FIG. 3.

In vitro-in vivo efficacy correlation for variants of pyrrolidinedione antibiotics in a murine sepsis model with a reduced S. aureus inoculum. Compounds 2, 4, and 5 were dosed at 10 mg/kg i.v. at 30 and 90 min postinfection, and linezolid was given only at 30 min postinfection. The reductions of CFU in the blood, lungs, liver, and peritoneum determined 5 h after infection were plotted for the different derivatives (see Materials and Methods). Compound 5 (given twice) approximately reached the efficacy of linezolid (administered once). The in vivo efficacy ranking of pyrrolidinediones reflects the improvements of in vitro MIC data, as shown below the diagram.