β-LACTAMASES IN LABORATORY AND THEIR ROLE IN RESISTANCE PART I.: Evolution of bacterial resistance mediated by β-lactamases
Summary. β-lactamases are the commonest cause of bacterial resistance to β-lactam antibiotics. They have been classified phenotypically by their isoelectric point, substrate profile, susceptibility to inhibitors and genetic origin. Chromosomal β-lacta- mases are typical for certain bacterial species and plasmid β-lactamases are transferable between different species and genera. Sequencing of β-lactamase genes enabled to divide them into four classes: A, B, C and D. The ability of a β-lactamase to confer resistance depends on its location, kinetics, quantity and physicochemical conditions. First β-lactamases were described soon after introduction of penicillin. Plasmid-mediated broad-spectrum β-laktamases appeared in the middle 60-s of the XX century and confer resistance to penicillins and some first generation cephalosporins.They include TEM-1, TEM-2, SHV-1, ROB, BRO, OXA and PSE β-lactamases and are transferred by conjugation between different species and strains of Gram-negative bacteria. The new β-lactam agents nowadays are compromised mostly by extended-spectrum β-lactamases, inhibitor-resistant β-lacta- mases and carbapenemases. Extended-spectrum β-lactamases (ESBLs) were described for the first time 20 years ago and are derived from the parental TEM and SHV-1 β-lactamases by mutations that alter the configuration of the active site to expand their spectrum of activity. They hydrolyse oxymino-cephalosporins and aztreonam. The rapid and accurate laboratory detection of ESBLs is important for choosing appropriate antibiotic therapy. Infections caused by Enterobacteriaceae producing ESBLs pose a therapeutic problem due to multiple antibiotic resistance which includes non-β-lactam antibiotics as well. Carbapenems are the first-line antibiotics for treatment of such infections.