Evaluation of Dosing Guidelines for Gentamicin in Neonates and Children

Abstract

Although aminoglycosides are frequently prescribed to neonates and children, the ability to reach effective and safe target concentrations with the currently used dosing regimens remains unclear. This study aims to evaluate the target attainment of the currently used dosing regimens for gentamicin in neonates and children. We conducted a retrospective single-center cohort study in neonates and children receiving gentamicin between January 2019 and July 2022, in the Beatrix Children's Hospital. The first gentamicin concentration used for therapeutic drug monitoring was collected for each patient, in conjunction with information on dosing and clinical status. Target trough concentrations were ≤1 mg/L for neonates and ≤0.5 mg/L for children. Target peak concentrations were 8-12 mg/L for neonates and 15-20 mg/L for children. In total, 658 patients were included (335 neonates and 323 children). Trough concentrations were outside the target range in 46.2% and 9.9% of neonates and children, respectively. Peak concentrations were outside the target range in 46.0% and 68.7% of neonates and children, respectively. In children, higher creatinine concentrations were associated with higher gentamicin trough concentrations. This study corroborates earlier observational studies showing that, with a standard dose, drug concentration targets were met in only approximately 50% of the cases. Our findings show that additional parameters are needed to improve target attainment.

Keywords: children; dosage regimen; gentamicin; neonates; pharmacokinetics.

Figure 1

Flowchart indicating the total number of cycles, number of exclusions, reason for exclusion, total number of patients and gentamicin treatment cycles included, and stratification among the cohorts. BKZ: Beatrix Children’s Hospital, ECMO: extracorporeal membrane oxygenation.

Figure 2

Concentrations of gentamicin in neonates and children. (A) Neonates, (B) children. Blue circles represent a single-patient peak concentration, and red circles represent single-patient gentamicin trough concentrations (as delineated in Table 3). Dashed lines indicate the target concentrations.

Figure 3

Correlation of gentamicin trough concentrations with creatinine concentrations at the start of antibiotic treatment and at TDM. Deming regression of antibiotic trough concentrations with creatinine concentrations taken within 24 h before the start of gentamicin treatment (A), with residuals analysis (B); and within 24 h before the TDM sample (C), with residuals analysis (D). Circles represent single-patient creatinine and gentamicin trough concentrations. The solid line represents the linear regression line.

Figure 3

Correlation of gentamicin trough concentrations with creatinine concentrations at the start of antibiotic treatment and at TDM. Deming regression of antibiotic trough concentrations with creatinine concentrations taken within 24 h before the start of gentamicin treatment (A), with residuals analysis (B); and within 24 h before the TDM sample (C), with residuals analysis (D). Circles represent single-patient creatinine and gentamicin trough concentrations. The solid line represents the linear regression line.