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DFU was usually characterized with delayed healing as the diabetic neuropathy, angiopathy, and ulcer concomitant infections, among them, are multidrug-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 was considered a novel approach to eradicate the MDR, but its role in the polymicrobial 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\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    ,\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    ,\n                    <jats:italic>Klebsiella variicola<\/jats:italic>\n                    ,\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    , and\n                    <jats:italic>Proteus mirabilis<\/jats:italic>\n                    . Bacterial isolation was performed from clinical hospitalized and non-hospitalized cases of DFU, identified morphologically, biochemically, molecularly via\n                    <jats:italic>16\u00a0s rRNA<\/jats:italic>\n                    sequencing, and typed for the antibiotic resistance pattern. Moreover, phages were isolated from the aforementioned clinical isolates and identified with electron microscope. Forty-five adult male Sprague\u2013Dawley 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, and mRNA expression); wound healing markers (\n                    <jats:italic>Cola1a<\/jats:italic>\n                    ,\n                    <jats:italic>Fn1<\/jats:italic>\n                    ,\n                    <jats:italic>MMP9<\/jats:italic>\n                    ,\n                    <jats:italic>PCNA<\/jats:italic>\n                    , and\n                    <jats:italic>TGF-\u03b2<\/jats:italic>\n                    ); inflammatory markers (\n                    <jats:italic>TNF-\u03b1<\/jats:italic>\n                    ,\n                    <jats:italic>NF-\u03ba\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>IL-1\u03b2<\/jats:italic>\n                    ,\n                    <jats:italic>IL-8<\/jats:italic>\n                    , and\n                    <jats:italic>MCP-1<\/jats:italic>\n                    ); anti-inflammatory markers (\n                    <jats:italic>IL-10<\/jats:italic>\n                    and\n                    <jats:italic>IL-4<\/jats:italic>\n                    ); and diabetic wound collagen deposition; and 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-polymicrobial infection therapeutic strategies.\n                  <\/jats:p>","DOI":"10.1007\/s10123-022-00293-2","type":"journal-article","created":{"date-parts":[[2022,11,9]],"date-time":"2022-11-09T09:02:49Z","timestamp":1667984569000},"page":"343-359","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":44,"title":["Bacteriophage therapy as an alternative technique for treatment of multidrug-resistant bacteria causing diabetic foot infection"],"prefix":"10.1007","volume":"26","author":[{"given":"Amira Mohamed","family":"Ghanaim","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammed Abdulaziz","family":"Foaad","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eman Zakaria","family":"Gomaa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Khalid Abdelfatah El","family":"Dougdoug","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gamal Eldidamony","family":"Mohamed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Hamed","family":"Arisha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tarek","family":"Khamis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,9]]},"reference":[{"issue":"6","key":"293_CR1","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1517\/14656566.2015.1021780","volume":"16","author":"M Abbas","year":"2015","unstructured":"Abbas M, Uc KI, Lipsky BA (2015) In diabetic foot infections antibiotics are to treat infection, not to heal wounds. 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