Prediction of in vivo and in vitro infection model results using a semimechanistic model of avibactam and aztreonam combination against multidrug resistant organisms.
CPT Pharmacometrics Syst Pharmacol
; 6(3): 197-207, 2017 03.
Article
em En
| MEDLINE
| ID: mdl-28145085
ABSTRACT
The combination of aztreonam-avibactam is active against multidrug-resistant Enterobacteriaceae that express metallo-ß-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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Aztreonam
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Farmacorresistência Bacteriana Múltipla
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Compostos Azabicíclicos
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Modelos Biológicos
Tipo de estudo:
Prognostic_studies
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Risk_factors_studies
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article