Extended spectrum -lactamases (ESBL) - an emerging threat to clinical therapeutics

Abstract

Extended spectrum -lactamases (ESBLs) are plasmid mediated, TEM and SHV derived enzymes, first isolated in Western Europe in mid 1980s, most commonly in Klebsiella spp., followed by Escherichia coli. These enzymes are capable of hydrolyzing broad spectrum cephalosporins and monobactams but inactive against cephamycins and imipenem. In addition, ESBL producing organisms exhibit coresistance to many other classes of antibiotics resulting in limitation of therapeutic option. Several risk factors have been suggested. A variety of classification schemes have been developed. Recently, Bush-Jacoby-Medeiros scheme integrated functional and molecular characteristics. ESBLs have serine at their active site and attack the amide bond in the lactam ring of antibiotics causing their hydrolysis. Because of inocolum effect and substrate specificity their detection is a major challenge. Two indicators of ESBLs are eight fold reduction in MIC and potentiation of the inhibitor zone of third generation cephalosporin in the presence of clavulanic acid. Incidence of these organisms is being continuously increasing through out the world with limited treatment alternatives. It becomes necessary to know the prevalence of these organisms and to formulate treatment policy. Moreover, restricted use of the third generation cephalosporins lead to withdrawal of selective pressure and use of lactam and -lactamase inhibitor combinations may exert reverse mutation on these enzymes.