A Quantitative Examination and Comparison of the Ability of Australian Gentamicin Dosing Guidelines to Achieve Target Therapeutic Concentrations in Neonates
<b>Background:</b> Effective gentamicin dosing is crucial to the survival of neonates with suspected sepsis but requires a careful balance between attaining both effective peak and safe trough concentrations. We aimed to systematically compare existing gentamicin dosing guidelines for ne...
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2025-01-01
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| author | Luke E. Grzeskowiak Sheree Wynne Michael J. Stark |
| author_facet | Luke E. Grzeskowiak Sheree Wynne Michael J. Stark |
| author_sort | Luke E. Grzeskowiak |
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| description | <b>Background:</b> Effective gentamicin dosing is crucial to the survival of neonates with suspected sepsis but requires a careful balance between attaining both effective peak and safe trough concentrations. We aimed to systematically compare existing gentamicin dosing guidelines for neonates in Australia to determine the extent to which they reach therapeutic targets. <b>Methods:</b> Simulations of a single gentamicin dose to a virtual representative neonatal population according to each Australian guideline were performed using population pharmacokinetic modelling. We determined the proportion of neonates who would achieve peak gentamicin concentrations of ≥5 or ≥10 mg/L and trough concentrations of ≤1 or ≤2 mg/L. We calculated the probability of target attainment (PTA) according to gestation at birth (22 to 40 weeks) and postnatal age (1–7, 8–14, 15–21, 22–28 days). <b>Results:</b> Five unique dosing guidelines were identified. Guidelines varied considerably with respect to dose (4.5 to 7 mg/kg), dosing interval (24 to 48 h), and characteristics used to individualise dosing regimens (e.g., gestation at birth and postnatal age). Guidelines were satisfactory in routinely achieving effective peak concentrations ≥ 5 mg/L, but PTAs for effective peak concentrations ≥ 10 mg/L varied considerably from 5% to 100% based on dose, gestation, and postnatal age. PTAs for trough concentrations ≤ 1 mg/L ranged from 0% to 100%, being lowest among extremely preterm infants. <b>Conclusions:</b> Current Australian gentamicin guidelines demonstrate significant variability in their ability to achieve defined therapeutic targets, necessitating efforts to improve standardisation of dosing recommendations. Further research to define optimal pharmacodynamic targets in neonates with respect to clinical outcomes are also urgently warranted. |
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| institution | Kabale University |
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| series | Antibiotics |
| spelling | doaj-art-f4389f083fcf4d4a96d0959a9d7f91af2025-01-24T13:18:43ZengMDPI AGAntibiotics2079-63822025-01-011414810.3390/antibiotics14010048A Quantitative Examination and Comparison of the Ability of Australian Gentamicin Dosing Guidelines to Achieve Target Therapeutic Concentrations in NeonatesLuke E. Grzeskowiak0Sheree Wynne1Michael J. Stark2College of Medicine and Public Health, Flinders University, Adelaide 5042, AustraliaSA Pharmacy, Flinders Medical Centre, SA Health, Adelaide 5042, AustraliaAdelaide Medical School, Robinson Research Institute, The University of Adelaide, Adelaide 5005, Australia<b>Background:</b> Effective gentamicin dosing is crucial to the survival of neonates with suspected sepsis but requires a careful balance between attaining both effective peak and safe trough concentrations. We aimed to systematically compare existing gentamicin dosing guidelines for neonates in Australia to determine the extent to which they reach therapeutic targets. <b>Methods:</b> Simulations of a single gentamicin dose to a virtual representative neonatal population according to each Australian guideline were performed using population pharmacokinetic modelling. We determined the proportion of neonates who would achieve peak gentamicin concentrations of ≥5 or ≥10 mg/L and trough concentrations of ≤1 or ≤2 mg/L. We calculated the probability of target attainment (PTA) according to gestation at birth (22 to 40 weeks) and postnatal age (1–7, 8–14, 15–21, 22–28 days). <b>Results:</b> Five unique dosing guidelines were identified. Guidelines varied considerably with respect to dose (4.5 to 7 mg/kg), dosing interval (24 to 48 h), and characteristics used to individualise dosing regimens (e.g., gestation at birth and postnatal age). Guidelines were satisfactory in routinely achieving effective peak concentrations ≥ 5 mg/L, but PTAs for effective peak concentrations ≥ 10 mg/L varied considerably from 5% to 100% based on dose, gestation, and postnatal age. PTAs for trough concentrations ≤ 1 mg/L ranged from 0% to 100%, being lowest among extremely preterm infants. <b>Conclusions:</b> Current Australian gentamicin guidelines demonstrate significant variability in their ability to achieve defined therapeutic targets, necessitating efforts to improve standardisation of dosing recommendations. Further research to define optimal pharmacodynamic targets in neonates with respect to clinical outcomes are also urgently warranted.https://www.mdpi.com/2079-6382/14/1/48gentamicininfantnewbornprematurepharmacologypharmacokinetics |
| spellingShingle | Luke E. Grzeskowiak Sheree Wynne Michael J. Stark A Quantitative Examination and Comparison of the Ability of Australian Gentamicin Dosing Guidelines to Achieve Target Therapeutic Concentrations in Neonates Antibiotics gentamicin infant newborn premature pharmacology pharmacokinetics |
| title | A Quantitative Examination and Comparison of the Ability of Australian Gentamicin Dosing Guidelines to Achieve Target Therapeutic Concentrations in Neonates |
| title_full | A Quantitative Examination and Comparison of the Ability of Australian Gentamicin Dosing Guidelines to Achieve Target Therapeutic Concentrations in Neonates |
| title_fullStr | A Quantitative Examination and Comparison of the Ability of Australian Gentamicin Dosing Guidelines to Achieve Target Therapeutic Concentrations in Neonates |
| title_full_unstemmed | A Quantitative Examination and Comparison of the Ability of Australian Gentamicin Dosing Guidelines to Achieve Target Therapeutic Concentrations in Neonates |
| title_short | A Quantitative Examination and Comparison of the Ability of Australian Gentamicin Dosing Guidelines to Achieve Target Therapeutic Concentrations in Neonates |
| title_sort | quantitative examination and comparison of the ability of australian gentamicin dosing guidelines to achieve target therapeutic concentrations in neonates |
| topic | gentamicin infant newborn premature pharmacology pharmacokinetics |
| url | https://www.mdpi.com/2079-6382/14/1/48 |
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