Abstract
BACKGROUND: Acyclovir is the first-line therapy for neonatal herpes simplex virus infections. Therapy can mitigate morbidity and mortality but carries a risk for toxicity. We aimed to compare acyclovir dosing in neonatal intensive care units to published recommendations based on population pharmacokinetic (PopPK) analysis. METHODS: We performed a multicenter cohort study of infants in neonatal intensive care units managed by the Pediatrix Medical Group from 1997 to 2020. We included all infants who received acyclovir with complete dosing information. Our primary outcome was the proportion of courses with dosing within 80%-120% of the PopPK recommended daily dose and at the recommended dosing frequency. We compared dosing before and after the publication of the 2014 PopPK recommendations using linear probability modeling. RESULTS: We identified 6862 infants with complete dosing information across 308 centers. Dosing met PopPK recommendations for 41% of treatment courses for infants <30 weeks postmenstrual age (PMA), 71% for infants 30 to <36 weeks PMA and <1% for infants ≥ 36 weeks PMA. Comparison of dosing from 1997 to 2013 with that from 2015 to 2020 showed a significant increase in dosing meeting PopPK recommendations for infants <30 weeks PMA ( P = 0.008) and infants 30 to <36 weeks PMA ( P = 0.02) but not infants ≥ 36 weeks PMA ( P = 0.29). No significant increase in dosing meeting PopPK recommendations was seen for any PMA group when comparison was limited to more recent years (2008-2013 vs. 2015-2020). CONCLUSIONS: Dosing meeting PopPK recommendations increased over time for some PMA groups, but dosing different than PopPK recommendations remains common. More research is needed to clarify optimal dosing strategies in these infants.