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Deciphering the modes of action of polymyxins and the synergistic combinations against multidrug-resistant Gram-negative bacteria: a systems pharmacology approach

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posted on 02.10.2017, 22:13 by MOHD HAFIDZ BIN MAHAMAD MAIFIAH
Multidrug-resistant Gram-negative bacteria, particularly Acinetobacter baumannii and Pseudomonas aeruginosa present a significant threat to human health globally and polymyxins are increasingly used as the last-line defence. Polymyxin combination therapy has been strongly recommended, as pharmacokinetic/pharmacodynamic studies reveal that polymyxins often fail to achieve an effective exposure in vivo which potentially leads to the emergence of resistance. This thesis provides much-needed mechanistic insights into polymyxin action and synergistic combinations with other antibiotics using metabolomics and transcriptomics. This study highlights the significant potential of paradigm-shifting systems pharmacology in optimising antibiotic use. Overall, this project targets the urgent global medical challenge, antibiotic resistance.


Campus location


Principal supervisor

Jian Li

Additional supervisor 1

Darren J. Creek

Additional supervisor 2

Tony Velkov

Year of Award


Department, School or Centre

Drug Delivery, Disposition and Dynamics


Doctor of Philosophy

Degree Type



Faculty of Pharmacy and Pharmaceutical Sciences

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