Ex vivo pharmacodynamics of 1.1 g IV amoxicillin-clavulanic acid against beta-lactamases (positive) E. coli in a yuctan micropig model that mimics human pharmacokinetics (2.2 g IV)

摘要

Six adult micropigs received a single doses of 1.1 g Augmentin (amoxicillin-clavulanic acid), by 30 min. IV infusion corresponding to 2.2 g human. The pharmacokinetic parameters were calculated, and they were similar to those obtained in human (2.2 g IV). Therefore, the ex vivo pharmacodynamic studies were achieved on E. coli strains producing beta-lactamases at variable levels, and strains were submitted to time-kill experiments. A high bactericidal activity was obtained on the low level penicillinase strain, even when Augmentin concentrations were far below MIC/MBC. For the intermediate and high-level penicillinase strains, time-kill activity showed a high dependence of clavulanic acid concentrations. The index of surviving bacteria as a function of amoxicillion concentration indicate concentration and time dependent activities of amoxicillin (combined with clavulanic acid) according to the production levels of beta-lactamases by the E. coli strains. This work showed a good activity of Augmentin 2.2 g IV against low and intermediate level penicillianse strains, and further investigation on experimental infection in the micropig model must be achieved.