FIG 2.

Dose fractionation study to determine PK/PD index linked to ertapenem efficacy. The concentration time profiles are shown relative to the MIC. Symbols indicate measured concentrations and the lines modeled profile. (A) Concentration-time profiles of ertapenem identified in the HFS-TB with a dosing schedule of every 8 h. (B) Concentration-time profiles of ertapenem identified in the HFS-TB with a dosing schedule of every 12 h. (C) Concentration-time profiles of ertapenem identified in the HFS-TB with a dosing schedule of once a day. Given the concentration range, the scale obscures the time that concentrations persisted above MIC for some doses. For the blue open circles, the lowest concentration, the time above MIC was 0 h. For the dose shown by cayenne triangles the time was 3 h, for the black open diamonds it was 8.32 h, and for the open magenta squares it was 11.7 h. The rest can be read off the graph. (D) Inhibitory sigmoid E_max model for %T_MIC versus bacterial burden. On day 7, the maximal kill (E_max) was 1.14 log₁₀ CFU/ml, consistent with findings in the first HFS-TB dose-effect study. The study was carried out for only 14 days. Examination of the curves on each day shows that 80% of maximal kill occurs around a %T_MIC of 40% on all sampling days except day 3, when it occurs with lower exposures.