Journal of Targeted Drug Delivery

Clinical Pharmacology of Gentamicin in Infants and Children

Author(s): Gian Maria Pacifici

Gentamicin is an aminoglycoside antibiotic and it is active against aerobic gram-negative bacilli such as Pseudomonas, Klebsiella, and Escherichia coli. Gentamicin should be co-administered with a β-lactam antibiotic. This antibiotic is rapidly bactericidal as it inhibits bacterial cell protein synthesis. Bacterial killing is concentration dependent: the higher the concentration, the greater the rate of bacterial killing. Dosing recommendations are based on: (1) higher gentamicin peak concentrations, (2) post-antibiotic effect on bacterial killing, especially when treating concurrently with a β-lactam antibiotic, and (3) less toxicity with less frequent gentamicin dosing, due to low renal gentamicin accumulation. When gentamicin trough concentration is > 2 μg/ml, intervals among gentamicin doses should be extended to yield gentamicin trough concentration < 2 μg/ml. In infants, gentamicin dose should be 4 – 5 mg/kg. Once-daily gentamicin dosing is preferred than twice- or thrice-daily gentamicin administration. Once-daily gentamicin dosing yields lower trough and higher peak gentamicin concentrations. The recommended peak and trough gentamicin serum concentrations range from 5 to 12 μg/ml, and from 0.5 to 1 μg/ml, respectively. In very-low-birth weight, gentamicin half-life and distribution volume are 12.9 hours and 0.72 l/kg, respectively. In small-for-gestational age infants, with an age ≤ 7 days of life, gentamicin half-life is longer, and clearance is lower than in infants appropriate-for-gestational age. Gentamicin increases the risk of hearing loos, and causes renal dysfunction. Ototoxicity rate in preterm infant’s runs at 2-15% compared to 0.3% in full-term infants and it is permanent in 2-3% of cases, whereas nephrotoxicity is transient. Some bacteria may become resistant to gentamicin. The aim of this study is to review the published data on effects, pharmacokinetics, and bacterial-resistance of gentamicin in infants and children.




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