Evaluation Strategies for Triple-Drug Combinations against Carbapenemase-Producing Klebsiella Pneumoniae in an In Vitro Hollow-Fiber Infection Model
Estefany Garcia, John K Diep, Rajnikant Sharma, Patrick O Hanafin, Cely S Abboud, Keith S Kaye, Jian Li, Tony Velkov, Gauri G Rao
CLINICAL PHARMACOLOGY & THERAPEUTICS | WILEY | Published : 2021
Mounting antimicrobial resistance to carbapenemase-producing Klebsiella pneumoniae (CPKP) highlights the need to optimize currently available treatment options. The objective of this study was to explore alternative dosing strategies that limit the emergence of resistance to preserve the utility of last-line antibiotics by: (i) evaluating the pharmacodynamic (PD) killing activity of simulated humanized exposures to monotherapy and two-drug and three-drug combinations against CPKP bacterial isolates with different resistance mechanisms; and (ii) optimizing polymyxin B (PMB) exposure simulated in the three-drug combination regimens to maximize the killing activity. Two CPKP clinical isolates (..View full abstract
Awarded by National Institute of Allergy and Infectious Diseases
Awarded by National Institute of General Medical Sciences of the National Institutes of Health
G.G.R., T.V., J.L., and K.K are supported by the National Institute of Allergy and Infectious Diseases, award number R01AI146241. E.G. was supported by the National Institute of General Medical Sciences of the National Institutes of Health, award number T32GM086330. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.