Newborns and gentamicin--how much and how often?

Abstract

Aminoglycosides are widely used in the treatment of suspected or proven severe bacterial infections. Combined with � -lactam antibiotics, gentamicin provides synergic activity against the most commonly encountered pathogens in the first month of life, including the frequently isolated coagulase-negative staphylococci. The clinical use of aminoglycosides is limited, unfortunately, by their potential ototoxicity and nephrotoxicity. 1 Nevertheless, their concentration-dependent bactericidal action and post-antibiotic effect, antibacterial synergy with � -lactams and low cost, and the better understanding of risk factors associated with the use of these agents, are favourable points for their continued use. The risk of aminoglycosideinduced nephrotoxicity and ototoxicity, although controversial in newborns, must still be considered a potential hazard related to drug accumulation. 2‐4 Until substantial evidence proves otherwise, maintaining serum gentamicin concentrations within the accepted therapeutic range in newborns continues to be prudent. In order to obtain optimal therapeutic effect and to prevent potential toxicity associated with high post-dose and pre-dose gentamicin levels, gentamicin dosing has been determined taking into consideration the newborn’s weight, gestational age, post-natal age, post-conceptional age (gestational age + post-natal age), renal function [primarily glomerular filtration rate (GFR)], plasma creatinine concentration and last, but not least, the pharmacokinetics of the drug. The mean values (� S.D.) of the following pharmacokinetic parameters have been calculated for gentamicin: elimination rate constant, half-life, volume of distribution and clearance. The correlation between estimated gestational age or birth weight and these parameters has also been determined by regression analysis. Various target gentamicin concentrations based on standard practice guidelines to maximize efficacy and to prevent toxicity are: 5 (i) pre-dose