A68-01 Bacteriophage Cocktail Therapy Enhances Survival and Suppresses Inflammation During Pseudomonas Aeruginosa Pneumonia

作者：H. Lu, D. Van Tyne, Y. Di · 发表于：American Journal of Respiratory and Critical Care Medicine · 年份：2026 · DOI：10.1093/ajrccm/aamag162.4157

The emergence of antimicrobial resistance in Pseudomonas aeruginosa has made the treatment of pneumonia increasingly difficult. Bacteriophages offer a narrow-spectrum, self-replicating alternative to antibiotics. We evaluated the therapeutic and tissue-protective effects of a three-phage cocktail against acute P. aeruginosa infection in mice.C57BL/6 mice were infected intratracheally with 1 × 108 CFU of P. aeruginosa PAO1. Two hours later, animals received 50 µL of a phage cocktail containing PSA7, PSA16, and PSA39 (1.5 x 107 PFU/mouse, MOI ≈ 0.15) via intratracheal instillation. Five-fold (3 x 106 PFU/mouse, MOI ≈ 0.03) and ten-fold (1.5 x 106 PFU/mouse, MOI ≈ 0.015) dilutions of the original phage cocktail were further tested to assess dose response. Survival, bacterial load in bronchoalveolar lavage (BAL) and lung tissue, cytokine mRNA levels, immune-cell profiles, and lung histology were examined at day 2 and day 5 post-infection.All phage-treated mice survived and recovered quickly through day 5 of the experiment, whereas most PBS-treated controls without phage cocktail died within 36 hours (p < 0.0001). Phage therapy reduced bacterial counts by 3-4 log10 CFU and lowered the expression of IL-1β, IL-6, TNF-α, CXCL10, and CCL12 to baseline levels. Flow cytometry showed decreased neutrophil activation and altered macrophage and T-cell composition.Histological analysis revealed severe alveolar consolidation, hemorrhage, and dense peribronchial infiltration in PBS-treated lun...