Development of beta-lactam-resistant Enterobacter cloacae in mice

We compared the ability of four newer beta-lactam compounds to produce resistance in an experimental model of Enterobacter cloacae infection. Mice infected intraperitoneally developed resistance depending on antibiotic treatment and the dose given. Percentages of mice in which resistance was observed were as follows: 100% after ceftriaxone (50 mg/kg, two doses); 87% after ceftriaxone (50 mg/kg, one dose); 35% after ceftriaxone (500 mg/kg, one dose); and 21% after carumonam (25 mg/kg, two doses). No resistance occurred after therapy with either BMY 28142 (25 mg/kg, two doses) or Sch 34343 (50 mg/kg, two doses). Heterogeneous resistance to beta-lactams among the cells within a given Enterobacter population accounted for these differences. The minimal concentration inhibiting the growth of the preexisting resistant variants, together with the antibiotic concentrations obtained in the peritoneal fluid, were associated with further emergence of resistance in the mouse treated with this antibiotic.