Pharmacodynamics of dose-escalated 'front-loading' polymyxin B regimens against polymyxin-resistant mcr-1-harbouring Escherichia coli.

ABSTRACT:

Objectives

Gram-negative bacteria harbouring the mcr-1 plasmid are resistant to the 'last-line' polymyxins and have been reported worldwide. Our objective was to define the impact of increasing the initial polymyxin B dose intensity against an mcr-1 -harbouring strain to delineate the impact of plasmid-mediated polymyxin resistance on the dynamics of bacterial killing and resistance.

Methods

A hollow fibre infection model (HFIM) was used to simulate polymyxin B regimens against an mcr-1 -harbouring Escherichia coli (MIC 8 mg/L) over 10 days. Four escalating polymyxin B 'front-loading' regimens (3.33, 6.66, 13.3 or 26.6 mg/kg for one dose followed by 1.43 mg/kg every 12 h starting 12 h later) simulating human pharmacokinetics were utilized in the HFIM. A mechanism-based, math

SUBMITTER: Smith NM 

PROVIDER: S-EPMC5890756 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature