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