Towards optimization of temocillin exposure in haemodialysis patients : a translational approach from bedside-to-bench-to-bedside
(2019)
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- Abstract
- Infections are the second leading cause of death for patients with end-stage renal disease (ESRD). Temocillin, a beta-lactam antimicrobial agent, is an interesting therapeutic option for Gram-negative infections. However, temocillin pharmacokinetic (PK) data in the haemodialysis population is limited, and data on its dialysability with contemporary haemodialysers is inexistent. This thesis is in three parts. The first focuses on the development and validation of an analytical method for the quantification of temocillin concentrations in human serum. In the second, temocillin PK is characterised in the ESRD population based on data from a study conducted in a Belgian hospital. The licensed dosage regimens were found to be far below target, leading to an update of the Summary of Product Characteristics. Finally, population PK methodologies were used to investigate the performance of clinically practical dosing regimens and their ability to achieve set PK/PD targets. Model-based Monte Carlo simulations lead to an improved temocillin dosage regimen applicable in routine clinical practice and likely to meet contemporary treatment targets for this patient population. More generally, this thesis addresses the current need, acknowledged by regulatory bodies, to study PK/PD relationships for 'old-revived' antibiotics such as temocillin, including in specific patient populations for whom data is lacking. This thesis provides such data for ESRD patients and makes concrete propositions on how to optimise treatment in this population.
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Miranda Bastos, A. (2019). Towards optimization of temocillin exposure in haemodialysis patients : a translational approach from bedside-to-bench-to-bedside. https://hdl.handle.net/2078.5/54666