Revisiting the Metallo‐ β ‐Lactamase–Mediated Antibiotic Resistance: Exploring Novel Mechanisms and Therapeutic Strategies

β ‐Lactam resistance is one of the major health concerns today, primarily due to enzymes called β ‐lactamases. Metallo‐ β ‐lactamases (M β Ls) can cleave a wide range of β ‐lactam antibiotics, including carbapenems. These enzymes require zinc (Zn) ions to function and can be inhibited by conventional β ‐lactamase inhibitors. According to their structural and functional characteristics, M β Ls are categorized into three classes known as B1, B2, and B3, each with distinct substrate preferences and resistance mechanisms. The prevalence of acquired M β Ls, such as IMP, VIM, and NDM, demonstrates the necessity for the development of effective treatments. Novel therapeutic approaches have emerged as potential treatment options. However, antibiotic toxicity, resistance development, and coexisting resistance mechanisms, such as efflux pumps and porin modifications, complicate treatment strategies. Recent advances in diagnostics have significantly improved the rapid identification of M β L‐producing bacteria, suggesting the selection of treatment and antimicrobial stewardship. This review highlights the urgent need for global efforts to combat M β L‐mediated resistance through surveillance, advanced diagnostics, and innovative therapies, emphasizing the role of advanced and innovative theragnostic approaches in managing M β L infections.