Clinicians evaluating for herpes simplex virus (HSV) in febrile infants must balance detection with overtesting, and there is no universally accepted approach to risk stratification. We aimed to describe variation in diagnostic evaluation and empirical acyclovir treatment of infants aged 0 to 60 days presenting with fever and determine the association between testing and length of stay (LOS).


In this retrospective 44-hospital observational study, we used the Pediatric Health Information System database to identify infants aged ≤60 days evaluated for fever in emergency departments from January 2016 through December 2017. We described hospital-level variation in laboratory testing, including HSV, imaging and other diagnostic evaluations, acyclovir use, and LOS. We assessed the relationship between HSV testing and LOS using generalized linear mixed effects models adjusted for age and illness severity.


In 24 535 encounters for fever, the median HSV testing frequency across hospitals was 35.6% (interquartile range [IQR]: 28.5%–53.5%) for infants aged 0 to 21 days and 12% (IQR: 8.6%–15.7%) for infants aged 22 to 60 days. Among HSV-tested patients, median acyclovir use across hospitals was 79.2% (IQR: 68.1%–89.7%) for those aged 0 to 21 days and 63.6% (IQR: 44.1%–73%) for those aged 22 to 60 days. The prevalence of additional testing varied substantially by hospital and age group. Risk-adjusted LOS for HSV-tested infants was significantly longer than risk-adjusted LOS for those not tested (2.6 vs 1.9 days, P < .001).


Substantial variation exists in diagnostic evaluation and acyclovir use, and infants who received HSV testing had a longer LOS than infants who did not. This variability supports the need for further studies to help clinicians better risk-stratify febrile infants and to guide HSV testing and treatment decisions.

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