title: Therapeutic Drug Monitoring in Neonatal HSV Infection on Continuous Renal Replacement Therapy.
abstract: Optimal acyclovir dosing under continuous renal replacement therapy (CRRT) in neonates is unknown. We monitored serum acyclovir levels and herpes simplex virus 1 (HSV-1) DNA levels in a neonate with disseminated HSV-1 infection and renal failure undergoing CRRT. A full-term, 5-day-old female presented with a 2-day history of lethargy and fever. She developed fulminant hepatitis and was diagnosed with HSV-1 infection by real-time polymerase chain reaction. Acyclovir was initiated at 60 mg/kg/day, which was lowered to 20 mg/kg/day because of development of renal failure. She was placed on continuous hemodialysis. Acyclovir dosing was adjusted according to serum acyclovir levels, and HSV-1 viral load was sequentially monitored. Semiquantification of serum HSV-1 levels was performed by real-time polymerase chain reaction. Acyclovir levels were measured by using liquid chromatography-tandem mass spectrometry. Acyclovir was administered at 20 mg/kg intravenously over 1 hour; peak concentration was 18.9 μg/mL. The half-life of acyclovir was estimated to be 2 to 3 h. Viral load remained high during dosing every 24 hours, with a decline of 0.17 log copies/24 hours. Acyclovir dosing was changed to 20 mg/kg/dose every 8 hours, with an average viral load decline of 0.44 log copies/24 hours. Despite the guideline recommendation of 24-hour redosing, acyclovir was dialyzed at a rate that resulted in suboptimal treatment. Individual therapeutic drug monitoring for acyclovir and dosing adjustment may be required to optimize therapy for patients undergoing CRRT.
authors.affiliation: Divisions of Infectious Diseases, Department of Medical Subspecialties.
authors.forename: Takanori
authors.initials: T
authors.lastname: Funaki
authors.affiliation: Divisions of Infectious Diseases, Department of Medical Subspecialties.
authors.forename: Ippei
authors.initials: I
authors.lastname: Miyata
authors.affiliation: Divisions of Infectious Diseases, Department of Medical Subspecialties.
authors.forename: Kensuke
authors.initials: K
authors.lastname: Shoji
authors.affiliation: Acute and Critical Care, Department of Anesthesia and Intensive Care, and.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Enomoto
authors.affiliation: Transplant Surgery, Transplant Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Seisuke
authors.initials: S
authors.lastname: Sakamoto
authors.affiliation: Transplant Surgery, Transplant Center, National Center for Child Health and Development, Tokyo, Japan.
authors.forename: Mureo
authors.initials: M
authors.lastname: Kasahara
authors.affiliation: Divisions of Infectious Diseases, Department of Medical Subspecialties, miyairi-i@ncchd.go.jp.
authors.forename: Isao
authors.initials: I
authors.lastname: Miyairi
mesh_terms: D058186:Acute Kidney Injury / Q000209:etiology / Q000628:therapy*; D000212:Acyclovir / Q000008:administration & dosage*; D000998:Antiviral Agents / Q000008:administration & dosage; D004279:DNA, Viral / Q000032:analysis*; D004305:Dose-Response Relationship, Drug; D016903:Drug Monitoring / Q000379:methods*; D005260:Female; D017583:Hemodiafiltration / Q000379:methods*; D006561:Herpes Simplex / Q000150:complications / Q000628:therapy*; D006801:Humans; D007231:Infant, Newborn; D011251:Pregnancy Complications, Infectious / Q000628:therapy*; D060888:Real-Time Polymerase Chain Reaction; D018139:Simplexvirus / Q000235:genetics*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D000212:Acyclovir