<![CDATA[Diabetes mellitus (DM) enhances the risk of diabetic foot infections (DFIs) due to hyperglycemia-induced immune dysfunction and compromised wound healing. This review explores the mechanisms connecting immune dysfunction to DFIs, outlines the primary causative pathogens, assesses laboratory diagnostic methods, and proposes strategies to enhance DFI management, especially in resource-constrained environments. A systematic literature review was performed using PubMed, Scopus, ScienceDirect, and Google Scholar, with additional backward reference list searching. Publications from 2012 to 2024 were included. Out of 60 identified records, 24 duplicates were excluded, and 36 records were screened. Ultimately, 20 eligible publications were incorporated into the qualitative thematic synthesis. The evidence suggests that chronic hyperglycemia impairs neutrophil chemotaxis, phagocytosis, and cytokine responses, while promoting NETosis, oxidative stress, and mitochondrial dysfunction, thus contributing to the onset and persistence of DFIs. These infections are often polymicrobial, frequently involving Staphylococcus aureus, including methicillin-resistant strains, Pseudomonas aeruginosa, Escherichia coli, and other multidrug-resistant organisms. Conventional culture and antimicrobial susceptibility testing remain essential, although molecular methods and inflammatory biomarkers can supplement diagnosis but encounter resource-related implementation challenges. Enhancing laboratory capacity, local microbiological surveillance, timely targeted therapy, and multidisciplinary care may improve DFI management and mitigate severe outcomes, such as treatment failure and amputation.]]>
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