The Origin, by Mutation, of High Level Resistance to Ceftazidime and Cefotaxime in a Clinical Isolate of Enterobacter cloacae

Abstract

Although strains of Enterobacter sp. produce a chromosomal AmpC β-lactamase, they have been, in general, susceptible to cefotaxime or ceftazidime. But now resistance to ceftazidime has increased in nosocomial Enterobacter strains, reaching the level of 40%. A chromosomal mutation in the amp operon coding the production of AmpC type β-lactamase may cause a change in the conversion of a susceptible strain of Enterobacter to a highly resistant mutant. The production of AmpC enzyme is inducible and third-generation cephalosporins are weak inducers of AmpC production. Spontaneous mutations (or insertions of transposons) in the regulatory region of amp operon might create constitutive (de-repressed) overproducers of large amounts of AmpC molecules. As a consequence, such cells acquire a stable resistance to β-lactam antibiotics including cefotaxime or ceftazidime. We describe the origin of mutants of a clinical isolate of Enterobacter cloacae that acquired high-level resistance to ceftazidime followed by the resistance to cefotaxime and/or aztreonam due to a second mutation.