Objective: There is no uniformity in the current recommendations of dosing regimen of gentamicin for neonates. We conducted a prospective, randomized, controlled trial to compare a once-daily dosing regimen to the twice-daily dosing regimen for neonates > or = 2500 g during the first 7 days after birth.
Study design: Infants > or = 2500 g admitted to the Neonatal Intensive Care Unit and prescribed gentamicin for suspected bacterial infection were randomized to receive either 4 mg/kg every 24 hours, study group (n=20), or a standard regimen of 2.5 mg/kg every 12 hours, control group (n=21). Serum gentamicin concentrations (SGCs) were followed and gentamicin pharmacokinetics calculated on all infants.
Results: Peak SGC 30 minutes after the first dose was 8.2+/-1.7 microg/ml in the study group, compared to 6.4+/-1.5 microg/ml in the control group (p=0.001). Ninety-five percent of study group infants, compared to 81% of the control group, had peak SGCs in therapeutic range after the first dose. Peak SGC at 48 hours (steady state) was 8.9+/-1.5 in the study group and 6.8+/-1.1 in the control group (p=0.0001). On further analysis, a significantly higher percentage of infants in the study group, compared to the control group, had peak SGCs in higher therapeutic ranges of 6 to 12 microg/ml as well as 8 to 12 microg/ml. None of the study infants, compared to six control infants, had trough SGCs > or = 2 microg/ml at steady state. Thus, none of the study group infants, versus six of the control group infants, needed a dosing adjustment at 48 hours (p=0.02, Fisher's exact test).
Conclusion: We found that 4 mg/kg gentamicin given every 24 hours achieved significantly higher peak SGCs and safe trough concentrations in all infants, compared to the twice-daily regimen of 2.5 mg/kg. We suggest that SGCs may not need to be followed in term infants prescribed a short course of this once-daily regimen for suspected early-onset sepsis if renal functions are normal.