Rational polymyxin triple combination therapy against polymyxin-resistant multidrug-resistant (MDR) Klebsiella pneumoniae using a system pharmacology approach

Antibiotic resistance is a serious threat to global health. Due to the lack of new antibiotics and emergence of resistance to the last-line polymyxins, developing effective antibiotic combinations against 'superbugs' is of utmost importance. This thesis is the first to identify a synergistic polymyxin-based triple combination against multidrug-resistant Klebsiella pneumoniae, elucidate the potential mechanism of enhanced antibacterial killing, and propose a potential effective dosage regimen for critically-ill patients. This thesis has made a substantial contribution to polymyxin pharmacology and the optimisation of combination therapy for the treatment of life-threatening infections caused by multidrug-resistant K. pneumoniae.