FIG 4.

Dose fractionation study of cefepime in combination with enmetazobactam against Klebsiella pneumoniae. In panel A, the data from vehicle-treated controls (solid black squares) are shown, and these data were overlaid with the data from a cohort of mice receiving 100 mg/kg cefepime q8h i.v. (solid red squares) obtained from the same experiment. Mice shown in panels B to D all received 100 mg/kg cefepime q8h i.v. and a total daily dosage of 15 mg/kg/day enmetazobactam. Enmetazobactam was administered as 7.5 mg/kg q12h (B), 5 mg/kg q8h (C), and 2.5 mg/kg q4h (D). The fit of a PK-PD model to the data is shown, with the plasma concentrations and bacterial density represented by the red and black solid lines, respectively. The PK was used in the fitting but was not specifically measured in this experiment. The pharmacodynamic data (solid black squares) are means ± standard deviations from n = 4 mice.