WHAT'S KNOWN ON THIS SUBJECT:Neonatal herpes simplex virus (HSV) infection, although uncommon, is associated with significant mortality and neurologic morbidity. Acyclovir therapy reduces mortality rates. The association between the timing of acyclovir treatment initiation and mortality is not known.
WHAT THIS STUDY ADDS:In this multicenter observational study of neonates with HSV infection, delayed initiation of acyclovir therapy was associated with in-hospital death. Our data support the use of empiric acyclovir therapy for neonates undergoing testing for HSV infection. abstract OBJECTIVE: To determine the association of delayed acyclovir therapy with death among neonates with herpes simplex virus (HSV) infection.
METHODS:A multicenter, retrospective, cohort study was conducted between January 1, 2003, and December 31, 2009, with 1086 neonates (age: Յ28 days) with HSV infection from 41 tertiary care children's hospitals. Early acyclovir therapy was defined as initiation of intravenous acyclovir treatment within 1 day after hospital admission, and delayed acyclovir therapy was defined as initiation of treatment Ͼ1 and Յ7 days after hospital admission. Multivariate logistic regression models determined the association between delayed acyclovir therapy and death, with the use of propensity scores for each neonate's likelihood of receiving delayed acyclovir treatment to control for differences in illness severity between groups.
RESULTS:The median age was 10 days. Delayed acyclovir therapy was administered to 262 neonates (24.1%). In most cases (86.2%) of delayed receipt, acyclovir administration occurred on the second or third day of hospitalization. The overall mortality rate was 7.3% (95% confidence interval: 5.8%-9.0%); 9.5% of those who received delayed acyclovir treatment and 6.6% of those who received early acyclovir treatment died. In a multivariate analysis, delayed acyclovir therapy was associated with significantly greater odds of death (adjusted odds ratio: 2.63 [95% confidence interval: 1.36 -5.08]) compared with early acyclovir therapy.
CONCLUSIONS:In this multicenter observational study of neonates with HSV infection, delayed initiation of acyclovir therapy was associated with in-hospital death. Our data support the use of empiric acyclovir therapy for neonates undergoing testing for HSV infection.