Efficacies of cefepime, ceftazidime, and imipenem alone or in combination with amikacin in rats with experimental pneumonia due to ceftazidime-susceptible or -resistant Enterobacter cloacae strains

The antibacterial activities of human regimens of cefepime, ceftazidime, an d imipenem alone or in combination with amikacin against an isogenic pair o f Enterobacter cloacae strains (wild type and its corresponding derepressed cephalosporinase mutant) were compared by using our nonlethal model of pne umonia with 180 immunocompetent rats. Compared with untreated animals, all beta-lactam-treated rats, except those inoculated with the mutant isolate a nd receiving ceftazidime, had significantly lower bacterial counts in their lungs 60 h after the onset of therapy. Although the combination of a beta- lactam and amikacin was more bactericidal than each corresponding antimicro bial agent alone, true synergy was noted only with cefepime and imipenem ag ainst the constitutive derepressed strain.