betalaktamase

Beta-lactamases are enzymes produced by bacteria that hydrolyze beta-lactam antibiotics, rendering them ineffective. By breaking the beta-lactam ring, these enzymes prevent the antibiotic from inhibiting bacterial cell-wall synthesis. They can inactivate penicillins, cephalosporins, monobactams, and in some cases carbapenems, contributing to prominent antibiotic resistance.

The Ambler classification groups beta-lactamases into four classes (A through D) based on amino acid sequences. Classes A, C, and D are serine beta-lactamases that use an active-site serine to hydrolyze substrates. Class B comprises metallo-beta-lactamases, which require zinc and employ a metal-dependent mechanism. Clinically significant subgroups include extended-spectrum beta-lactamases (ESBLs), AmpC beta-lactamases, and carbapenemases such as KPC, NDM, VIM, IMP, and OXA-48.

Resistance spread is often plasmid-mediated, enabling rapid transfer of beta-lactamase genes between bacteria, though chromosomal genes also exist. ESBLs and carbapenemases have reduced treatment options, driving reliance on non-beta-lactam antibiotics or newer inhibitor combinations. Detection methods include phenotypic tests (for example, nitrocefin-based assays) and molecular assays that identify specific beta-lactamase genes.

Treatment and management rely on beta-lactamase inhibitors that restore activity of certain beta-lactams. Serine enzyme inhibitors such as clavulanate, tazobactam, and sulbactam are used in combination therapies, while newer inhibitors like avibactam, relebactam, and vaborbactam expand coverage against many resistant enzymes. Metallo-beta-lactamases pose greater therapeutic challenges and may require non-beta-lactam agents or combination strategies. Ongoing surveillance, antibiotic stewardship, and infection-control measures are essential to limit the spread of beta-lactamase-mediated resistance.