Dissociated resistance among cephalosporins

When disks containing cefuroxime (CXM) or HR 756 (756) were placed next to cefoxitin (FOX) on plates inoculated with Enterobacter resistant to FOX, there was marked flattening of the zones of inhibition produced by CXM or 756, but colonies growing near the CXM or 756 disks were found to be fully susceptible to these drugs on retesting. In contrast, when a checkerboard titration with CXM or 756 and FOX was done in broth, organisms growing in the presence of high concentrations of either of the former plus FOX were found to be resistant on retesting. Broth cultures of Enterobacter were found to contain small numbers of mutants which were resistant to and inactivated CXM and 756. Evidence is presented suggesting that the addition of FOX induces similar properties in the whole culture, which then becomes resistant to all of the nine cephalosporins tested and to four of six penicillins tested. Such cultures rapidly reverted to susceptible when FOX was removed or inactivated, and an explanation is offered as to why this did not happen in fluid media.