Plasma stability and in vivo efficacy of fabimycin.
(A) Assessment of fabimycin stability in plasma. Data shown as the
mean and standard deviation from two experiments. (B) Acute pneumonia
infections initiated in CD-1 mice with A. baumannii AR-0299 (1.6 × 108 CFUs per mouse intranasally).
Mice were treated with vehicle (8 mice) or FabI inhibitor (8 mice
per group) 4, 23, and 41 h postinfection (50 mg/kg intramuscular)
and the bacterial burden evaluated at 48h postinfection. (C) Neutropenic
mouse thigh infection initiated in CD-1 mice with A. baumannii AR-0299 (1.22 × 106 CFUs per mouse intramuscular
in thigh) were treated with vehicle (8 mice) or FabI inhibitor (8
mice per group) 2, 6, and 11 h postinfection (50 mg/kg intramuscular),
and the bacterial burden was evaluated 26h postinfection. (D) Neutropenic
mouse thigh infection initiated in CD-1 mice with S. aureus USA300 LAC (2.3 × 106 CFU per mouse intramuscular
in thigh) were treated with vehicle (eight mice) or FabI inhibitor
(eight mice per group) 2 and 7 h postinfection (5 mg/kg retro-orbital
IV), and the bacterial burden was evaluated 24 h postinfection. Debio-1452-tosylate
used. FabI inhibitors formulated with 20% SBE-β-CD in H2O. In B, C, and D statistical significance was determined
by one-way ANOVA with Tukey’s multiple comparisons. NS, not
significant. ****P < 0.0001. Error bars represent
standard deviation.