Optimal Gentamicin Therapy in Preterm Neonates Includes Loading Doses and Early Monitoring

Abstract

Recent studies have suggested the inadequacy of an initial gentamicin 2.5 mg/kg standard dose in neonates and the need for a loading dose. The purpose of this prospective, randomized study was to compare initial peak and initial trough serum gentamicin concentrations (SGC) in neonates after a standard dose (2.5 mg/kg) or a loading dose (4 mg/kg) on the first day of life. A secondary objective of the study was to evaluate the use of two SGC drawn after the first dose in designing individualized dosage regimens, despite the many changes in gentamicin disposition that occur over the first week of life. Forty infants admitted to the NICU were randomized to receive either 2.5 or 4 mg/kg gentamicin. Individual gentamicin pharmacokinetic parameters were determined after the first dose. Initial peak SGC were > 5 mcg/ml in only 6% of neonates receiving 2.5 mg/kg, versus 94% of neonates receiving 4 mg/kg. The initial trough after the first dose was < 2 mcg/ml in 100% of patients receiving 2.5 mg/kg and only 39% of patients receiving 4 mg/kg. Using two SGC after the first dose successfully predicted steady state peaks in 13/16 infants and steady state troughs in 14/16 infants. Thus, standard treatment of 2.5 mg/kg gentamicin yields initial peak serum gentamicin concentrations < 5 mcg/ml in neonates while a 4 mg/kg gentamicin loading dose, combined with pharmacokinetic monitoring after the first dose, optimizes gentamicin therapy in neonates.

Clinical pharmacokinetics of aminoglycosides in the neonate: a review

“…Some authors suggested using a loading dose of 4-5 mg/ kg to shorten the time between the first dose of gentamicin and the time when gentamicin therapeutic serum concentration is reached [26][27][28][29]. The introduction of once-daily Loading dose of 5 mg/kg followed by a maintenance dose of 3.5 mg/kg f Loading dose of netilmicin of 5 mg/kg followed by maintenance dose of 5 mg/kg (body weight 2,000-2,500 g), 4 mg/kg (body weight 1,500-2,000 g), 3 mg/kg (body weight 1,000-1,500 g), 1.5 mg/kg (body weight 1,000-1,500 g) and 1 mg/kg (body weight <1,000 g) dosing and the extended interval between dose regimens, which require 4-5 mg/kg of gentamicin, makes the use of the loading dose unnecessary.…”

Pharmacokinetic Outcomes of a Simplified, Weight‐Based, Extended‐Interval Gentamicin Dosing Protocol in Critically Ill Neonates

“…[2][3][4] Protocols for initial gentamicin dosage regimens in neonates are often complex, as they incorporate multiple variables such as birth weight, gestational age at birth, postnatal age, and other ontogenic qualities and clinical risk factors. [5][6][7][8][9][10][11][12][13][14][15] Of these, birth weight is strongly correlated with gestational age at birth, and it remains a more consistent, sensitive, and precise predictor of gentamicin clearance in neonates than does gestational age at birth, postnatal age, or serum creatinine concentration (S cr ), making birth weight an attractive and easily retrievable choice for use in a neonatal gentamicin dosing protocol. 4,16 Simplified protocols are also less prone to dosing error than are more complex protocols.…”

A randomised, controlled trial of once daily and multi-dose daily gentamicin in young Kenyan infants

“…Early studies suggest dose adjustment on the basis of both gestation and postnatal age, [15][16][17][18] and use of a ''loading dose'' is recommended. 19 Extrapolation of the results of detailed, developed country pharmacokinetic studies to resource poor settings may also be difficult. In one study where it is explicitly reported, almost 20% of infants had dose adjustments made during a study of once daily treatment as a result of drug concentration results.…”