Use of 4-mg/kg/24-Hour Empiric Aminoglycoside Dosing in Preoperative Neonates With Congenital Heart Disease

Brady S Moffett; Joseph W Rossano

Disclosures

The Annals of Pharmacotherapy. 2012;46(9):1193-1197. 

In This Article

Abstract and Introduction

Abstract

Background: Empiric dosing of gentamicin has not been evaluated in critically ill neonates with unrepaired congenital heart disease (CHD). Many factors may alter gentamicin pharmacokinetics in this patient population and there are few data describing gentamicin dosing regimens in this patient population.
Objective: To determine whether an empiric gentamicin dosing regimen for neonates achieves acceptable serum trough concentrations in neonatal patients with unrepaired CHD receiving alprostadil.
Methods: Term neonates with unrepaired CHD who received gentamicin for empiric treatment of sepsis were identified over a 3-year period. Patients were included if they received gentamicin 4 mg/kg/dose every 24 hours, were receiving alprostadil for maintenance of a patent ductus arteriosus, and had at least one gentamicin serum trough concentration determined. Patients were evaluated to determine whether they achieved a serum trough concentration of <1 mg/L, and differences in patient characteristics were noted for those who achieved an appropriate trough concentration and those who did not.
Results: Twenty-eight patients met study criteria, and 22% of patients had a trough gentamicin concentration of <1 mg/L at a mean (SD) time of 23.6 (0.3) hours after a dose. Few statistically significant differences in patient characteristics were noted for those who achieved an appropriate serum trough concentration and those who did not, and included Apgar scores at 1 minute and later day of life at admission.
Conclusions: Current empiric gentamicin dosing regimens may not be appropriate for critically ill neonates with unrepaired CHD. Routine serum concentration monitoring may be warranted in this population.

Introduction

Once-daily gentamicin dosing is widely used in neonates for empiric therapy of sepsis.[1–10] This strategy is thought to provide adequate serum drug concentrations for antimicrobial effects without increased toxicity. Still, the ideal once-daily gentamicin dosing regimen that will achieve therapeutic concentrations in neonatal patients is unknown.[9–11]

Many neonates with congenital heart disease (CHD) may receive empiric gentamicin therapy until an infectious cause is ruled out. Features of critically ill neonatal patients with CHD may alter the pharmacokinetics of gentamicin, resulting in suboptimal peak and trough concentrations. These features include the use of diuretics, decreased kidney perfusion, and the maintenance of a patent ductus arteriosus (PDA) with alprostadil.[9,10,12–14]

Current dosing guidelines recommend that dosing intervals should be prolonged in neonates with birth depression (Apgar score ≤6), birth hypoxia/birth asphyxia, or CHD.[9,10] However, there have been no data published evaluating a once-daily dosing scheme in patients with unrepaired CHD. Determination of gentamicin pharmacokinetic characteristics in this patient population is important due to the incidence of CHD and the potential renal morbidity incurred from elevated trough concentrations or subtherapeutic peak concentrations. This patient population may be at a high risk for toxicities associated with aminoglycosides due to altered hemodynamics and the concomitant use of medications that may potentiate renal toxicity, such as angiotensin converting enzyme inhibitors and loop diuretics.[15–17]

The primary objective of this study was to determine whether an empiric gentamicin dosing regimen for neonates achieves acceptable serum trough concentrations in neonatal patients with unrepaired CHD receiving alprostadil. Additionally, we sought to determine patient-specific factors for decreased gentamicin clearance in neonatal patients with unrepaired CHD receiving alprostadil.

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