Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units

Henry P Foote; Haley Thomassy; Leonardo Baquero; Mina Cayli; Elijah Jacobs; Anish Paladugu; Anisha Roy; Elizabeth Heyward; Reese H Clark; Christoph P Hornik; Daniel K Benjamin; Daniel K Benjamin Jr; Rachel G Greenberg

doi:10.1097/INF.0000000000004459

Acyclovir Dosing Practices Across a Multicenter Cohort of Neonatal Intensive Care Units

Pediatr Infect Dis J. 2024 Jun 26. doi: 10.1097/INF.0000000000004459. Online ahead of print.

Authors

Henry P Foote¹, Haley Thomassy^{1

2}, Leonardo Baquero^{1

2}, Mina Cayli^{1

2}, Elijah Jacobs^{1

2}, Anish Paladugu^{1

2}, Anisha Roy^{1

2}, Elizabeth Heyward¹, Reese H Clark³, Christoph P Hornik^{1

4}, Daniel K Benjamin⁵, Daniel K Benjamin Jr^{1

4}, Rachel G Greenberg^{1

4}

Affiliations

¹ From the Department of Pediatrics, Duke University School of Medicine, Durham, NC.
² High School or College Student Affiliated With the Duke Clinical Research Institute's R25 Summer Training in Academic Research Program.
³ Pediatrix Medical Group, Inc, Sunrise, FL.
⁴ Duke Clinical Research Institute, Durham, NC.
⁵ Department of Economics, Clemson University, Clemson, SC.

PMID: 38920385
DOI: 10.1097/INF.0000000000004459

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.