Dynamic infection models, metabolomics and mechanism-based modelling to investigate pharmacodynamic challenges of Pseudomonas aeruginosa

The bacterial species known as Pseudomonas aeruginosa is a major cause of life-threatening infections in critically ill patients and patients with cystic fibrosis. The characteristics of this bacterium mean it can evade the effect of antibiotics, particularly when they are administered in a sub-optimal manner. Analysis of the relationship between antibiotic exposure and bacterial response over a time-course is essential in the development of new treatment approaches. In this thesis, clinically available antibiotics were tested, alone and in combination, against P. aeruginosa clinical isolates over time to identify rationalised antibiotic combination regimens.