Betalactamases

Beta-lactamases, sometimes spelled betalactamases, are enzymes produced by many bacteria that hydrolyze the beta-lactam ring of beta-lactam antibiotics, rendering the drug ineffective. By breaking the core structure shared by penicillins, cephalosporins, monobactams, and carbapenems, these enzymes are a principal mechanism of antibiotic resistance in both Gram-positive and Gram-negative pathogens. The genes encoding beta-lactamases are carried on chromosomes, plasmids, or transposons, enabling spread within and between species.

Beta-lactamases are classified by substrate spectrum and molecular structure. The Ambler classification divides them into four classes: A, C and D are serine beta-lactamases, which use a serine residue in their active site; class B enzymes are metallo-beta-lactamases requiring divalent metal ions (usually zinc) for activity. Clinically important groups include extended-spectrum beta-lactamases (ESBLs), which hydrolyze third-generation cephalosporins and are often plasmid-mediated (common families TEM, SHV, CTX-M); AmpC beta-lactamases, which hydrolyze cephalosporins and cephamycins and can be inducible or plasmid-encoded; and carbapenemases, which degrade carbapenems and include KPC (class A), NDM, VIM, IMP (class B), and OXA-type enzymes (class D).

Detection and treatment are guided by susceptibility testing and surveillance. Inhibitors such as clavulanic acid, tazobactam, avibactam, and vaborbactam extend activity against many beta-lactamases, but metallo-beta-lactamases are resistant to many of these inhibitors. Combination therapies and non-beta-lactam antibiotics are used to manage infections caused by beta-lactamase–producing organisms.