Colistin and doripenem combinations against Pseudomonas aeruginosa: profiling the time course of synergistic killing and prevention of resistance.

ABSTRACT:

Objectives

Colistin is an 'old' drug, which is being increasingly utilized due to limited therapeutic options. However, resistance emergence during monotherapy is concerning. Here, our objective was to optimize colistin combinations against Pseudomonas aeruginosa by profiling the time course of synergistic killing and prevention of resistance.

Methods

Hollow-fibre infection models over 10 days simulated clinically relevant dosage regimens of colistin and doripenem against two heteroresistant P. aeruginosa strains (MIC 1 mg/L) and one resistant (MIC 128 mg/L) strain (inoculum 10(9.3) cfu/mL). New mathematical mechanism-based models (MBMs) were developed using S-ADAPT.

Results

Against heteroresistant P. aeruginosa strains, colistin monotherapy resulted in initial killin

SUBMITTER: Ly NS 

PROVIDER: S-EPMC4398476 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature