FIG 5.
Efficacy of ND-421 in combination with oxacillin in the mouse neutropenic thigh infection model. Mice (n = 8 mice/group) were rendered neutropenic by intraperitoneal administration of cyclophosphamide at 200 mg/kg on day 4 and day 1 prior to infection. The right thigh was infected intramuscularly with 100 μl of 106 CFU/ml of MRSA NRS70. Mice were given two oral doses of ND-421 at 40 mg/kg at 1 and 25 h after infection; six subcutaneous doses of oxacillin at 20 mg/kg at 1, 9, 17, 25, 33, and 41 h after infection; or a combination of ND-421 plus oxacillin. The infected thighs were collected at 48 h after infection and homogenized, and the homogenate was plated, followed by determination of bacterial counts (mean ± standard error of the mean). *, P ≤ 0.05; **, P ≤ 0.01; ***, P ≤ 0.001, as determined by Mann-Whitney U test. The combination of ND-421 with oxacillin showed increased efficacy with a bacterial load significantly lower than that of the single-agent treatment.