PMID- 27977557 OWN - NLM STAT- MEDLINE DCOM- 20170626 LR - 20240407 IS - 1532-0987 (Electronic) IS - 0891-3668 (Print) IS - 0891-3668 (Linking) VI - 36 IP - 4 DP - 2017 Apr TI - Safety of High-dose Acyclovir in Infants With Suspected and Confirmed Neonatal Herpes Simplex Virus Infections. PG - 369-373 LID - 10.1097/INF.0000000000001451 [doi] AB - BACKGROUND: Acyclovir is used to treat herpes simplex virus disease in infants. Treatment with high-dose acyclovir, 60 mg/kg/d, is recommended; however, the safety of this dosage has not been assessed in the past 15 years, and this dosage is not currently approved for infants by the US Food and Drug Administration. METHODS: We included infants with neonatal herpes simplex virus disease treated with >/=14 days of intravenous acyclovir starting in the first 120 days of life admitted to 1 of 42 neonatal intensive care units managed by the Pediatrix Medical Group between 2002 and 2012. We determined the frequency and proportion of infants with clinical and laboratory adverse events (AEs) as well as the number and proportion of infant days with laboratory AEs occurring during acyclovir exposure. RESULTS: We identified 89 infants during the study period with 1658 days of acyclovir exposure. Almost all received high-dose acyclovir therapy (79/89, 89%). The most common clinical AEs were hypotension and seizure, both occurring in 9% of infants. Thrombocytopenia was the most common laboratory AE occurring in 25% of infants and on 9% of infant-days. Elevated creatinine occurred in 2% of infants and 0.2% of infant-days and no infants developed renal failure requiring dialysis. Overall, 45% of infants had >/=1 AE. CONCLUSIONS: In this cohort of infants treated during the high-dose acyclovir era, AEs were common but usually not severe. Many of the AEs reported in this cohort may be related to the underlying infection rather than due to acyclovir exposure. FAU - Ericson, Jessica E AU - Ericson JE AD - From the *Duke Clinical Research Institute, Durham, North Carolina; daggerDepartment of Pediatrics, Penn State College of Medicine, Hershey, Pennsylvania; double daggerDepartment of Pediatrics, CHU Sainte Justine, section signDepartment of Pharmacology, University of Montreal, Montreal, Quebec, Canada; paragraph signDepartment of Pediatrics, Duke University, Durham, North Carolina; and ||Pediatrix-Obstetrix Center for Research and Education, Sunrise, Florida. FAU - Gostelow, Martyn AU - Gostelow M FAU - Autmizguine, Julie AU - Autmizguine J FAU - Hornik, Christoph P AU - Hornik CP FAU - Clark, Reese H AU - Clark RH FAU - Benjamin, Daniel K Jr AU - Benjamin DK Jr FAU - Smith, P Brian AU - Smith PB CN - Pediatric Trials Network Executive Committee and Investigators LA - eng GR - K24 HD058735/HD/NICHD NIH HHS/United States GR - R01 HD081044/HD/NICHD NIH HHS/United States GR - R25 HD076475/HD/NICHD NIH HHS/United States GR - UL1 RR024128/RR/NCRR NIH HHS/United States GR - HHSN275201000003I/HD/NICHD NIH HHS/United States GR - UL1 TR001117/TR/NCATS NIH HHS/United States GR - HHSN272201500006C/AI/NIAID NIH HHS/United States GR - R18 FD005292/FD/FDA HHS/United States GR - R21 HD080606/HD/NICHD NIH HHS/United States GR - T32 HD060558/HD/NICHD NIH HHS/United States GR - HHSN275201000003C/AA/NIAAA NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PL - United States TA - Pediatr Infect Dis J JT - The Pediatric infectious disease journal JID - 8701858 RN - 0 (Antiviral Agents) RN - X4HES1O11F (Acyclovir) RN - Neonatal herpes SB - IM MH - Acyclovir/administration & dosage/*adverse effects/therapeutic use MH - Antiviral Agents/administration & dosage/*adverse effects/therapeutic use MH - Female MH - Herpes Simplex/*drug therapy MH - Humans MH - Infant MH - Infant, Newborn MH - Male MH - Pregnancy Complications, Infectious/*drug therapy MH - Retrospective Studies MH - *Simplexvirus MH - Thrombocytopenia PMC - PMC5348260 MID - NIHMS833543 COIS- Conflicts of Interest C.P.H. receives salary support for research from the National Center for Advancing Translational Sciences of the National Institutes of Health (UL1TR001117). D.K.B. receives support from the National Institutes of Health (NIH) (award 2K24HD058735-06, National Center for Advancing Translational Sciences award UL1TR001117, National Institute of Child Health and Human Development contract HHSN275201000003I, and National Institute of Allergy and Infectious Diseases contract HHSN272201500006I); he also receives research support from Cempra Pharmaceuticals (sub-award to HHSO100201300009C) and industry for neonatal and pediatric drug development (www.dcri.duke.edu/research/coi.jsp). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. P.B.S. receives salary support for research from the National Center for Advancing Translational Sciences of the NIH (UL1TR001117), the National Institute of Child Health and Human Development (1R21HD080606-01A1, HHSN275201000003I and 1R01-HD081044-01), and the Food and Drug Administration (1R18-FD005292-01); he also receives research support from Cempra Pharmaceuticals (sub-award to HHS0100201300009C) and industry for neonatal and pediatric drug development (www.dcri.duke.edu/research/coi.jsp). J.E.E receives support from the National Institute of Child Health and Human Development of the National Institutes of Health under award number 5T32HD060558. For the remaining authors, none were declared. EDAT- 2016/12/16 06:00 MHDA- 2017/06/27 06:00 PMCR- 2018/04/01 CRDT- 2016/12/16 06:00 PHST- 2016/12/16 06:00 [pubmed] PHST- 2017/06/27 06:00 [medline] PHST- 2016/12/16 06:00 [entrez] PHST- 2018/04/01 00:00 [pmc-release] AID - 10.1097/INF.0000000000001451 [doi] PST - ppublish SO - Pediatr Infect Dis J. 2017 Apr;36(4):369-373. doi: 10.1097/INF.0000000000001451.