Clinical Pharmacokinetics of Gentamicin in Neonates

Abstract

Gentamicin is a bactericidal aminoglycoside antibiotic, it inhibits the protein synthesis. Gentamicin is active against the majority of aerobic gram-negative bacilli such as Pseudomonas, Klebsiella and Escherichia coli. The gentamicin doses are 3 mg/kg once-daily for preterm newborns 35 weeks of gestation. The monitoring of gentamicin serum concentration is recommended when infants are treated for 48 hours or more. The gentamicin peak concentration must be at least 8 times the minimum inhibitory concentration (MIC) to be bactericidal and the gentamicin trough concentration must be < 2 µg/ml to avoid ototoxicity and nephrotoxicity.Once-daily dosing of gentamicin (4 mg/kg), is preferred than twice-daily dose of 2.5 mg/kg gentamicin. A gentamicin loading dose (4 mg/kg), followed by once-daily dosing of 2.5 mg/kg yields safe and target range in neonates. An extended dosing interval of 48-hour (5 mg/kg gentamicin), was compared with twice-daily dose of 2.5 mg/kg gentamicin. Infants in the 48-hour interval and in the twice-daily achieved peak gentamicin concentrations of 9.43 µg/ml and 6.0 µg/ml, respectively, (p<0.001), and trough gentamicin concentrations were 1.08 µg/ml and 1.54 µg/ml, respectively, (p<0.001). The infants born small for gestational age have a reduced gentamicin clearance, and a more prolonged gentamicin half-life than infants born appropriate for gestational age. Patent ductus arteriosus, extracorporeal membrane oxygenation, therapeutic hypothermia, and asphyxia reduce the gentamicin clearance.