Pharmacokinetics of Aminoglycosides in the Newborn

Johannes      N. van den Anker; Karel      Allegaert

Abstract

Aminoglycosides have played a major role in antimicrobial therapy since their discovery in the 1940s. Their bactericidal efficacy in gram-negative infections, synergism with beta-lactam antibiotics, limited bacterial resistance, and low cost have given these agents a firm place in antimicrobial treatment. After penicillins, aminoglycosides are the most commonly used drugs in the neonatal intensive care unit. While the pharmacodynamic action on the bacterial target is obviously the same in neonates as compared to children and adults, dramatic differences exist in terms of pharmacokinetics. Renal function is the most important determinant in respect to the elimination of aminoglycosides and, depending on the age and development of the newborn infant, dramatic changes in renal clearing capacity have been documented. The incorporation of this knowledge about the developing kidney has, very recently, resulted in a revised aminoglycoside dosing guideline for use in newborn infants. This article will therefore address the rationale behind this new dosing regimen and also explain why this has resulted in clinically important changes in how to perform therapeutic drug monitoring of aminoglycosides in neonates to ensure safe and effective use of these frequently used medicines in this vulnerable population.

Keywords: Aminoglycosides, neonates, pharmacokinetics, therapeutic drug monitoring, antimicrobial therapy, developing kidney, polycationic drugs, minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC)