From historical dosing to precision dosing: Modernising tobramycin monitoring in people with cystic fibrosis.
8 affiliations
- 1Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Brisbane, QLD, Australia.
- 2Pharmacy Department, The Prince Charles Hospital, Brisbane, QLD, Australia.
- 3Faculty of Health, Medicine and Behavioural Science, The University of Queensland, Brisbane, QLD, Australia.
- 4Lung Inflammation & Infection, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
- 5Department of Infectious Diseases, The Prince Charles Hospital, Brisbane, QLD, Australia.
- 6Department of Thoracic Medicine, The Prince Charles Hospital, Brisbane, QLD, Australia.
- 7Adult Cystic Fibrosis Centre, The Prince Charles Hospital, Brisbane, QLD, Australia. [email protected].
- 8Faculty of Health, Medicine and Behavioural Science, The University of Queensland, Brisbane, QLD, Australia. [email protected].
Abstract
Background
Historical therapeutic drug monitoring (TDM) strategies for intravenous tobramycin in people with cystic fibrosis (pwCF) were developed in the pre-CFTR modulator era and relied predominantly on clearance-based monitoring to minimise toxicity. Contemporary pwCF demonstrate greater variability in body composition and clinical phenotype, potentially limiting the applicability of historical dosing approaches.Methods
In December 2024, our adult cystic fibrosis centre implemented Bayesian-guided TDM (TDMx®) for intravenous tobramycin. Two serum concentrations obtained during the first dosing interval were used to estimate maximum concentration (Cmax), minimum concentration (Cmin), and 24-hour area under the concentration-time curve (AUC0- 24), enabling model-informed dose individualisation. Outcomes were evaluated in 46 pwCF receiving intravenous tobramycin for pulmonary exacerbations.Results
Prior to implementation, 74% of pwCF had not undergone formal dose review for more than three years. Following introduction of Bayesian monitoring, 98% received 24-hourly dosing compared with 33% under the historical protocol. Among pwCF with previous admissions, 72% required dose adjustment. Target Cmax (16-20 mg/L) was achieved in 65.2% of participants, while only 17.4% achieved the target AUC0- 24 (> 70 mg·h/L); no participant exceeded the upper AUC target of 100 mg·h/L. Thirteen pwCF who would previously have undergone dose reduction because of levels of >1 mg/L at 12 h demonstrated appropriate exposure on Bayesian assessment (mean Cmax 17 mg/L; mean AUC 74 mg·h/L). No nephrotoxicity attributable to the protocol was observed.Conclusions
Bayesian-guided TDM was feasible, safe, and substantially altered tobramycin prescribing practice. It identified pwCF at risk of both inappropriate dose reduction and underexposure, supporting precision dosing in the evolving CF population.
Related
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BibTeX
@article{johnson2026from,
title = {{From historical dosing to precision dosing: Modernising tobramycin monitoring in people with cystic fibrosis.}},
author = {Ellie Johnson and Michael Williams and Daniel Henderson and Timothy Riddles and David Reid and Daniel Smith and Andrew Burke and Ieuan Edward Shepherd Evans},
journal = {European journal of clinical pharmacology},
year = {2026},
month = oct,
doi = {10.1007/s00228-026-04205-5},
url = {https://europepmc.org/article/MED/42891690},
note = {CC BY},
}
RIS
TY - JOUR
TI - From historical dosing to precision dosing: Modernising tobramycin monitoring in people with cystic fibrosis.
AU - Ellie Johnson
AU - Michael Williams
AU - Daniel Henderson
AU - Timothy Riddles
AU - David Reid
AU - Daniel Smith
AU - Andrew Burke
AU - Ieuan Edward Shepherd Evans
PY - 2026
DA - 2026/10/17
JO - European journal of clinical pharmacology
DO - 10.1007/s00228-026-04205-5
UR - https://europepmc.org/article/MED/42891690
AB - Background Historical therapeutic drug monitoring (TDM) strategies for intravenous tobramycin in people with cystic fibrosis (pwCF) were developed in the pre-CFTR modulator era and relied predominantly on clearance-based monitoring to minimise toxicity. Contemporary pwCF demonstrate greater variability in body composition and clinical phenotype, potentially limiting the applicability of historical dosing approaches.Methods In December 2024, our adult cystic fibrosis centre implemented Bayesian-guided TDM (TDMx®) for intravenous tobramycin. Two serum concentrations obtained during the first dosing interval were used to estimate maximum concentration (Cmax), minimum concentration (Cmin), and 24-hour area under the concentration-time curve (AUC0- 24), enabling model-informed dose individualisation. Outcomes were evaluated in 46 pwCF receiving intravenous tobramycin for pulmonary exacerbations.Results Prior to implementation, 74% of pwCF had not undergone formal dose review for more than three years. Following introduction of Bayesian monitoring, 98% received 24-hourly dosing compared with 33% under the historical protocol. Among pwCF with previous admissions, 72% required dose adjustment. Target Cmax (16-20 mg/L) was achieved in 65.2% of participants, while only 17.4% achieved the target AUC0- 24 (> 70 mg·h/L); no participant exceeded the upper AUC target of 100 mg·h/L. Thirteen pwCF who would previously have undergone dose reduction because of levels of >1 mg/L at 12 h demonstrated appropriate exposure on Bayesian assessment (mean Cmax 17 mg/L; mean AUC 74 mg·h/L). No nephrotoxicity attributable to the protocol was observed.Conclusions Bayesian-guided TDM was feasible, safe, and substantially altered tobramycin prescribing practice. It identified pwCF at risk of both inappropriate dose reduction and underexposure, supporting precision dosing in the evolving CF population.
SN - 0031-6970
SN - 1432-1041
ER -