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 beta-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 beta-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 (derepressed) overproducers of large amounts of AmpC molecules. As a consequence, such cells acquire a stable resistance to beta-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.