Antimicrobial resistance continues to pose a critical threat to global health, particularly with the rise of metallo-β-lactamase (MBL)-producing Gram-negative bacteria. In this study, we explore the efficacy of aztreonam-avibactam (AZT-AVI) against a multidrug-resistant Escherichia coli strain using the hollow fibre infection model (HFIM). Our findings demonstrate that a clinically relevant AZT-AVI regimen achieves pharmacokinetic/pharmacodynamic targets, exhibits rapid bactericidal activity, and effectively suppresses resistance emergence. This work supports the potential of AZT-AVI as a promising therapeutic option for treating infections caused by MBL-producing Enterobacterales.