title: Therapeutic drug monitoring of continuous-infusion acylovir for disseminated herpes simplex virus infection in a neonate receiving concurrent extracorporeal life support and continuous renal replacement therapy.
abstract: Disseminated herpes simplex virus (HSV) infection in neonates represents a devastating entity that yields high mortality. Acyclovir is the primary antiviral agent used to treat life-threatening HSV infections in neonates; however, even though the agent has reduced morbidity overall from these infections, mortality with disseminated disease remains high. Currently, to our knowledge, no data exist regarding therapeutic drug monitoring of acyclovir in the setting of extracorporeal life support (ECLS) or continuous renal replacement therapy (CRRT) coupled with ECLS. We describe the case of a 14-day-old female with disseminated HSV-1 infection that progressed to fulminant hepatic and renal failure, necessitating the use of ECLS for hemodynamic support and CRRT as a treatment modality for hepatic and renal failure. The standard dosage of acyclovir 20 mg/kg/dose intravenously every 8 hours had been initiated, but after conversion to ECLS and CRRT, the patient's dosage was increased to 30 mg/kg/dose every 8 hours. After a repeat viral load remained unchanged from the initial viral load at 1 × 10(8)  copies/ml, the patient was transitioned from intermittent dosing to a continuous infusion of acyclovir added to the dialysate solution for CRRT at a concentration of 5.5 mg/L. To provide an optimal outcome, dosing was designed to maintain acyclovir plasma concentrations of at least 3 mg/L in order to maintain an acyclovir concentration of at least 1 mg/L in the cerebrospinal fluid. The patient's acyclovir serum concentrations measured at 24 and 72 hours after starting continuous-infusion acyclovir via the dialysate were 8.8 and 5.3 mg/L, respectively, allowing for a continuous serum concentration above 3 mg/L. Unfortunately, before a repeat viral load could be obtained to assess the efficacy of the continuous infusion acyclovir, the patient experienced an intracerebral hemorrhage as a complication related to ECLS after which technological support was withdrawn. This is the first report to describe the pharmacokinetics of continuous-infusion acyclovir in a neonate receiving ECLS with concurrent CRRT. These data suggest that adding acyclovir to the dialysate fluid during CRRT is effective in achieving therapeutic drug concentrations despite the complications of adding ECLS and CRRT circuits to a small patient.
authors.affiliation: St. Christopher's Hospital for Children, Philadelphia, Pennsylvania; Drexel University College of Medicine, Philadelphia, Pennsylvania; Alfred I duPont Hospital for Children, Wilmington, Delaware.
authors.forename: Jeffrey J
authors.initials: JJ
authors.lastname: Cies
authors.forename: Wayne S
authors.initials: WS
authors.lastname: Moore
authors.forename: Kyle
authors.initials: K
authors.lastname: Miller
authors.forename: Christine
authors.initials: C
authors.lastname: Small
authors.forename: Dominick
authors.initials: D
authors.lastname: Carella
authors.forename: Susan
authors.initials: S
authors.lastname: Conley
authors.forename: Jason
authors.initials: J
authors.lastname: Parker
authors.forename: Paul
authors.initials: P
authors.lastname: Shea
authors.forename: Arun
authors.initials: A
authors.lastname: Chopra
mesh_terms: D000212:Acyclovir / Q000008:administration & dosage* / Q000493:pharmacokinetics; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics; D016903:Drug Monitoring / Q000379:methods; D005112:Extracorporeal Circulation; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy*; D006801:Humans; D007231:Infant, Newborn; D017114:Liver Failure, Acute / Q000628:therapy / Q000821:virology; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy*; D051437:Renal Insufficiency / Q000628:therapy / Q000821:virology; D017582:Renal Replacement Therapy / Q000379:methods
chemical_list: D000998:Antiviral Agents; D000212:Acyclovir
keywords: CRRT; ECLS; acyclovir; continuous renal replacement therapy; extracorporeal life support; pediatric; pharmacodynamics; pharmacokinetic