Table 3.
S. aureus strain | MIC (μg/ml) |
Mean ED50 (mg/kg/day) in murine systemic infection model |
Murine thigh infection model |
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---|---|---|---|---|---|---|---|---|---|
Mean static MUT056399 dose (mg/kg/day) | Mean bacterial burden reduction (log10)b |
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MUT056399 | Vancomycin | Linezolid | MUT056399 | Vancomycin | Linezolid | MUT056399 | Linezolid | ||
MSSA ATCC 29213 | 0.06 | 1 | 4 | 21.6 | 1.6 | NDc | 40 | 1.5 | 1.4 |
MRSA ATCC 33591 | 0.06 | 2 | 2 | 31.8 | 6.7 | ND | 45.5 | 1 | 0.7 |
MRSA NRS 382 (USA100) | 0.06 | 2 | 2 | 19.3 | 6 | ND | 44 | 1 | 1.1 |
MRSA NRS 384 (USA300) | 0.06 | 1 | 1 | 45.1 | 9.4 | ND | |||
MRSA NRS 385 (USA500) | 0.06 | 1 | 1 | 28.3 | 5 | ND | |||
MRSA/GISA JUS | 0.03 | 4 | 4 | 49.6 | ND | 3.6 |
In the systemic infection model, the ED50 was the dose that allowed the survival of 50% of each group of treated mice at 48 h postinfection in at least two experiments. In the thigh infection model, bacterial recovery in the thighs of infected animals was performed at 20 h postinfection. All calculations were performed using XL-Stat software. P values were determined with the Dunnett test. Mean values of at least two experiments are shown.
The mean bacterial burden reduction in the thigh was measured after a single administration of MUT056399 or linezolid at 50 mg/kg.
ND, not done.