Relation of β-Lactamase Activity and Cellular Location to Resistance of Enterobacter to Penicillins and Cephalosporins

The Enterobacter species E. aerogenes, E. cloacae, and E. hafnia were examined for resistance to penicillin and cephalosporin derivatives. All were resistant to benzyl penicillin, ampicillin, 6 [d(-)alpha-amino-p-hydroxyphenylacetamido] penicillanic acid, cephaloridine, cephalothin, and cephalexin. A significant number were sensitive to carbenicillin and 6 [d(-)alpha-carboxy-3-thienylacetamido] penicillanic acid. No differences among the three species were noted. The beta-lactamase activity was cell-bound, and was not released by osmotic shock, toluene treatment, or diphenylamine treatment. It was rarely released into the growth medium. The beta-lactamase activity was primarily directed against cephalosporin derivatives. Synthesis of beta-lactamase was chromosomally mediated. Resistance to ampicillin seemed to be partly related to entry of the molecule into the bacteria since exposure to ethylenediaminetetraacetate lowered the minimal inhibitory concentration.