Polymyxin triple combinations against polymyxin-resistant, multidrug-resistant KPC-producing Klebsiella pneumoniae
Su Mon Aye, Irene Galani, Heidi Yu, Jiping Wang, Ke Chen, Hasini Wickremasinghe, Ilias Karaiskos, Phillip J Bergen, Jinxin Zhao, Tony Velkov, Helen Giamarellou, Yu-Wei Lin, Brian Tsuji, Jian Li
Antimicrobial Agents and Chemotherapy | American Society for Microbiology | Published : 2020
Resistance to polymyxin antibiotics is increasing. Without new antibiotic classes, combination therapy is often required. We systematically investigated bacterial killing with polymyxin-based combinations against multidrug-resistant (including polymyxin-resistant), carbapenemase-producing Klebsiella pneumoniae. Mono, double and triple combination therapies were compared to identify the most efficacious treatment using static time-kill studies (24h, six isolates), an in vitro pharmacokinetic/pharmacodynamic model (IVM; 48h, two isolates), and the mouse thigh infection model (24h, six isolates). In static time-kill studies, all monotherapies (polymyxin B/rifampicin/amikacin/meropenem/minocycli..View full abstract
Awarded by National Institute of Allergy and Infectious Diseases of the National Institutes of Health
J.L. 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 AI132681). J.L. and T.V. are also supported by the Australian National Health and Medical Research Council (NHMRC) as Principal Research and Career Development Level 2 Fellows, respectively. S.M.A. thanks the Myanmar Government for providing the Presidential Scholarship.