β-LACTAMASES IN LABORATORY AND THEIR ROLE IN RESISTANCE PART I.: Evolution of bacterial resistance mediated by β-lactamases

Autori:

BRANKA BEDENIĆ

Sažetak
β-laktamaze su najčešći uzrok bakterijske rezistencije na β-laktamske antibiotike. One se fenotipski klasificiraju na temelju izoelektrične točke, supstratnog profila, osjetljivosti na inhibitore i genetskog podrijetla. Kromosomske β-laktamaze tipične su za pojedine bakterijske vrste, dok su plazmidne prenosive između različitih vrsta i rodova. Određivanjem sekvencije β-laktamaza gena možemo te enzime podijeliti u 4 razreda: A, B, C i D. Sposobnost β-laktamaza da izazovu rezistenciju ovisi o lokalizaciji, kinetici i količini enzima, kao i o fizikalno-kemijskim uvjetima. Prve β-laktamaze opisane su kod stafilokoka vrlo brzo nakon uvođenja penicilina. Plazmidne β-laktamaze širokog spektra pojavile su se sredinom 60-ih godina prošlog stoljeća a razgrađuju peniciline i neke cefalosporine prve generacije. U tu skupinu spadaju TEM-1, TEM-2, SHV-1, ROB, BRO, OXA i PSE β-laktamaze. Prenose se konjugacijom među različitim vrstama i sojevima gram-negativnih bakterija. Noviji β-laktamski antibiotici danas su ugroženi pojavom β-laktamaza proširenog spektra (ESBL), inhibitor-rezistentnih β-laktamaza i karbapenemaza. β-laktamaze proširenog spektra pojavile su se prije 20 godina, a nastale su mutacijama od parentalnih TEM i SHV-1 β-laktamaza, koje mijenjaju konfiguraciju aktivnog središta i šire spektar njihove aktivnosti. Hidroliziraju oksiminocefalosporine i aztreonam. Njihova brza i točna laboratorijska detekcija važna je za pravilan odabir terapije. Terapijske mogućnosti za liječenje infekcija uzrokovanih enterobakterijama koje proizvode β-laktamaze proširenog spektra ograničene su zbog multiple rezistencije koja uključuje i ne-β-laktamske antibiotike. Karbapenemi su zasada antibiotici izbora za liječenje takvih infekcija.
Summary

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.

Volumen: 11-12, 2004

Liječ Vjesn 2004;126:314–324

Branka Bedenić

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