Resistance to Cefamandole: Derepression of -Lactamases by Cefoxitin and Mutation in Enterobacter cloacae

Abstract

Studies were performed to characterize resistance to cefamandole in two strains of Enterobacter cloacae. Susceptible wild-type cells were exposed either to cefamandole to select stably resistant mutants or to cefoxitin to induce unstable resistance. The two types of resistant cells inactivated cefamandole, and their β-lactamases had identical isoelectric focusing patterns and substrate profiles. Studies of the β-lactamases of these resistant cells indicated that the enzymes belonged to the Richmond and Sykes Group I and suggested that their production in wild-type cells is under repressor control. The resistant mutants appeared to be stably derepressed at the locus for β-lactamase expression, whereas cefoxitin-induced cells were reversibly derepressed wild-type cells. Transfer of plasmids from one mutant colony to recipient Escherichia coli cells did not transfer resistance. These two types of resistance to cefamandole may explain the widely discrepant results obtained during in vitro and in vivo studies, as well as the rapid emergence of resistance that has been observed during clinical use.