88: Extended Interval Dosing of Gentamicin in Premature Neonates <32 Weeks Gestational Age and >7 Days of Age

Abstract

Background: Extended interval dosing (EID) of gentamicin results in higher peak and lower trough levels with greater efficacy and reduced toxicity. The clearance, serum half-life and volume of distribution changes during the neonatal period. There is abundant data on EID of gentamicin in neonates <7 days but data on optimal gentamicin dosing in preterm neonates >7 days is lacking. Objective(s): To determine if EID of gentamicin achieves therapeutic serum trough (<2 mug/mL) and peak (5 mug/mL to 12 mug/mL) levels in premature neonates <32 weeks gestational age (GA) and >7 days of age. Design/Methods: Premature neonates <32 weeks GA and >7 days of age who received gentamicin for >5 days for suspected/confirmed sepsis were included. The dosing interval was based on 22 h level after first dose of 5 mg/kg. Trough and peak levels were drawn with the second dose if infant was receiving gentamicin 36 h or 48 h and with the third dose if gentamicin was 24 h. Exclusion criteria included major congenital anomalies or renal anomalies and renal dysfunction. Result(s): There were 39 infants with median GA of 27 weeks and mean birth weight of 902 g. At start of gentamicin, median postnatal age (PNA) was 27 days and mean birth weight 1338 g. Based on 22 h level, the dosing interval was 24 h in 30, 36 h in six and 48 h in three neonates. All infants had trough levels <2 mug/mL (median 0.9 mug/mL, range 0.4 mug/mL to 1.5 mug/mL) and peak levels >5 mug/mL (median 9.0 mug/mL, range 5.4 mug/mL to 15.1 mug/mL) with two infants having levels of 13.1 mug/mL and 15.1 mug/mL. There was no effect on urine output or serum creatinine levels after starting gentamicin. Of the available hearing screen results, one infant, the recipient twin of twin to twin transfusion, had sensorineural hearing loss. Using quantile regression to correct for confounders including GA, PNA correlated negatively with random, peak and trough levels (all P<0.01). Conclusion(s): In premature neonates <32 weeks GA and >7 days of age, EID of gentamicin using single 22 h level after the first dose for dosing interval achieves therapeutic serum peak and trough levels. (Figure presented) .