Antimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health. Optimising antimicrobial treatment... Show moreAntimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health. Optimising antimicrobial treatment strategies in patients offers an important direction to address this challenge. In this thesis, we describe how quantitative characterisation of the drug, the pathogen, and the patients, and how these three factors interact, can help to achieve this goal. To this end, we used a combination of state-of-the-art in silico model-based approaches to analyse and integrate experimental data from in vitro models, and clinical data from healthy volunteers and patients. We developed models describing infection site drug exposure, antimicrobial resistance evolution, and host response biomarker dynamics. We explored the impact of infection on pulmonary pharmacokinetics, evolutionary-based treatment strategies, and the utility host response biomarker for treatment monitoring. The work in this thesis builds towards developing novel strategies to optimise antimicrobial treatments and showcases the importance on interdisciplinary collaborations. Show less
Hoek, B. van; Rooij, B.J. de; Verspaget, H.W. 2012
