Many diabetic foot ulcers (DFUs) stall despite adequate offloading, glycemic control and perfusion. One explanation that has gained substantial attention over the past decade is the presence of microbial biofilm in the wound bed. Understanding what biofilm is, how common it is, and why it complicates treatment helps explain why some ulcers become chronic and why repeated, structured wound care is emphasized in current practice.
What Is a Biofilm?
A biofilm is a community of microorganisms embedded in a self-produced matrix of extracellular polymeric substances that adheres to a surface, including wound tissue. In a review published in Microorganisms, Pouget and colleagues (2020) describe biofilms as a main contributor to delayed healing and wound chronicity in DFUs. Organisms within a biofilm behave differently from free-floating (planktonic) bacteria: they are shielded from host immune cells and tolerate antimicrobial agents far more readily.
Because the foot in diabetes often combines neuropathy, ischemia and impaired immune function, it provides a favourable environment for persistent, polymicrobial communities. The review notes that polymicrobial biofilms tend to be thicker and harder to eradicate, and that fungal communities have been associated with poorer prognosis and delayed healing.
How Common Is Biofilm in Chronic Wounds?
Malone and colleagues (2017), in a systematic review and meta-analysis in the Journal of Wound Care, pooled nine studies covering 185 chronic wounds and estimated that 78.2% (95% CI 61.6–89) contained biofilm. This is consistent with the often-cited range of 60–80% for chronic wounds, compared with a much lower proportion in acute wounds in earlier work. Specific to diabetic foot infection, studies summarized by Pouget et al. found biofilm in roughly two-thirds of cases in one cohort of 162 infections.
These figures carry caveats. The meta-analysis included a relatively small number of wounds, and the authors of the 2020 review point out that much biofilm research relies on laboratory or animal models that may not fully reflect clinical conditions. Biofilm is also rarely visible to the naked eye, so prevalence estimates depend heavily on the detection method used.
Why Biofilm Complicates Treatment
Antibiotic tolerance
Laboratory data summarized by Pouget et al. show that biofilm-embedded Staphylococcus isolates from DFUs can be 10 to 1,000 times more tolerant to antibiotics than their planktonic counterparts, and that most agents tested in one study failed to eradicate established biofilm. Low-oxygen conditions, common in ischemic wounds, can further reduce the activity of some antibiotics. For this reason, systemic antibiotics alone are generally not expected to clear biofilm from a wound bed.
Diagnostic limitations
Distinguishing colonization from true infection remains one of the central challenges. Pouget et al. report that tissue biopsy is the most reliable sample type, whereas swabs of the wound surface are prone to contamination with skin flora. Specialized methods such as confocal or scanning electron microscopy and fluorescence in situ hybridization can visualize biofilm directly but are largely research tools. The 2023 IWGDF/IDSA guideline on diabetes-related foot infection (Senneville et al., Diabetes/Metabolism Research and Reviews, 2024) addresses how infection and its severity are classified, how microbiological samples should be collected and processed, and when surgical treatment is appropriate, reflecting that clinical assessment guides therapy rather than culture results alone.
Debridement and Biofilm-Based Wound Care
Mechanical debridement is regarded as the essential first step in managing suspected biofilm. Pouget et al. state that it is the preferred approach but may not remove all biofilm, and that it typically needs to be repeated at regular intervals because biofilm can reform quickly. A Global Wound Biofilm Expert Panel (Schultz et al., Wound Repair and Regeneration, 2017) used a modified Delphi process to reach consensus on 61 statements covering biofilm identification and treatment, including mechanical debridement and topical antiseptics. From these, the panel proposed a stepped-down approach: initial aggressive removal of devitalized tissue and biofilm, followed by measures intended to discourage reattachment while the wound heals.
Other strategies under investigation include chelating agents, quorum-sensing modulators, dispersal agents, antimicrobial peptides, bacteriophage therapy and honey-based products. Most of this evidence is preclinical or early clinical, and none replaces standard care.
Key Takeaways
Biofilm is present in a large majority of chronic wounds, including many DFUs, and is a plausible contributor to stalled healing. It tolerates antibiotics and evades the immune system, which limits what systemic therapy alone can achieve. Surface swabs are unreliable, and direct biofilm visualization is not yet practical in routine care. Repeated debridement, alongside offloading, perfusion assessment and infection management, remains the foundation of treatment, while higher-quality clinical trials are still needed for anti-biofilm adjuncts.
References
- Malone M, Bjarnsholt T, McBain AJ, et al. The prevalence of biofilms in chronic wounds: a systematic review and meta-analysis of published data. J Wound Care. 2017.
- Pouget C, Dunyach-Remy C, Pantel A, Schuldiner S, Sotto A, Lavigne J-P. Biofilms in diabetic foot ulcers: significance and clinical relevance. Microorganisms. 2020;8(10):1580.
- Schultz G, Bjarnsholt T, James GA, et al. Consensus guidelines for the identification and treatment of biofilms in chronic nonhealing wounds. Wound Repair Regen. 2017;25(5):744–757.
- Senneville É, Albalawi Z, van Asten SA, et al. IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections (IWGDF/IDSA 2023). Diabetes Metab Res Rev. 2024;40(3):e3687.
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