New Delhi metallo-β-lactamase (NDM) producing Klebsiella pneumoniae are multidrug-resistant (MDR) and classified as an Urgent Threat by the US Centers for Disease Control and Prevention. Polymyxins remain effective as a last-line therapy for infections caused by MDR Gram-negative bacteria. However, resistance to polymyxins can emerge with monotherapy. As polymyxin-induced nephrotoxicity is the major dose-limiting adverse effect, combination therapy with other antibiotics is warranted to preserve the efficacy of polymyxins whilst minimising the emergence of resistance. This thesis focuses on identifying novel synergistic polymyxin combinations against NDM-producing K. pneumoniae and elucidating mechanisms of synergy at the systems level.
Principal supervisorJian Li
Additional supervisor 1Tony Velkov
Additional supervisor 2Phillip Bergen
Year of Award2017
Department, School or CentreMicrobiology
CourseDoctor of Philosophy
FacultyFaculty of Medicine Nursing and Health Sciences