Standard-dose versus high-dose acyclovir in children treated empirically for encephalitis: a retrospective cohort study of its use and safety.
BACKGROUND
Intravenous acyclovir is the treatment of choice for herpes simplex virus encephalitis. In 2006, the American Academy of Pediatrics updated its dosing recommendations for children aged 3 months to 12 years to receive high-dose acyclovir (60 mg/kg/day). The association between acyclovir dose and toxicity is unclear.


OBJECTIVE
The purpose of our study was to review our institution's experience with standard- and high-dose acyclovir for the empiric treatment of encephalitis.
This retrospective cohort study included patients aged 1 month to 18 years who received acyclovir as empiric treatment for encephalitis between 2005 and 2009 at a tertiary care children's hospital. We excluded patients with baseline renal impairment and those without serum creatinine measurements prior to and during treatment.


METHODS
The main outcome measure of this study was to compare the occurrence of renal injury or failure between children who received the standard- versus high-dose regimen.


RESULTS
Sixty-one patients were included (n = 32 standard-dose; n = 29 high-dose). There was no statistical difference in change in serum creatinine from baseline between children who received standard- versus high-dose acyclovir (0 vs. 5.1 %; p = 0.79). One child in the standard-dose group and three children in the high-dose group developed renal injury or failure during treatment (3.1 vs. 10.3 %; p = 0.34). Children with renal injury or failure were older, had a longer length of stay, and longer duration of therapy than children without.


CONCLUSIONS
The incidence of renal injury or failure was similar between children who received standard-dose and high-dose acyclovir.
Pharmacy Department, Children's and Women's Health Centre of BC, Room 0B9 4480, Oak St, Vancouver, BC, V6H 3V4, Canada, Jennifer.Kendrick@cw.bc.ca.
Jennifer G
JG
Kendrick
Mary H H
MH
Ensom
Andrew
A
Steer
Colin T
CT
White
Eddie
E
Kwan
Roxane R
RR
Carr
D000212:Acyclovir / Q000008:administration & dosage / Q000009:adverse effects*; D000293:Adolescent; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002648:Child; D002675:Child, Preschool; D018792:Encephalitis, Viral / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D006561:Herpes Simplex / Q000188:drug therapy* / Q000453:epidemiology; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D008297:Male; D051437:Renal Insufficiency / Q000139:chemically induced* / Q000453:epidemiology; D012189:Retrospective Studies; D012307:Risk Factors; D062606:Tertiary Care Centers
D000998:Antiviral Agents; D000212:Acyclovir