Selection during cefepime treatment of a new cephalosporinase variant with extended-spectrum resistance to cefepime in an Enterobacter aerogenes clinical isolate

Abstract

Enterobacter aerogenes resistant to cefepime (MIC, 32 microg/ml) was isolated from a patient treated with cefepime for an infection caused by a strain of E. aerogenes overproducing its AmpC beta-lactamase (MIC of cefepime, 0.5 microg/ml). The AmpC beta-lactamase of the resistant strain had an L-293-P amino acid substitution and a high k(cat)/K(m) ratio for cefepime. Both of these modifications were necessary for resistance to cefepime.

FIG. 1.

Multiple amino acid sequence alignment of the AmpC β-lactamases of the following strains: 1, E. aerogenes 97B (accession no. AF211348); 2, E. aerogenes EarCOL; 3, E. aerogenes Ear1; 4, E. aerogenes Ear2. Dashes indicate identical amino acids. Conserved residues of class C β-lactamases are underlined. The amino acid substitution in the Ear2 sequence is shown in boldface. Amino acids are numbered in accordance with the conventional numbering of E. cloacae P99, with the active-site serine at position 64.