# Development and Control of Biofilms in Diabetic Foot Infections: A Narrative Review
## 16 Strategies Used for Treatment of Biofilm in DFI  
The approaches that are currently being used or studied for treatment of biofilms formed by pathogens in diabetic foot infections or diabetic foot ulcer wounds vary greatly in the types of strategies that they utilize to eliminate the recalcitrant biofilms. The treatment strategies range from entities of chemical and biological origin, like antibiotics, synthetic peptides, biological molecules like enzymes, to natural extracts derived from plants. A sum marized list of the strategies used by conventional and alternative treatment methods that are currently available or in development are listed in Table 4. In addition to pharmaceutical and chemical agents, novel biologically sourced and biosimilar peptide-based anti-biofilm agents are also listed in Table 4 along with a brief description of their therapeutic strategies and relevant usage information. \begin{table}
\begin{tabular}{c c c} \hline \begin{table}
\begin{tabular}{c c c} \hline
**Treatment** & **Description** & **References** \\ \hline Tobramycin powder bolus & Large initial antibiotic concentration & [172] \\ \hline Calcium sulphate beads with PMMA & Greater area under the concentration-time curve (AUC) compared to antibiotics loaded PMMA & \\ loaded space & space alone & [172; 173] \\ (Tobramycin) & Largest concentration of antibiotics & \\  & Potentially cytotoxic & \\ \hline  & Cytotoxic and interferes with proliferation and & \\  & osteogenic differentiation of human bone & \\  & marrow-derived mesenchymal stem cells with & \\  & increasing degree of substitution of the & \\  & quaternary ammonium. & \\  & the quaternary ammonium) HACC- & Potential obstacle: & [173; 174] \\  & loaded PMMA & \\  & \(\bullet\) & Larger particle size of 26\% HACC particles \\  & & leading to slower release from PMMA \\  & \(\bullet\) & Slow elution of antibiotics \\ \hline  & \(\bullet\) & Decreases number of viable MRSA (methicillin \\  & & resistant _S. aureus_) & \\ Gentamicin-loaded PMMA & \(\bullet\) & Rapid initial release & [173; 174] \\  & \(\bullet\) & Less effective at biofilm inhibition & \\ \hline  & \(\bullet\) & Disturbs the cell membrane integrity therefore & \\  & & dysregulating their communication & \\  & \(\bullet\) & Inhibits and eradicates mono and dual & [175] \\  & & species biofilm & \\  & & Inhib biofilm grown under shear stress destructing & \\  & its structure & \\ \hline Silver nanoparticle functionalized & \(\bullet\) & Inhibits formation of cross kingdom, bacterial & \\  & silicone elastomer & and fungal, biofilm in a dose dependent & [176] \\ \hline Cold atmospheric plasma & Break peptidoglycan bond of gram-positive bacteria & [177] \\  & in biofilm & \\ \hline  & \(\bullet\) & Phage lysins cleave the peptidoglycan layer of & \\  & the cell wall. & [178] \\  & & Eradicate preformed biofilm & \\ \hline Mannosidase and glucanasa & Hydrolyses mannan-glucan in C.Auris biofilm & [178] \\ \hline  & Alginate lyase & Removes exopolysaccharideacharide from the surface & [178] \\  & promoting biofilm eradication & \\ \hline Magnetic iron oxide nanoparticles with & Causes mechanical damage to the matrix of the & \\  & magnet fields & biofilm leading to eradication. & [178] \\ \hline Magneto-responsive gallium-based liquid & Disrupts matrix, results in bacterial lysis & [178] \\  & metal droplet & \\ \hline  & \(\bullet\) & Degrades the extracellular DNA in biofilms. \\ DNase & Inhibits formation and eradicates already & [178] \\  & formed biofilm & \\ \hline \end{tabular}
\end{table} 
Table 4: _Cont._The inhibition and eradication of biofilm in foot ulcers is effective with combination therapy rather than a single drug therapy to properly and effectively treat the chronicity of diabetic foot ulcers caused by bacterial/fungal/mixed biofilm formation [181]. However, there are concerns surrounding the use of some of the agents.