Evaluation of an Empirical Dosing Schedule for Gentamicin in Neonates

Abstract

The standard gentamicin dosing recommendations for neonates appear to be inappropriate because they fail to consider the influence of neonatal development on gentamicin pharmacokinetics. Recent reports have emphasized that the standard regimens of 2.5 mg/kg q8-12h produce steady-state trough serum concentrations > 2 ",g/ml in up to 91 percent of preterm infants of less than 35 weeks' gestation. A new dosing schedule based on postconceptional age (PCA) was developed to provide a better guideline for initiating and maintaining gentamicin therapy in neonates: PCA greater than 34 weeks, 2.5 mg/kg iv qI2h; peA 28-34 weeks, 2.5 mg/kg iv ql6h; PCA less than 28 weeks, 2.5 mg/kg iv q24h. The new dosing schedule reduced the number of neonates with elevated trough concentrations (> 2 ",g/ml) from 68.4 percent to 33-40 percent. Pharmacokinetic parameters for gentamicin in the various PCA groups were determined. Volume of distribution was constant across age groups (0.5 ± 0.09 L/kg). Elimination rate constants (k el ) , half-lives, and clearance rates (CI) ranged from 0.069 ± 0.02 to 0.14 ± 0.04 h-I , 10.71 ± 2.92 to 6.04 ± 1.24 h, and 0.58 ± 0.25 to 0.93 ± 0.24 ml/kg/min, respectively. Significant relationships were found between k el and CI and patient age and weight; significant correlations were found between actual and estimated (based on PCA and weight) k el and Cl. Variability in k el and CI estimated was considerable in spite of the correlations. The observed variability stresses again the need for pharmacokinetic monitoring of gentamicin therapy in neonates. Drug Intell CUn Pharm 1988;22:618-22. GENTAMICIN IS COMMONLY USED in the treatment of neonatal sepsis and meningitis. Dosing guidelines currently used-to initiate and maintain gentamicin therapy in neonates are 2.5 mg/kg q12h for neonates less than one week of age or 2.5 mg/kg q8h for neonates greater than one week of age. These guidelines are designed to

Levofloxacin Use in the Neonate: A Case Series

“…All of the patients received multiple cultures and courses of antibiotics (Tables 1-6). Unless otherwise stated, antibiotic dosage followed recommendations appropriate for postmenstrual and postnatal age in Lexicomp (Pediatric and Neonatal Lexi-Drugs), 13 Neofax, 14 American Academy of Pediatrics Red Book, 15 or the primary literature [16][17][18][19] in a few cases. Antibiotics were adjusted as needed based on renal function and serum drug concentration.…”

An Updated Comparison of Drug Dosing Methods

“…Several studies have revised current dosing guidelines or made new dosing recommendations (Bloome et al 1988;Charlton et al 1986;Hemgren et al 1986;Kenyon et al 1990;Pons et al 1988;Reimche et al 1987). Carlstedt et al (1989) evaluated the predictive performance of a literature-derived dosing algorithm designed by the authors (n = 75) and the Bayesian feedback method (n = 36) for their ability to predict subsequent levels.…”