Extended Data Fig. 10. In vivo efficacy of Debio-1452-NH3 with strains that are less susceptible in cell culture.

a. Acute pneumonia infections initiated in CD-1 mice with A. baumannii M13100 (2.1x10⁸ CFU/mouse, intranasal) were treated with vehicle (8 mice) or FabI inhibitor (8 mice per group) 6.5 and 23 h post-infection (IV, 50 mg/kg), and the bacterial burden was evaluated 48 h post-infection. b. Acute pneumonia infections initiated in CD-1 mice with K. pneumoniae S20595 (1.9x10⁸ CFU/mouse, intranasal) were treated with vehicle (8 mice) or FabI inhibitor (8 mice per group) 6.5 and 22.5 h post-infection (IV, 50 mg/kg), and the bacterial burden was evaluated 48 h post-infection. c. Acute pneumonia infections initiated in CD-1 mice with K. pneumoniae BAA2473 (3.4x10⁸ CFU/mouse, intranasal) were treated with vehicle (8 mice) or FabI inhibitor (8 mice per group) 6 and 22.5 h post-infection (IV, 50 mg/kg), and the bacterial burden was evaluated 48 h post-infection. d. Acute pneumonia infections initiated in CD-1 mice with K. pneumoniae AR0347 (2.5x10⁸ CFU/mouse, intranasal) were treated with vehicle (8 mice) or FabI inhibitor (8 mice per group) 6 and 23 h post-infection (IV, 50 mg/kg), and the bacterial burden was evaluated 48 h post-infection. Drugs were formulated in 20% sulfobutyl ether(7) β-cyclodextrin from solid immediately before treatment. For the bacterial burden studies (a-d), data are shown as mean and error bars represent standard deviation. Significance was determined by one-way analysis of variance (ANOVA) with Tukey’s multiple comparisons. Statistical significance is indicated with asterisks (ns, not significant when p > 0.05 (a, p = 0.8582; b, p = 0.1019; c, p = 0.7600; d, p = 0.7536), **** p < 0.0001). Debio-1452-NH3 has an MIC of 16 μg/mL for all four strains used in these mouse models.