Optimization of gentamicin therapy in very low birth weight infants

In order to optimize gentamicin (G) therapy we studied G pharmacokinetics in 48 preterm infants (gest. age 31.6 ± 3.4, range 25-37 wk; birth weight 1.5 ± 0.5 kg, range 0.7-2.5 kg). They received IV G twice daily (5.2 ± 0.6 mg/kg/day). After at least 2 days of treatment trough and peak levels were measured for 2 successive doses. Trough levels were significantly higher in infants < 1 kg receiving 5 mg/kg/day than in other infants (1-2.5 kg) who received the same dose (3.1 ± 1.0 vs. 2.3 ± 0.5 μg/ml; p < 0.01). Mean G t 1/2 was significantly longer in infants under 1 kg than in those weighing 1-2.5 kg (7.9 ± 1.9 and 6.5 ± 1.6 hr, respectively; p < 0.01). These differences could be attributed to lower G clearance in infants < 1 kg (31 ± 6 vs. 39 ± 8 ml/kg/hr; p < 0.005). There was no difference in G distribution volume between < 1 kg and 1-2.5 kg infants (0.35 ± 0.07 and 0.38 ± 0.13 L/kg, respectively). A correlation was found between clearance and t 1/2 for the total group (r = 0.57, p < 0.01). No correlation was detected between BUN and clearance or between gestational age and clearance. Our data suggest that G dose in infants < 1 kg should be reduced to 3.5-4 mg/kg/day in order to avoid excessive levels associated with nephrotoxicity.