To inform rational dosing of antibiotics, traditional Therapeutic Drug Monitoring (TDM) with empiric dose adjustment of has been increasingly supplanted by the use of Model-Informed Precision Dosing (MIPD) software.
Our objective was to evaluate a model-informed precision dosing approach specifically designed to individualize empiric tobramycin dosing in adults with cystic fibrosis, and to compare target attainment between both the model-based and the empiric dosing approaches.
The BestDose MIPD-software has been used with a published population pharmacokinetic model of tobramycin. To evaluate the MIPD strategy, we used retrospective data from CF adults treated with tobramycin at our local CF center. Empiric dose adjustments from the clinical staff were examined.
Using a simulation-based methodology, individualized tobramycin doses that maximize the probability of attaining a Cmax/MIC ratio of 32 mg/L were retrospectively calculated, and compared with empiric dose adjustments.
Overall, 101 CF adults were evaluated. Tobramycin Cmax in patients were low (mean of 25.7 ± 5.6 mg/L). The percentage of patients predicted to achieve a Cmax/MIC of ≥ 32 mg/L was low (12.0 %, mean dose of 8.8 ± 1.3 mg/kg) with empiric dose adjustment. TDM with retrospective PK/PD modelling suggest increasing tobramycin dosing in a much larger number of patients (88.0 %, mean dose of 11.6 ± 2.5 mg/kg).
Tobramycin doses empirically corrected by clinicians after TDM were predicted to be still insufficient to achieve the efficacy target in most CF patients. Meanwhile a model-based dosing approach that individualizes the tobramycin dosing led to significantly improved achievement of expected target exposure levels in CF adults. Prospective clinical evaluation is warranted.