Relationship between the PK/PD indices free-drug Cmax/MIC (top left), AUC/MIC (top right), and time above the MIC (T>MIC) (bottom) and the therapeutic effect for MRX-8. Five total dose levels (0.156 to 40 mg/kg) were fractionated into q12h, q8h, q6h, and q3h dosing regimens and administered to thigh-infected (E. coli ATCC 25922) mice. The change in the burden was assessed over the 24-h treatment duration. Points above the dashed line represent the net increase in the bacterial burden, whereas those below the dashed line represent a net decrease in the bacterial burden. The PK/PD parameters Emax (maximum effect), ED50 (50% maximum effect), N (slope of the best-fit line), and R2 (coefficient of determination) are shown for each PK/PD index.