[Resistance to the latest beta-lactams: mechanisms of acquisition and spread of resistance in Enterobacteriaceae]

Abstract

Resistance to antibiotics may drastically diminish the efficacy of therapy in some clinical circumstances. The emergence of Enterobacteriaceae (Klebsiella pneumoniae, Aerobacter aerogenes, Escherichia coli) resistant to the more recent beta-lactam agents (cefepime, cefpirome, azthreonam and carbapenems) generally results from misuse of antibiotics, leading to the selection of preexisting resistant mutants. Resistance is usually due to beta-lactamase expression, through: -- mutations involving the beta-lactamase structure (TEM, SHV, OXA, CTX-M beta-lactamase families) and/or mutations of beta-lactamase synthesis regulators (AmpC beta-lactamases); or -- the appearance of new enzymes (PER, VEB, CMY, DHA-1, ACC-1, etc.). The level of resistance (particularly to carbapenems) is increased when porin mutations are associated with beta-lactamase expression. The spread of these new resistance mechanisms is amplified by mobilisation of resistance genes from the chromosome to a plasmid (SHV, CTX-M, CMY DHA-1 beta-lactamases genes) and by the location of these genes in mobile elements (integrons and transposons). The recent appearance of these mechanisms (particularly CTX-M beta-lactamases) in strains circulating in the community is a matter of concern.