Journal
CPT-PHARMACOMETRICS & SYSTEMS PHARMACOLOGY
Volume 6, Issue 3, Pages 197-207Publisher
WILEY
DOI: 10.1002/psp4.12159
Keywords
-
Categories
Funding
- AstraZeneca
- Forest-Cerexa subsidiary of Allergan
Ask authors/readers for more resources
The combination of aztreonam-avibactam is active against multidrug-resistant Enterobacteriaceae that express metallo--lactamases. A complex synergistic interaction exists between aztreonam and avibactam bactericidal activities that have not been quantitatively explored. A two-state semimechanistic pharmacokinetic/pharmacodynamic (PK/PD) logistic growth model was developed to account for antimicrobial activities in the combination of bacteria-mediated degradation of aztreonam and the inhibition of aztreonam degradation by avibactam. The model predicted that changing regimens of 2 g aztreonam plus 0.375 and 0.6 g avibactam as a 1-hour infusion were qualitatively similar to that observed from in vivo murine thigh infection and hollow-fiber infection models previously reported in the literature with 24-hour log kill 1. The current approach to characterize the effect of avibactam in enhancing aztreonam activity from time-kill study was accomplished by shifting the half-maximal effective concentration (EC50) of aztreonam in increasing avibactam concentration using a nonlinear equation as a function of avibactam concentration, providing a framework for translational predictions.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available