Population analysis of susceptibility to cefotaxime in Enterobacteriaceae

Population analysis of susceptibility to cefotaxime (CTX) in eight species of Enterobacteriaceae was carried out. One strain of each species was examined. The strains represented their individual species as regards natural susceptibility to ampicillin (A) and carbenicillin (Ca). Cephalothinase activity of the parental strains and strains selected on the plates with the highest concentration that allowed growth was determined by an ultraviolet assay. The populations of the A-susceptible/Ca-susceptible (A-s/Ca-s) species, Escherichia coli and Proteus mirabilis were homogeneous as regards susceptibility to CTX. The A-resistant/Ca-resistant (A-r/Ca-r) species, Klebsiella oxytoca and Citrobacter koseri, were less homogeneous, but in all four mentioned species no increase in cephalothinase activity was observed between the parental strains and the strains selected in the population analysis. The four A-r/Ca-s species, Enterobacter cloacae, Citrobacter freundii, Proteus vulgaris, and Morganella morganii, were heterogeneous. The frequency of CTX-r mutants was approx. 10(-6.5). The IC50 for CTX was 2(7.5)-2(8.5) times higher for the mutants than for the parental strains. The CTX resistance was maintained in subcultures of the strains. All four species had a very high increase in cephalothinase activity from parental strains to the strains selected in the population analysis. Only the enzyme of Proteus vulgaris was able to hydrolyze CTX.