We developed a simplified gentamicin dosing protocol for all neonates using a loading dose and once-daily dosing that would have an equal or lower incidence of toxicity and an equal or improved effectiveness compared with a regimen with no loading dose that included use of divided daily dosing.
All neonatal intensive care unit patients with a postnatal age ≤7 days and started on gentamicin therapy at the discretion of the attending neonatologist were evaluated in this comparative cohort study. All peak and trough serum drug levels (SDL), pertinent demographic data, and markers of potential nephrotoxicity, ototoxicity, and cure were tracked prospectively during 132 consecutive, nonrandomized courses of therapy on a new gentamicin protocol. These were compared with data retrieved retrospectively throughout 103 consecutive, nonrandomized courses of therapy in a control group.
Initial measured peak SDL were higher (7.8 ± 1.1 μg/mL vs 6.1 ± 1.0 μg/mL) and trough SDL were lower (0.9 ± 0.2 μg/mL vs 2.7 ± 0.6 μg/mL) in the protocol term subset, compared with the control term subset (gestational age, ≥37 weeks; weight, ≥2500 g). One hundred percent of the initial and maintenance peak SDL in term protocol neonates were 5 to 12 μg/mL; compared with 84% of the initial and 61% of maintenance peak SDL in the term control group. One hundred percent of the initial and maintenance trough SDL were in the desired range of <2 μg/mL in term protocol neonates; compared with 70% of the initial and 94% of maintenance trough SDL in the term control group. No significant differences were found in any SDL in low birth weight neonates (gestational age <37 weeks or weight <2500 g and >1500 g) in the protocol compared with the control group. The very low birth weight (weight <1500 g) protocol neonates had a significantly higher mean initial trough SDL (2.3 ± 0.7 μg/mL vs 1.5 ± 0.6 μg/mL) and a lower incidence of initial trough SDL <2.0 μg/mL (30% vs 95%) than very low birth weight neonates in the control group. No differences were seen between groups in incidence of significant rise in serum creatinine or failure of hearing screen.
A loading dose followed by once-daily dosing was shown to result in SDL in the safe and therapeutic range in all term neonates in this study. In low birth weight neonates, this regimen resulted in peak and trough SDL throughout therapy that were similar to those observed in the control group. Delaying the initiation of maintenance once-daily dosing until 36 to 48 hours after the loading dose would be expected to result in a higher incidence of initial trough SDL in target range for very low birth weight neonates.