Narrative cv coming soon 

Abstract: The clinical cut-offs (pharmacokinetic (PK)/ pharmacodynamic (PD) targets) of teicoplanin remain undefined, especially regarding the unbound drug fraction. Since the unbound concentration is responsible for the pharmacological effect, dose individualization is advised to be based on unbound, and not total, concentrations. To optimize teicoplanin dosing and patient treatment, an integrated series of in vivo and in vitro studies was conducted to establish and validate teicoplanin unbound PK/PD thresholds.Teicoplanin total and unbound pharmacokinetics were characterized in ICU and haematology patients, with a specific focus on interindividual differences in exposure related to renal function and albumin levels. These unbound teicoplanin pharmacokinetics were subsequently simulated in a Hollow Fibre Infection Model in presence of clinically relevant bacterial strains to determine an unbound exposure threshold target which can be applied in a clinical setting. To validate this target we are now conducting a Therapeutic Drug Monitoring (TDM) trial using Model-Informed Precision Dosing to evaluate whether the adherence to this target can be improved by using TDM compared to currently employed standard dosing regimens. If proven reliable this individualized dosing strategy can be implemented in the clinic to enhance teicoplanin dosing and treatment.