High-dose acyclovir for neonatal herpes has resulted in what outcome across all disease classifications?

• A. Improved neurodevelopmental outcomes
• B. Significant decreases in mortality
• C. Resistance to acyclovir
• D. No improvement in outcomes

Answer: (B)

High-dose intravenous acyclovir improves survival in neonatal herpes across all disease presentations by rapidly suppressing HSV replication, which is critical in newborns where the infection can spread quickly to the CNS or systemically. Historically, mortality was high, especially with disseminated or CNS disease; starting aggressive antiviral therapy reduces viral load, limits progression, and significantly lowers death risk in SEM, CNS, and disseminated cases. The drug’s action—inhibition of viral DNA polymerase after activation by viral thymidine kinase—helps achieve effective CNS and systemic levels, explaining the broad mortality benefit. While survivors may still face neurodevelopmental challenges, particularly with CNS involvement, mortality outcomes have improved overall with this approach. Resistance to acyclovir is rare in neonates and is not the primary driver of the observed mortality reduction.