Evaluation of a netilmicin-loading dose in very low birthweight infants

The bactericidal efficacy of aminoglycosides is directly related to maximum serum concentrations, particularly the initial one. Therefore, several groups have recommended an aminoglycoside loading dose. Our goal was to develop a simplified dosage regimen for preterm infants which would result in therapeutic maximum serum concentrations early in the course of therapy.

Open, noncomparative study during November 2000 to April 2001. The modified netilmicin-dosing protocol included a loading dose of 5 mg/kg in the first week of life, followed by a maintenance regimen of 3.5 mg/kg every 24 h. After the first week of life the corresponding doses were 6 (loading) and 5 mg/kg (maintenance). A peak level was measured 30 min after the second dose, and a trough level immediately before the third dose.

Thirty-five very low birthweight infants (mean birthweight 876 +/- 170, range 536-1,385 g; mean gestational age 26 +/- 1.8, range 23-30 weeks) who had 46 episodes of netilmicin treatment were included in the analysis. Mean netilmicin peak and trough values were 15.9 +/- 3.7 (range 8.9-28.9) and 3.4 +/- 1.3 (range 1.0-7.8) micromol/l, respectively. Ninety-one percent of all peak levels were within the targeted range of > or =10 micromol/l. Eleven trough values (24%) were > or =4 micromol/l: in 7 instances netilmicin was administered within the first week of life, 5 of these patients had concomitant indomethacin treatment. Only 1 of the 35 neonates had a rise in serum creatinine of > or =0.5 mg/dl during netilmicin therapy. Hearing evaluations were performed in 25 of the 29 surviving infants at discharge home, all of which gave normal results.

The new netilmicin-dosing protocol yielded therapeutic maximum serum concentrations in 91% of cases after the second dose. However, a significant number of very low birthweight infants had elevated trough levels, particularly when netilmicin was administered in the first week of life with concomitant indomethacin treatment. We speculate that a longer interval between the loading dose and the first maintenance dose would result in fewer elevated trough levels with a similarly high number of therapeutic peak levels.