Aminoglycoside Concentrations Required for Synergy with Carbapenems against Pseudomonas aeruginosa Determined via Mechanistic Studies and Modeling.

ABSTRACT: This study aimed to systematically identify the aminoglycoside concentrations required for synergy with a carbapenem and characterize the permeabilizing effect of aminoglycosides on the outer membrane of Pseudomonas aeruginosa Monotherapies and combinations of four aminoglycosides and three carbapenems were studied for activity against P. aeruginosa strain AH298-GFP in 48-h static-concentration time-kill studies (SCTK) (inoculum: 107.6 CFU/ml). The outer membrane-permeabilizing effect of tobramycin alone and in combination with imipenem was characterized via electron microscopy, confocal imaging, and the nitrocefin assay. A mechanism-based model (MBM) was developed to simultaneously describe the time course of bacterial killing and prevention of regrowth by imipenem combined with each of t

SUBMITTER: Yadav R 

PROVIDER: S-EPMC5700360 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature