Comprehensive Review on Ceftazidime-Avibactam Resistance: Understanding Mechanisms and Addressing Challenges

Abstract

This review focuses on the resistance to ceftazidime-avibactam (CAZ-AVI), a cephalosporin/β-lactamase inhibitor complex used to treat multidrug-resistant gram-negative bacterial infections. The significance of β-lactam antibiotics and their mechanism of action is discussed, along with the role of β-lactamases and the efficacy of avibactam in restoring ceftazidime's activity. The review highlights the structure and mechanism of action of CAZ-AVI and its approved indications. However, resistance to CAZ-AVI has emerged, posing a significant challenge. The genetic basis and mechanisms of resistance, including enzymatic resistance, alterations in cell membrane permeability, efflux pumps, and unhindered β-lactamases production, are examined. The current epidemiology of CAZ-AVI resistance is summarized, emphasizing the need for surveillance and appropriate infection prevention. The review concludes by discussing alternative treatment options, such as dual carbapenem therapy and combination therapies involving other inhibitors. The potential of aztreonam against metallo-β-lactamase-producing isolates is also explored. Continued research and development of novel therapies and antimicrobial stewardship programs are emphasized. In summary, this review provides insights into CAZ-AVI resistance, its clinical implications, and potential strategies to address this challenge.