Fig. 5

Administration of EB211 and EB279 prevented severe tissue damage in the lungs of immunocompromised mice with A. baumannii pneumonia. Immunocompromised mice were inoculated intranasally with XDR A. baumannii A.b.56 at a 50% lethal dose (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. (A) and (B) Healthy (H), immunocompromised uninfected (IU), and immunocompromised infected (Iinf) mice were killed at 72 h of infection, and the lungs were collected. Tissue sections were stained with hematoxylin-eosin and microscopically evaluated for histopathological alterations. Bacterial communities in perivascular areas, infiltration of inflammatory cells (neutrophils and mononuclear cells) in the perivascular and peribronchial areas, parenchymal necrosis, necrosis of bronchial epithelial cells, edema of perivascular spaces, and hemorrhage in the alveoli and interstitium were detected in the lungs of Iinf mice treated twice daily with NS or MEH158. After 72 h of infection, no severe pathological signs were detected in the lungs of Iinf mice treated twice daily with EB211, EB279, or CKT for 72 h. Black arrows: bacterial foci, Black arrowheads: necrosis of bronchial epithelial cells, Black asterisks: edema of perivascular spaces, Red arrow: macrophage accumulation in the perivascular and peribronchial areas, White arrows: infiltration of inflammatory cells (neutrophils and mononuclear cells) in the perivascular and peribronchial areas, and parenchymal necrosis, White asterisks: areas of hemorrhage within alveoli and interstitium