Carbapenemase and metallo-beta-lactamase (Carbapenemase/MBL)

Carbapenemases and metallo-beta-lactamases (MBLs) are enzymes produced by Gram-negative bacteria, such as Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii, that confer resistance to carbapenems and most other beta-lactam antibiotics (StatPearls, 2023). These enzymes function by hydrolyzing the beta-lactam ring, thereby inactivating the drug before it can reach its target, the penicillin-binding proteins (Nature Reviews Microbiology, 2020). Carbapenemases are classified into Ambler classes: Class A (e.g., KPC) and Class D (e.g., OXA-48) are serine-based, while Class B (MBLs like NDM, VIM, and IMP) are zinc-dependent hydrolases (WHO, 2024). MBLs are particularly challenging because they utilize a zinc-dependent mechanism that is not inhibited by traditional beta-lactamase inhibitors like clavulanic acid or tazobactam (NIH, 2023). Therapeutic strategies involve the use of novel beta-lactamase inhibitors, such as avibactam, vaborbactam, or relebactam, which covalently bind and inactivate serine-carbapenemases, or siderophore cephalosporins like cefiderocol that exploit bacterial iron transport systems to bypass these enzymes (PubMed, 2021). The presence of these enzymes in clinical isolates is a major driver of extensively drug-resistant (XDR) infections, necessitating rapid diagnostic identification and targeted antimicrobial therapy to improve patient outcomes.

Other names

Carbapenemase- and metallo-β-lactamase–producing Enterobacterales and other XDR gram-negative pathogensCarbapenem-resistant EnterobacteralesCRECPEMBL-PEXDR Gram-negative bacteriaCarbapenem-hydrolyzing enzymesAmbler Class A/B/D beta-lactamases

Inhibition of beta-lactamase enzymes to prevent the hydrolysis of co-administered beta-lactam antibiotics, or utilization of siderophore-mediated transport to bypass resistance mechanisms.