title: Every 36-h gentamicin dosing in neonates with hypoxic-ischemic encephalopathy receiving hypothermia.
abstract: OBJECTIVE
  To examine the impact of a change in the empiric gentamicin dose from 5 mg kg(-1) every 24 h (Q24 h period) to 5 mg kg every 36 h (Q36 h period) on target drug concentration achievement in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia.
  
  
  METHODS
  Gentamicin drug concentrations in neonates with HIE receiving therapeutic hypothermia were examined during two time periods in a retrospective chart review. During the initial treatment period (November 2007 to March 2010; n=29), neonates received Q24 h period. During the second treatment period (January 2011 to May 2012; n=23), the dose was changed to Q36 h period. Cooling criteria and protocol remained the same between treatment periods. Gentamicin drug concentrations including achievement of target trough concentrations (<2 mg l(-1)) were compared between treatment periods. Individual Bayesian estimates of gentamicin clearance were also compared.
  
  
  RESULTS
  Neonates with an elevated trough concentration >2 mg l(-1) decreased from 38 to 4% with implementation of a Q36-h dosing interval (P<0.007). The mean gentamicin trough concentration was 2.0 ± 0.8 mg l(-1) during the Q24 h period and 0.9 ± 0.4 mg l(-1) during the Q36 h period (P<0.001). Peak concentrations were minimally impacted (Q24 h 11.4 ± 2.3 mg l(-1) vs Q36 h 10.0 ± 1.9 mg l(-1); P=0.05). The change in gentamicin trough concentration could not be accounted for by differences in gentamicin clearance between treatment periods (P=0.9).
  
  
  CONCLUSIONS
  A 5 mg kg(-1) every 36-h gentamicin dosing strategy in neonates with HIE receiving therapeutic hypothermia improved achievement of target trough concentration <2 mg l(-1), while still providing high peak concentration exposure.
authors.affiliation: Department of Pediatrics, Stanford University, San Francisco, CA, USA.
authors.forename: A
authors.initials: A
authors.lastname: Frymoyer
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.forename: S L
authors.initials: SL
authors.lastname: Bonifacio
authors.forename: L
authors.initials: L
authors.lastname: Meng
authors.forename: S S
authors.initials: SS
authors.lastname: Lucas
authors.forename: B J
authors.initials: BJ
authors.lastname: Guglielmo
authors.forename: Y
authors.initials: Y
authors.lastname: Sun
authors.forename: D
authors.initials: D
authors.lastname: Verotta
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005260:Female; D005839:Gentamicins / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics*; D005865:Gestational Age; D006801:Humans; D007036:Hypothermia, Induced; D020925:Hypoxia-Ischemia, Brain / Q000628:therapy*; D007231:Infant, Newborn; D008297:Male; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D005839:Gentamicins