FIG 4.
In vivo dose effect of ACT-292706 against select S. pneumoniae (A) and S. aureus (B) isolates in a neutropenic mouse thigh model. Each symbol represents the result of the mean of data for three animals (six thighs). Five or six total drug dose levels were fractionated into an every-3-h regimen. ACT exposure is expressed as the free-drug 24-h AUC/MIC ratio. The burden of organisms was measured at the start and end of therapy. The study period was 24 h. The horizontal dashed line at zero represents the burden of organisms in the thighs of mice at the start of therapy. Data points below the line represent killing, and points above the line represent growth. The R2 value represents the coefficient of determination. The line drawn through the data points is the best-fit line based upon the sigmoid Emax (maximum effect) formula. ED50, 50% maximal effect; N, slope of the best-fit line.