FIG 2.

In vivo efficacy and pharmacokinetic of POL7001 against P. aeruginosa RP73 in a mouse model of acute airway infection.(A) C57BL/6 male mice (8 to 10 weeks of age) were infected i.t. with 1 × 10⁷ CFU of planktonic MDR-RP73. After MDR-RP73 infection, 8 mg/kg CIP or 2 mg/kg POL7001 or saline solution was administered via the i.t. route. Mouse lungs were collected after 4, 8, or 24 h, homogenized, and plated on tryptic soy agar (TSA) plates to determine the bacterial load. (B) The concentration of POL7001 at 4, 8, or 24 h postdosing was measured in lung tissue and plasma of infected mice. Data represent mean values ± standard errors of the means (SEM). (C) The concentration of POL7001 at 24, 48, or 72 h after 2 mg/kg i.t. dosing was measured in lung tissue and plasma of healthy (noninfected) C57BL/6 male mice (8 to 10 weeks of age). Data represent mean values ± standard errors of the means (SEM). The concentration of POL7001 in plasma was below the lowest limit of quantification (LLQ) of 5 ng/ml at the 3 time points. (D) BALF was recovered from C57BL/6 male mice (8 to 10 weeks of age) 24 h after i.t. infection with 1 × 10⁷ CFU of planktonic MDR-RP73 and treatment with 8 mg/kg CIP or 2 mg/kg POL7001 or saline solution administered by the i.t. route. Counts of total number of cells, neutrophils, and macrophages were performed. The data are pooled from two or three independent experiments (n = 8 to 16). Statistical significance determined by the Mann-Whitney U test or one-way ANOVA followed by Dunnett's analysis is indicated as follows: *, P < 0.05; **, P < 0.01; ***, P < 0.001.