Treatment of multidrug-resistant Acinetobacter baumannii with novel combinations of polymyxin B and other non-antibiotic drugs

Multidrug-resistant Acinetobacter baumannii are increasingly becoming problematic to the healthcare system globally due to limited effective antibiotics. This thesis investigated the potential of repositioning non-antibiotic drugs for use in combination with polymyxin B to enhance the bacterial killing of this last-line antibiotic against these pathogens and prevent the emergence of polymyxin resistance. The in vitro and in vivo studies identified numerous promising non-antibiotic candidates with synergistic antimicrobial activity against multiple Gram-negative bacteria including A. baumannii. The metabolomic studies revealed potential bacterial killing mechanisms of a novel combination and transcriptomic studies discovered numerous potential targets for future repositioning of non-antibiotic drugs.