Microdialysis Study of Aztreonam-Avibactam Distribution in Peritoneal Fluid and Muscle of Rats with or without Experimental Peritonitis [PublishAheadOfPrint]

The purpose of this study was to investigate aztreonam (ATM) and avibactam (AVI) distribution in intraperitoneal fluid and muscle interstitial fluid by microdialysis in rats, with or without peritonitis, and to compare the unbound concentrations in tissue with the unbound concentrations in blood. Microdialysis probes were inserted into the jugular vein, hind leg muscle and peritoneal cavity of control rats (n = 5) and rats with intra-abdominal sepsis (n = 9) induced by cecal ligation and punctures. ATM and AVI probe recoveries in each media were determined for both molecules in each rat by retrodialysis by drug. ATM-AVI combination was administered as an intravenous (IV) bolus at a dose of 100-25 mg⋅kg^-1. Microdialysis samples were collected over 120 min, and ATM-AVI concentrations were determined by LC-MS/MS. Non-compartmental pharmacokinetic analysis was conducted and non-parametric test were used for statistical comparisons between groups (infected versus control) and medium. ATM and AVI distribution in intraperitoneal fluid and muscle was rapid and complete both in control rats and in rats with peritonitis and concentration profiles in blood, intraperitoneal fluid and muscle were virtually superimposed, in control and infected animals, both for ATM and AVI. No statistically significant difference was observed between unbound tissue extracellular fluid (ECF) and systemic areas under the curve for both molecules in control and infected animals. In the present study, intraperitoneal infection induced by cecal ligation and puncture had no apparent effect on ATM and AVI pharmacokinetics in rats.

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