Every 36-hour Gentamicin Dosing in Neonates with Hypoxic Ischemic Encephalopathy Receiving Hypothermia

OBJECTIVE: To examine the impact of a change in the empiric gentamicin dose from 5 mg/kg every 24h to 5 mg/kg every 36h on target drug concentration achievement in neonates with hypoxic ischemic encephalopathy (HIE) receiving therapeutic hypothermia. STUDY DESIGN: 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 gentamicin 5 mg/kg every 24h (Q24h period). During the second treatment period (January 2011 to May 2012; n=23), the dose was changed to 5 mg/kg every 36h (Q36h period). Cooling criteria and protocol remained the same between treatment periods. Gentamicin drug concentrations including achievement of target trough concentrations (<2 mg/L) were compared between treatment periods. Individual Bayesian estimates of gentamicin clearance were also compared. RESULT: Neonates with an elevated trough concentration >2 mg/L decreased from 38% to 4% with implementation of a Q36h dosing interval (P<0.007). The mean gentamicin trough concentration was 2.0 ± 0.8 mg/L during the Q24h period and 0.9 ± 0.4 mg/L during the Q36h period (P<0.001). Peak concentrations were minimally impacted (Q24h 11.4 ± 2.3 mg/L vs. Q36h 10.0 ± 1.9 mg/L; 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). CONCLUSION: A 5 mg/kg every 36h gentamicin dosing strategy in neonates with HIE receiving therapeutic hypothermia improved achievement of target trough concentration <2 mg/L while still providing high peak concentration exposure.