High Dose

High Dose

Background: Despite recent advances in treatment, the mortality and morbidity rates associated with neonatal herpes simplex virus (HSV) disease are still unacceptable. The effects of high dose (HD) acyclovir were investigated.

Methods: Infants younger than 28 days with virologically confirmed HSV disease were offered participation in the open label trial. The first 16 enrollees received intermediate dose (ID) acyclovir, 45 mg/kg/d. The next 72 enrollees received HD acyclovir, 60 mg/kg/d. The drug was given in 3 divided daily doses for 21 days. The patients were followed up prospectively for the first 4 years of life.

Findings: Neutropenia occurred in 21% of the 29 HD acyclovir recipients with HSV disease localized to the skin, eyes, or mouth (SEM) or CNS. In all affected infants, the absolute neutrophil count (ANC) recovered while treatment was continued at the same dosage or after completion of treatment. The neutropenia appeared to have no adverse consequences. No other adverse events occurred. Patients with dissminated HSV disease given HD acyclovir had a significantly greater survival rate than patients previously given standard dose (SD) acyclovir. However, patients with CNS disease had a survival rate comparable to that of patients given SD treatment. In a Cox proportional hazards regression analysis, HD acyclovir recipients had a significantly higher survival rate overall than patients given SD acyclovir.

Conclusions: A 21 day course of IV acyclovir, 60 mg/kg/d, is effective against neonatal CNS and disseminated HSV disease. Serial ANC values should be monitored throughout the treatment course. If the ANC remains lower than 500/mm for a prolonged period, clinicians should consider reducing the acyclovir dosage or administering granulocyte colony stimulating factors.