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

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 20mg/kg/dose intravenously every 8hours had been initiated, but after conversion to ECLS and CRRT, the patient's dosage was increased to 30mg/kg/dose every 8hours. After a repeat viral load remained unchanged from the initial viral load at 1x10(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 5.5mg/L. To provide an optimal outcome, dosing was designed to maintain acyclovir plasma concentrations of at least 3mg/L in order to maintain an acyclovir concentration of at least 1mg/L in the cerebrospinal fluid. The patient's acyclovir serum concentrations measured at 24 and 72hours after starting continuous-infusion acyclovir via the dialysate were 8.8 and 5.3mg/L, respectively, allowing for a continuous serum concentration above 3mg/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patient experienced an intracerebral hemorrhage as a complication related to ECLS after which technological support was withdrawn.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.