Extended-Interval Gentamicin Administration In Neonates = 34 Weeks Gestational Age
Gladys El-Chaar, Department of Clinical Pharmacy Practice, College of Pharmacy and Allied Health Professions, Tingnong Supaswud, and Susana Castro-Alcaraz, Neonatology, Schneider Children's Hospital, New Hyde Park
Abstract
Objectives: Extended-interval gentamicin administration (EIGA) has been adopted in neonates to maximize the drug’s pharmacodynamics and minimize its toxicity. Neonatal guidelines for EIGA dosing derived from the literature remain complicated. Our aim was to simplify them. Our hypothesis is that using a uniform gentamicin dose of 5 mg/kg IV every 36 hours for all neonates will reduce the number of elevated trough serum gentamicin concentrations (defined as = 2 mg/L), from approximately 50% (from a retrospective chart review) to 10%. A sample size of 23 neonates in each group was needed to detect this difference. Other objectives were to improve gentamicin’s pharmacodynamics and safety while simplifying its dosing.
Methods
This prospective, randomized, controlled study compared traditional dosing (control group) to EIGA (study group) in neonates >34 weeks gestational age (GA). Another study aim of neonates = 34 weeks GA is still in progress. Traditional dosing entails using a loading dose and multiple daily dosing. Inclusion criteria: neonates >34 weeks GA and < 6 months postnatal age. Exclusion criteria: neonates previously enrolled or endocarditis. Hearing screens and renal function parameters were closely monitored.
Results
46 neonates were enrolled, 23 in each group. Overall, elevated trough concentrations are reported in 0% vs 39% in the EIGA and traditional groups, respectively. Cmax and AUC achieved were 10.9±1.86 mg/L vs 6.83±1.33 mg/L and 161.38±29.11 vs 89±26.38 mg/hr/L in the EIGA and traditional groups, respectively. One patient in the traditional group failed the hearing screen whereas none did in the EIGA group. One child in the EIGA group had transient elevation in serum creatinine levels. None of the patients had a documented gram-negative sepsis.
Conclusions
A gentamicin dose of 5 mg/kg IV every 36 hours in neonates > 34 weeks GA improved the drug's pharmacokinetics and possibly pharmacodynamics, was simple, and did not increase the incidence of adverse effects.