Disseminated neonatal herpes simplex virus (HSV) is associated with significant morbidity and mortality therefore prompt adequate treatment with antiviral therapy is of great importance. There is little pharmacokinetic/pharmacodynamic data available to guide acyclovir dosing recommendations for neonates maintained on continuous veno-venous hemodiafiltration (CVVHDF) and extracorporeal membrane oxygenation (ECMO).
This report follows the course of two full-term, previously healthy male neonates who were treated with acyclovir for disseminated HSV infection at about 1 week of age. Both were placed on CVVHDF and one on ECMO for their progressive illness. We measured serum acyclovir concentrations and HSV inhibitory concentrations (IC) to ensure adequate dosing when receiving these therapies.
Intravenous acyclovir was given to both neonates at the recommended dose of 20mg/kg/dose. The dosing frequency in the neonate receiving ECMO and CVVHDF was every 8 hours and in the neonate receiving CVVHDF alone was every 12 hours. Acyclovir serum peak and trough concentrations were drawn to assess the efficacy and safety during CVVHDF and ECMO treatment. HSV ICs were measured to assess resistance to acyclovir.
The HSV2 IC for the neonate receiving ECMO and CVVHDF was 3 mcg/mL with serum peak concentration 23 mcg/mL and trough concentration 17 mcg/mL. The HSV1 IC for the neonate receiving CVVHDF was <0.25 mcg/mL with serum peak concentration 31 mcg/mL and trough concentration 15 mcg/mL. Assuming acyclovir levels in the CSF are 30-50% of serum levels the desired minimum serum levels were 10 mcg/mL and 0.83 mcg/L, respectively. Minimum serum trough concentrations were achieved and serum peak concentrations did not exceed the safety threshold of 50 mcg/mL. Both infants died as a result of their profound illness, despite early initiation of acyclovir and adequate serum concentrations.
Optimal acyclovir serum concentrations can be achieved in the presence of CVVHDF and ECMO with 20 mg/kg/dose at intervals of every 8 and every 12 hours for the treatment disseminated neonatal HSV1/2 with variable resistance.
S. Casey, None
K. Pillutla, None
C. Ragsdale, None
M. Fernandez, None
S. Hauger, None