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BACKGROUND: Carbapenem-resistant Pseudomonas aeruginosa commonly leads to difficult-to-treat infections necessitating new therapeutics. Recently, bacteriophages have gained attention as promising alternatives. This study aimed to isolate, characterize virulent phages from various water sources against clinical carbapenem-resistant P. aeruginosa isolates to formulate a phage cocktail, and evaluate its in vivo efficacy using a mouse burn wound infection model. RESULTS: Biological and genomic characterization of isolated phages were determined by host range, temperature and pH stability, transmission electron microscopy analysis, and whole-genome sequencing. Three virulent phages without carrying antibiotic resistance, virulence or lysogeny-related gene included in the study and named as BaskentP1₁12 (Φ1), BaskentP2ICU (Φ2) and BaskentP3₃B (Φ3). Φ1 exhibited podovirus-like morphology, while Φ2 and Φ3 displayed myovirus-like morphology. MOI values were determined as 100, 1, and 10, with corresponding burst sizes of 123, 288 and 115 PFU/CFU, respectively. All three phages were stable at temperatures between 4 and 50 °C; and pH 4-10, Φ1 and Φ3 were completely inactive at pH 2 and 12. Phages with diverse receptor binding site proteins exhibited complementary lytic activity profiles across different and overlapping sets of carbapenem-resistant P. aeruginosa isolates were used for formulation the phage cocktail thereby achieving a broad host range. The therapeutic efficacy of the phage cocktail was compared with antibiotic treatment in 45 Balb/c mice, divided into five groups. Blood and tissue samples were collected for CRP analysis, bacterial load, and histopathological examination. Wound surfaces were measured daily, and survival percentages were recorded. CONCLUSION: Compared to the untreated control group, phage therapy significantly reduced CRP levels and bacterial loads, enhanced wound healing, and improved survival rates without any toxicity. These results demonstrate that the formulated phage cocktail is a promising alternative treatment with a protocol adaptable for on-demand clinical use.
Vural et al. (Thu,) studied this question.