Polymyxin Combinations Combat Escherichia coli Harboring mcr-1 and blaNDM-5: Preparation for a Postantibiotic Era.

ABSTRACT: The rapid increase of carbapenem resistance in Gram-negative bacteria has resurrected the importance of the polymyxin antibiotics. The recent discovery of plasmid-mediated polymyxin resistance (mcr-1) in carbapenem-resistant Enterobacteriaceae serves as an important indicator that the golden era of antibiotics is under serious threat. We assessed the bacterial killing of 15 different FDA-approved antibiotics alone and in combination with polymyxin B in time-killing experiments against Escherichia coli MCR1_NJ, the first reported isolate in the United States to coharbor mcr-1 and a New Delhi metallo-β-lactamase gene (blaNDM-5). The most promising regimens were advanced to the hollow-fiber infection model (HFIM), where human pharmacokinetics for polymyxin B, aztreonam, and amikacin were simu

SUBMITTER: Bulman ZP 

PROVIDER: S-EPMC5527306 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature