Integrating genomics, in vitro dynamic models, and next-generation mechanism-based modelling to investigate antibiotic combinations against multidrug-resistant bacterial pathogens

Bacterial species, including Pseudomonas aeruginosa, Klebsiella pneumoniae and Escherichia coli, which act opportunistically in vulnerable patient populations, such as patients with cystic fibrosis and hospitalised patients, are a major global health concern. The characteristics of these bacterial species mean they can evade most, if not all, currently available antibiotic treatments. Given the dire shortage of new antibiotics, it is essential to develop novel and effective treatment approaches. This thesis evaluated clinically available antibiotics, alone and in rationally selected combinations, against these bacterial species over time to identify effective antibiotic combination regimens and to characterise changes in bacterial genomic profiles.