Novel Polymyxin Combination with the Antiretroviral Zidovudine Exerts Synergistic Killing against NDM-Producing Multidrug-Resistant Klebsiella pneumoniae
Yu-Wei Lin, Nusaibah Abdul Rahim, Jinxin Zhao, Mei-Ling Han, Heidi H Yu, Hasini Wickremasinghe, Ke Chen, Jiping Wang, David L Paterson, Yan Zhu, Gauri G Rao, Qi Tony Zhou, Alan Forrest, Tony Velkov, Jian Li
Antimicrobial Agents and Chemotherapy | AMER SOC MICROBIOLOGY | Published : 2019
Polymyxins are used as a last-line therapy against multidrug-resistant (MDR) New Delhi metallo-β-lactamase (NDM)-producing Klebsiella pneumoniae However, polymyxin resistance can emerge with monotherapy; therefore, novel strategies are urgently needed to minimize the resistance and maintain their clinical utility. This study aimed to investigate the pharmacodynamics of polymyxin B in combination with the antiretroviral drug zidovudine against K. pneumoniae Three isolates were evaluated in static time-kill studies (0 to 64 mg/liter) over 48 h. An in vitro one-compartment pharmacokinetic/pharmacodynamic (PK/PD) model (IVM) was used to simulate humanized dosage regimens of polymyxin B (4 mg/lit..View full abstract
Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health
Awarded by NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES
J.L., G.G.R., A.F., and T.V. are supported by a research grant from the National Institute of Allergy and Infectious Diseases of the National Institutes of Health (R01 AI111965). Y.-W.L. and M.-L.H. are recipients of the 2018 Faculty Bridging Fellowship, Monash University. J.L. is an Australian National Health Medical Research Council (NHMRC) Principal Research Fellow and T.V. is an Australian NHMRC Industry Career Development Level 2 Research Fellow.