Fig. 3

Administration of EB211 and EB279 prevented severe tissue damage in the kidneys of immunocompromised mice with A. baumannii pneumonia. Immunocompromised mice were inoculated intranasally with XDR A. baumannii A.b.56 at a 50% lethal dose (LD₅₀; 4×10⁷ CFU per mouse). Immunocompromised infected mice were administered intraperitoneally twice daily with EB211 (12 mg/kg), EB279 (12 mg/kg), a cocktail of the two scFvs (CKT; 6 mg/kg of each), an irrelevant scFv (MEH158; an S. aureus-specific scFv) (12 mg/kg), colistimethate sodium (CMS; 30 mg/kg), or normal saline (NS), or once daily with EB211 (12 mg/kg) (Q24H) two hours after inoculation for 72 h. Healthy (H), immunocompromised uninfected (IU), and immunocompromised infected (Iinf) mice were killed at 72 h of infection, and the kidneys were collected. Tissue sections were stained with hematoxylin-eosin and microscopically evaluated for histopathological alterations. Tubular degeneration and necrosis, and infiltration of inflammatory cells (leukocytes) into the interstitial tissue surrounding the tubules in the cortex and medulla were the marked pathological symptoms in Iinf mice treated twice daily with NS, MEH158, or CMS, or once daily with EB211 (Q24H). After 72 h of infection, no severe pathological signs were detected in the kidneys of Iinf mice treated twice daily with EB211, EB279, or CKT for 72 h. Black arrowheads: tubular necrosis, Green arrows: diminished and distorted glomeruli, White arrows: infiltration of inflammatory cells (leukocytes), White arrowheads: cytoplasmic vacuolation and pale-staining plus fragmented cytoplasm