Ceftazidime/avibactam: a potent arsenal against multidrug-resistant Pseudomonas aeruginosa-unveiling in vitro and in vivo strategies.

BACKGROUND

Ceftazidime/avibactam (CZA) is recognized as an efficacious treatment modality against multidrug-resistant Pseudomonas aeruginosa. Nevertheless, it encounters the challenge of escalating antimicrobial resistance. Employing combination regimens involving ceftazidime/avibactam may confer advantages.

METHODS

Checkerboard titration, time-kill assays, and an in vitro pharmacodynamic model were employed to investigate the effectiveness of ceftazidime/avibactam alone and in combination in vitro. Additionally, an intraperitoneal infection mouse model was established to assess the efficacy of combination therapy in vivo.

RESULTS

In the in vitro pharmacodynamic model, administration of ceftazidime/avibactam plus polymyxin B resulted in a significant reduction in colony-forming units of all four strains, whereas ceftazidime/avibactam plus aztreonam only reduced the colonies of three strains. Significant or trending declines in mortality and tissue colony counts of infected mice were observed in groups treated with ceftazidime/avibactam plus polymyxin B. Conversely, ceftazidime/avibactam combined with aztreonam only reduced mortality and tissue colonies in MBL-positive P.aeruginosa-infected mice.

CONCLUSION

Combining ceftazidime/avibactam with polymyxin B might represent a potentially effective option against MDR-P.aeruginosa. Although the synergistic effect in vitro might not be readily apparent due to the potent bactericidal effect of aztreonam alone, the combination of ceftazidime/avibactam and aztreonam demonstrated promising synergistic effects on MBL-positive P.aeruginosa strains in vivo.