Cefotaximase-Munich beta-lactamase (CTX-M)

CTX-M beta-lactamases are a group of Class A extended-spectrum beta-lactamases (ESBLs) that have become the most prevalent ESBLs worldwide (Cantón et al., 2012, Clinical Microbiology Reviews). These enzymes are primarily produced by Gram-negative bacteria, such as Escherichia coli and Klebsiella pneumoniae, and are characterized by their ability to hydrolyze and confer resistance to third-generation cephalosporins, particularly cefotaxime (D'Andrea et al., 2013, International Journal of Medical Microbiology). The genes encoding these enzymes, known as blaCTX-M, are frequently located on mobile genetic elements like plasmids, which has facilitated their rapid global dissemination across various bacterial species (Bonnet, 2004, Antimicrobial Agents and Chemotherapy). In clinical practice, CTX-M enzymes are major drivers of multidrug resistance in both community-acquired and healthcare-associated infections, including urinary tract infections and sepsis (Pitout & Laupland, 2008, The Lancet Infectious Diseases). To combat this resistance, these enzymes are targeted by beta-lactamase inhibitors such as clavulanic acid, tazobactam, and newer non-beta-lactam agents like avibactam and vaborbactam (Bush & Bradford, 2016, Cold Spring Harbor Perspectives in Medicine). These inhibitors work by binding to the enzyme's active site, thereby protecting co-administered beta-lactam antibiotics from degradation and restoring their therapeutic efficacy.

Other names

CTX-M-type beta-lactamaseExtended-spectrum beta-lactamaseESBLClass A beta-lactamaseSerine beta-lactamase

Beta-lactamase inhibitors act as suicide substrates or reversible inhibitors that bind to the active-site serine residue of the CTX-M enzyme, forming a stable acyl-enzyme intermediate that prevents the enzyme from hydrolyzing co-administered beta-lactam antibiotics (Bush & Bradford, 2016, Cold Spring Harbor Perspectives in Medicine).