During the Emergency Department Evaluation of a Well-Appearing Neonate with Fever, Should Empiric Acyclovir Be Initiated?

Neonatal HSV infection carries significant morbidity and mortality if left untreated. High-quality clinical evidence on when to evaluate and treat for possible HSV infection is lacking. Based on available research, HSV infection in the febrile neonate should be strongly considered if age is < 21 days, or if presenting with concerning clinical features. If testing is performed, empiric treatment with high-dose acyclovir should be initiated. Additional research is needed to further clarify which cases mandate evaluation and treatment for HSV, and to better define treatment protocols.