Targeting Lower Serum Trough Concentrations: A New Gentamicin Dosing Strategy for Suspected Neonatal Early-Onset Sepsis

J Pediatr Pharmacol Ther. 2023;28(1):71-77. doi: 10.5863/1551-6776-28.1.71. Epub 2023 Feb 3.

Abstract

Objective: Neonatal gentamicin dosing algorithms are not designed to achieve serum trough concentrations ≤1 mcg/mL. The purpose of our study was to evaluate a new gentamicin algorithm based on serum creatinine (SCr) and gestational age (GA) designed to achieve serum gentamicin trough concentrations ≤1 mcg/mL.

Methods: A retrospective cohort study was conducted in a level IIIB neonatal intensive care unit. The incidence of elevated serum gentamicin troughs for this study was compared with the center's previously published results to evaluate the proposed dosing algorithm. Patients were included if gentamicin was administered within the first 7 days of life and a serum gentamicin trough concentration and a baseline SCr concentration were obtained. Patients were further subdivided into groups based on GA for data analysis: ≤30 weeks (group 1), 30-34 weeks (group 2), and ≥35 weeks (group 3). The SCr was considered mildly elevated (0.81-0.99 mg/dL) or elevated (≥1 mg/dL). The respective outcomes between the post-algorithm and control groups were examined using intention-to-treat analysis and Bayesian modeling to calculate rate differences.

Results: Of the 2377 patients evaluated, 366 met the inclusion criteria. Significantly lower percentages of elevated serum gentamicin troughs were noted in groups 2 and 3 subsequent to the implementation of the dosing algorithm with 16% and 15% lower rate differences, respectively. Regardless of GA, there were significantly fewer elevated serum troughs in the post-implementation groups than in the control with mildly elevated and elevated SCr p < 0.001.

Conclusions: Using a dosing algorithm based on SCr significantly reduced the number of elevated serum trough rates in neonates with a GA greater than 30 weeks.

Keywords: algorithm; creatinine; early-onset sepsis; gentamicin; gestational age; neonatal; neonate; nomogram.

Grants and funding

Disclosures. The authors have nothing to disclose.