Optimization of Synergistic Combination Regimens against Carbapenem- and Aminoglycoside-Resistant Clinical Pseudomonas aeruginosa Isolates via Mechanism-Based Pharmacokinetic/Pharmacodynamic Modeling.

ABSTRACT: Optimizing antibiotic combinations is promising to combat multidrug-resistant Pseudomonas aeruginosa This study aimed to systematically evaluate synergistic bacterial killing and prevention of resistance by carbapenem and aminoglycoside combinations and to rationally optimize combination dosage regimens via a mechanism-based mathematical model (MBM). We studied monotherapies and combinations of imipenem with tobramycin or amikacin against three difficult-to-treat double-resistant clinical P. aeruginosa isolates. Viable-count profiles of total and resistant populations were quantified in 48-h static-concentration time-kill studies (inoculum, 10^7.5 CFU/ml). We rationally optimized combination dosage regimens via MBM and Monte Carlo simulations against isolate FADDI-PA088 (MIC of i

SUBMITTER: Yadav R 

PROVIDER: S-EPMC5192108 | biostudies-literature | 2017 Jan

REPOSITORIES: biostudies-literature