Multi-scale model of drug induced adaptive resistance of Gram-negative bacteria to polymyxin B.

ABSTRACT: The purpose of this report is to apply multi-scale modeling using the theory of physiologically structured populations (PSP) to develop a mathematical model for antimicrobial resistance based on a heterogeneous distribution of receptors and affinities among bacterial cells. The theory has been tested on data obtained from an in vitro static time-kill infection model analyzing the pharmacodynamics of polymyxin B against Gram-negative bacteria. The drug binding parameter KD (dissociation equilibrium constant) is assumed to vary between the bacterial cells. The PSP model describes the time course of the density distribution of KD upon exposure to cytotoxic drug concentrations. The drug increases the hazard of cell death as a function of receptor occupancy. The initial distribution of KD is de

SUBMITTER: Krzyzanski W 

PROVIDER: S-EPMC5363806 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature