الفهرس 
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Abstract
Diabetic foot ulcer (DFU) represented the most feared diabetic complication that caused the hospitalization of the diabetic patient. DFU usually characterized with delayed healing as, the diabetic neuropathy, angiopathy, and ulcer concomitant infections, among them are multi-drug resistant (MDR) bacteria that emphasized the clinical importance for developing new therapeutic strategy with safe and effective alternatives for the antibiotics to overcome DFU-MDR bacterial infection. Bacteriophage therapy considered a novel approach to eradicate the MDR but it is role in the ploy microbial infection of the DFU remains elusive. Thus, the current work was designed to investigate the effect of the topical application of the phage cocktail on the healing of the diabetic wound infected with clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella variicola, Escherichia coli and Proteus mirabilis. Bacterial isolation was performed form clinical hospitalized and non-hospitalized cases of DFU, identified morphologically, biochemically, molecularly via 16S rRNA sequencing, and typed for the antibiotic resistance pattern. Moreover, phages were isolated from sewage water and identified with electron microscope. Forty-five adult male Sprague-Dawely rats were assigned in 3 groups (15 rats each), namely, the diabetic infected wound group, diabetic infected wound ceftriaxone treated group, and the diabetic infected wound phage cocktail treated group. The results revealed that phage cocktail had a superior effect over the ceftriaxone in wound healing parameters; wound size, wound index, wound bacterial load, mRNA expression of; wound healing markers (Collagen 1a, Fibronectin 1, Matrix Metalloproteinases (MMP9), Proliferating cell nuclear antigen (PCNA) and Transforming growth factor beta (TGF-β), inflammatory markers; Tumor Necrosis Factor alpha (TNF-α), Nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κβ), Interleukin 1 β (IL-1β), Interleukin -8 (IL-8), and Monocyte chemotactic protein 1 (MCP-1), anti-inflammatory markers (Interleukin10 (IL-10) & Interleukin4 (IL4), and diabetic wound collagen deposition, also, the histomorphic picture of the diabetic infected wound. Based on the current findings it could be speculated that, phage therapy could be considered a novel antibiotic substitute in the DFU with MDR-poly microbial infection therapeutic strategies.
Keywords
Diabetic foot ulcer, Polymicrobial infection, Multi-drug resistant bacteria, Bacteriophage therapy, bacteriophages cocktail and wound healing.