Carbapenemase

Carbapenemases are a diverse group of beta-lactamase enzymes produced by certain bacteria, notably Enterobacteriaceae, that catalyze the hydrolysis of carbapenem antibiotics (StatPearls, NBK554451). These antibiotics are typically reserved as last-line treatments for multidrug-resistant infections, making the presence of carbapenemases a critical clinical challenge (CDC, Carbapenem-resistant Enterobacterales). The enzymes are classified into Ambler classes based on their catalytic mechanism: Class A (serine-based, e.g., KPC), Class B (zinc-dependent metallo-beta-lactamases, e.g., NDM), and Class D (oxacillinases, e.g., OXA-48) (Clinical Microbiology Reviews, doi:10.1128/CMR.00001-07). Carbapenemase-producing Enterobacteriaceae (CPE) infections are associated with high morbidity and mortality due to the lack of effective therapeutic options (Nature Reviews Microbiology, doi:10.1038/nrmicro.2017.131). Modern drug development focuses on beta-lactamase inhibitors, such as avibactam and vaborbactam, which bind to the enzyme's active site and prevent it from degrading co-administered antibiotics (NIH, PMC6627445). While these inhibitors have improved outcomes for serine-carbapenemase infections, the emergence of metallo-beta-lactamases remains a significant gap in current therapy (Frontiers in Microbiology, doi:10.3389/fmicb.2020.00928). Additionally, the rapid evolution of these enzymes leads to new variants that can evade even the newest inhibitors, necessitating ongoing research into novel antimicrobial strategies (Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkz456).

Other names

Beta-lactamaseCarbapenem-hydrolyzing enzymeClass A carbapenemaseMetallo-beta-lactamaseClass D carbapenemaseKPCNDMOXA-48VIMIMP

Inhibition of the carbapenemase enzyme's active site (either through covalent binding to a serine residue or chelation/binding of zinc ions in metallo-beta-lactamases) to prevent the hydrolysis of beta-lactam antibiotics (StatPearls, NBK554451; NIH, PMC6627445).