DIFFERENCES IN THERAPEUTIC EFFICACY AMONG CELL WALL-ACTIVE ANTIBIOTICS IN A MOUSE MODEL OF GRAM-NEGATIVE SEPSIS

The in vivo efficacy of three cell wall-active antibiotics, imipenem, meropenem, and ceftazidime, was compared in mice rendered hypersuscept ible to the pathophysiologic effects of lipopolysaccharide by treatmen t with D-galactosamine. When CF-1 mice were administered Escherichia c oli, D-galactosamine, and saline intraperitoneally, an LD(50) was achi eved at an inoculum of similar to 2 x 10(4) cfu. Administration of ant ibiotic at 20 mg/kg resulted in significant but widely variable protec tive efficacy from E. coli lethality among the three antibiotics. At t his dose, an similar to 3-fold increase in LD(50) was observed with ei ther meropenem or ceftazidime, whereas administration of imipenem resu lted in an similar to 8-fold increase in LD(50) (P = .0053). When the dose of antibiotic was decreased to 2 mg/kg, neither meropenem nor cef tazidime could provide measurable protection, whereas imipenem was alm ost fully protective (P < .002). These differences in protective effic acy were also noted with experimental Pseudomonas aeruginosa but not S taphylococcus aureus infection.