Lack of correlation between beta-lactamase production and susceptibility to cefamandole or cefoxitin among spontaneous mutants of Enterobacteriaceae.

A large number of cultures of gram-negative bacteria were examined for their susceptibility to various concentrations of cefamandole, cefoxitin, carbenicillin, and nalidixic acid. Heterogeneity of susceptibility was demonstrated in individual cultures to all of these antibiotics. Resistant clones isolated from cefamandole or cefoxitin plates were examined for beta-lactamase production. Approximately 13% of 262 resistant clones acquired the ability to produce a beta-lactamase. Examination of the substrate profile of the beta-lactamases from some of these clones revealed no change in the specific activity of these enzymes for cefamandole, cephaloridine, or compound 87/312 as compared with their parental enzymes. This study clearly shows that some resistant clones do not produce beta-lactamases, whereas some susceptible strains produced significant amounts of these enzymes. We conclude from these findings that little correlation exists between beta-lactamase production and decreased susceptibility to cefamandole or cefoxitin. The results suggest the possibility that characteristics other than beta-lactamase production may be responsible for resistance in Enterobacteriaceae.