Developing novel bacteriophage-antibiotic combination therapy against multidrug-resistant Klebsiella pneumoniae

Antibiotic resistance is a global health threat and effective alternatives are urgently need to treat critical nosocomial pathogens including Klebsiella pneumoniae. A promising strategy that is gaining popularity is the use of bacteriophages (phages). However, emergence of resistance to phages is rapid and combination of phages with antibiotics has been increasingly investigated. In this study, new phages were isolated and characterised, and their combination with antibiotics was evaluated to reduce the resistance and maximise bacterial killing in vitro and in vivo. Mechanisms underpinning phage resistance were examined using genome sequencing and molecular microbiology. The mechanistic findings of enhanced bacterial killing with phage-ceftazidime/avibactam combination provide important information for treating critically-ill patients with multidrug-resistant K. pneumoniae infections. This PhD project will contribute to the development of effective phage therapy in clinic.