Background Diabetic foot ulcers (DFUs) are a significant worldwide health burden, worsened by biofilms that encourage chronicity and resistance to antibiotics. To improve the outcomes of diabetic infections, it is important to know how biofilms work, how they interact with each other, how they spread, and what problems they cause in therapy. Methods A narrative literature search was conducted in PubMed, Scopus, Google Scholar, and Web of Science to investigate biofilm formation pathways (e.g., the icaADBC operon in Staphylococcus aureus and quorum sensing genes such as las / rhl , and pelA in Pseudomonas aeruginosa ), polymicrobial interactions, global prevalence, and associated therapeutic challenges. We reviewed recent primary studies and influential review articles (2020–2026). Results Biofilms, predominantly polymicrobial (60–80% of DFUs), often comprise Staphylococcus aureus (34.34% in sub-Saharan Africa, over 30% in Western countries), P. aeruginosa (11.1–18.5%), and Escherichia coli (21.16%). Hyperglycemia and advanced glycation end products enhance biofilm formation via σB overexpression and metabolic cooperation, hence promoting virulence and the progression of Wagner grade. Extracellular polymeric substance (EPS), and efflux pumps impede the efficacy of antibiotics such as vancomycin and linezolid. Surgical interventions (such as debridement and osteotomies) and novel therapies (including nisin, silver sulfadiazine, and rhamnolipid-coated nanoparticles) possess potential in combating resistance and promoting recovery. Conclusion In conclusion, biofilm development significantly contributes to the chronicity and treatment resistance of DFUs, shaped by complex host-pathogen and polymicrobial interactions. Combining novel antibiofilm medicines with traditional wound care in a multimodal strategy offers promise for improved healing outcomes, but further clinical trials are needed to be certain. Clinical trial number Not applicable.
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Karimbakhsh et al. (2026) studied this question.
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