Evaluation of Dosing Guidelines for Gentamicin in Neonates and Children

Author:

Hollander Esther M.1,van Tuinen Eline L.1,Schölvinck Elisabeth H.2,Bergman Klasien A.3,Bourgonje Arno R.4ORCID,Gracchi Valentina5ORCID,Kneyber Martin C. J.6,Touw Daan J.17ORCID,Mian Paola1ORCID

Affiliation:

1. Department of Clinical Pharmacy and Pharmacology, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

2. Department of Pediatric Infectious Diseases, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

3. Division of Neonatology, Department of Pediatrics, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

4. Department of Gastroenterology and Hepatology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, The Netherlands

5. Division of Pediatric Nephrology, Beatrix Children’s Hospital, University Medical Center Groningen, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

6. Division of Peadiatric Critical Care Medicine, Department of Paediatrics, Beatrix Children’s Hospital Groningen, University Medical Center Groningen, University of Groningen Hanzeplein 1, 9713 GZ Groningen, The Netherlands

7. Department of Pharmaceutical Analysis, Groningen Research Institute for Pharmacy, University of Groningen, Hanzeplein 1, 9713 GZ Groningen, The Netherlands

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.

Publisher

MDPI AG

Subject

Pharmacology (medical),Infectious Diseases,Microbiology (medical),General Pharmacology, Toxicology and Pharmaceutics,Biochemistry,Microbiology

Reference58 articles.

1. Kinderformularium (2022, November 30). Gentamicine. Available online: https://www.kinderformularium.nl/geneesmiddel/23/gentamicine.

2. Aminoglycosides: Activity and resistance;Glupczynski;Antimicrob. Agents Chemother.,1999

3. Treatment and outcome of Pseudomonas aeruginosa bacteraemia: An antibiotic pharmacodynamic analysis;Zelenitsky;J. Antimicrob. Chemother.,2003

4. Side effects of aminoglycosides on the kidney, ear and balance in cystic fibrosis;Prayle;Thorax,2010

5. Population Pharmacokinetics and Relationship Between Demographic and Clinical Variables and Pharmacokinetics of Gentamicin in Neonates;Stolk;Ther. Drug Monit.,2002

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