative therapy (for ganciclovir-resistant infections): Foscarnet 60 mg/kg IV every 8 hours for 14-21 days, then maintenance 1
• For sight-threatening disease: Consider combination therapy with ganciclovir and foscarnet 1

Monitoring and Adverse Effects

Ganciclovir/Valganciclovir

• Major toxicity: Myelosuppression (anemia, neutropenia, thrombocytopenia) 1
  • Monitor CBC regularly
  • Dose reduction needed in up to 40% of patients
  • Consider G-CSF for severe neutropenia
• Other toxicities: Renal dysfunction, CNS effects, GI dysfunction, elevated liver enzymes 1
• Resistance monitoring: Consider viral load monitoring, especially with prolonged therapy 2

Foscarnet

• Major toxicity: Renal dysfunction (up to 30% of patients) 1
  • Administer slowly (no faster than 1 mg/kg/minute)
  • Use saline fluid loading to minimize nephrotoxicity
  • Modify dose in patients with renal insufficiency
• Other toxicities: Electrolyte imbalances (Ca, P, Mg, K), seizures, cardiac dysrhythmias 1

Special Considerations for Different Age Groups

Neonates and Infants

• Ganciclovir has been evaluated in phase II and III trials for congenital CMV 1
• Valganciclovir oral solution at 16 mg/kg twice daily provides comparable exposure to IV ganciclovir 6 mg/kg twice daily in infants >7 days to 3 months 3, 4
• Careful consideration of risk/benefit ratio is essential due to potential long-term effects 4

Older Children

• For CMV retinitis in older children who can receive adult dosing, valganciclovir may be considered 1
• Oral valganciclovir has replaced oral ganciclovir due to better bioavailability 1

Important Clinical Pitfalls and Caveats

1. Neutropenia management: Neutropenia is common and can be severe; close monitoring is essential, with dose adjustments or G-CSF as needed 1

2. Drug resistance: Emergence of ganciclovir-resistant CMV strains can occur with long-term therapy 1, 2

   • Consider resistance testing if clinical response is poor or viral load increases during treatment

3. Renal function: Both ganciclovir and foscarnet require dose adjustment in renal impairment 1, 3

   • Monitor renal function regularly during treatment

4. Therapeutic drug monitoring: Consider TDM to optimize dosing due to high inter-individual variability in children 5, 6

   • Target AUC24 between 23-70 μg·h/mL has been associated with viral clearance 6

5. Long-term follow-up: All infants with congenital CMV infection should be followed for at least 2 years to monitor hearing and development 7

By following this treatment algorithm and monitoring for potential adverse effects, clinicians can effectively manage symptomatic CMV infections in children while minimizing treatment-related complications.