Clinical question: What is the association between delayed acyclovir therapy and death in neonates with herpes simplex virus (HSV) infection?
Background: Neonatal HSV infection may result in significant morbidity and mortality if untreated. Because symptoms upon presentation may be nonspecific and testing may take several days, clinicians must often decide whether to initiate empiric therapy with acyclovir. However, this may also have consequences related to increased costs of care and the side effects of acyclovir.
Study design: Multicenter retrospective cohort study.
Setting: Forty-one freestanding tertiary-care children’s hospitals.
Synopsis: The Pediatric Health Information System (PHIS) database was used to identify 1,086 infants <28 days of age with a discharge diagnosis of HSV from 2003 to 2009 who received their first dose of intravenous acyclovir within the first seven days of admission. Delayed acyclovir was defined as administration after hospital Day One. Propensity scores and multivariate logistic regression analysis were used to attempt to account for patient (e.g. severity of illness) and hospital confounders. The mortality rate was 9.5% (95% confidence interval [CI]: 6.3%-13.82%) for delayed therapy compared with 6.6% (95% CI: 5.0%-8.5%) for early therapy.
Limitations of this study include the inability to identify all potential patient-level confounders that might have led clinicians to initiate early acyclovir therapy. Although the authors attempted to account for variables that might have defined sicker patients, such as intubation or vasoactive agent infusion, they could not identify patients with just skin, eye, or mouth disease from this database, nor could they identify specific clinical concerns, such as hypothermia. Thus, while the authors conclude that empiric acyclovir is prudent if HSV testing is performed, more specific clinical indications cannot be gleaned from this review.
Bottom line: Delayed initiation of acyclovir increases mortality in neonatal HSV infection.
Citation: Shah SS, Aronson PL, Mohamad Z, Lorch SA. Delayed acyclovir therapy and death among neonates with herpes simplex virus infection. Pediatrics. 2011;128(6):1153-1160.
Reviewed by Pediatric Editor Mark Shen, MD, SFHM, medical director of hospital medicine at Dell Children's Medical Center, Austin, Texas.