Pharmacodynamic modelling of β-lactam/β-lactamase inhibitor checkerboard data: illustration with aztreonam–avibactam

Alexia Chauzy, Julien M. Buyck, Boudewijn L. M. de Jonge, Sandrine Marchand, Nicolas Grégoire, William Couet

Clinical Microbiology and Infection · 2018 · 13 citations · 7 references

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Abstract

OBJECTIVES: Checkerboard experiments followed by fractional inhibitory concentration (FIC) index determinations are commonly used to assess in vitro pharmacodynamic interactions between combined antibiotics, but FIC index cannot be determined in case of antibiotic/non-active compound combinations. The aim of this study was to use a simple modelling approach to quantify the in vitro activity of aztreonam-avibactam, a new β-lactam-β-lactamase inhibitor combination. METHODS: model with a baseline effect parameter. RESULTS: values between 0.00022 and 0.053 mg/L). CONCLUSIONS: model with a baseline effect could quantify maximum avibactam effect and potency among various strains. This simple modelling approach can be used to compare the activity of other combinations of antibiotics with non-antibiotic drugs when FIC index is inappropriate.

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