BETA-LACTAMASES AND THEIR ROLE IN RESISTANCE PART 2: Beta-lactamases in 21st century

Autori:

BRANKA BEDENIĆ

Sažetak
Rezistencija na -laktamske antibiotike sve se više povećava, najviše zbog produkcije različitih -laktamaza. Zbog mogućnosti da plazmidi akviriraju različite determinante rezistencije, sve više bolničkih bakterijskih izolata postaje rezistentno na velik broj različitih antibiotika. Najvažnije -laktamaze koje ugrožavaju upotrebu -laktamskih antibiotika u današnje su vrijeme -laktamaze proširenog spektra, inhibitor-rezistentne TEM i SHV--laktamaze i karbapenemaze. Karbapenemaze su-laktamaze koje hidroliziraju karbapeneme. Svrstane su u molekularne grupe A, B i C. Grupa A obuhvaća karbapenemaze osjetljive na inhibiciju klavulanskom kiselinom. Većina je kodirana kromosomski, ali neke od njih su i plazmidne kao KPC u Klebsiella pneumoniae i GES-2 u Pseudomonas aeruginosa. U grupi B su metalo--laktamaze iz IMP i VIM-serije. Karbapenemaze iz grupe D su najčešće u Acinetobacter baumannii, a uzrokuju rezistenciju na karbapeneme ako postoje i drugi mehanizmi rezistencije kao npr. promjene u porinima. Inhibitor-rezistentne -laktamaze jedan su od najvažnijih uzroka rezistencije na -laktam-inhibitorske kombinacije. Rezistencija na takve formulacije može biti također uzrokovana hiperprodukcijom TEM1--laktamaze, modifikacijama proteina vanjske membrane ili produkcijom OXA--laktamaza. IRT-enzimi nastaju od parentalnih TEM-1 i TEM-2--laktamaza točkastim mutacijama u -laktamaznome genu. Česta primjena -laktamaznih inhibitora u bolnicama i u općoj medicini selekcionira sojeve s takvim mutacijama u hospitalnoj i izvanbolničkoj sredini.
Summary

Summary. Resistance to β-lactam antibiotics continues to increase, mostly due to the presence of various β-lakta mases. As a result of the ability of the plasmids to acquire additional resistance determinants, many of the β-lactamase producing pathogens became multidrug resistant.The most important β-lactamases which compomise the use of β-lactams nowdays are extended- spectrum β-lactamases, inhibitor-resistant TEM and SHV β-lactamases and carbapenemases. Carbapenemases are β-lactamases which hydrolyse carbapenems. They belong to molecular classes A, B, and D. Class A comprises carbapenemases sensitive to inhibition by clavulanic acid. Most of them are chromosomaly encoded, but some of them are plasmid-mediated such as KPC-1 in Klebsiella pneumoniae and GES-2 in Pseudomonas aeruginosa. The class B carbapenemases are metallo-β-lactamases of the IMP or VIM group. The class D carbapenemases are the most frequent in Acinetobacter baumannii but confer resistance to carbapenems only if other resistance mechanisms such as porin alterations, are present. Inhibitor resistant β-lactamases are one of the most important causes of resistance to β-lactam-inhibitor combinations. The resistance to these formulations can be also due to hyperproduction of TEM-1 β-lactamase, modifications of the outer membrane proteins or production of OXA-type enzymes. IRT enzymes are derived from parenthal TEM-1 or TEM-2 β-lactamases by point mutations in the β-lactamase gene. The frequent use of β-lactamase inhibitors in hospitals and general practice pose a selection pressure which favours spread of such strains in hospitals and community.

Volumen: 1-2, 2005

Liječ Vjesn 2005;127:12–21

Branka Bedenić

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