# Development and Control of Biofilms in Diabetic Foot Infections: A Narrative Review
## 13 Conventional Treatment  
The conventional treatment for methicillin-resistant _Staphylococcus aureus_ (MRSA) is vancomycin. However, due to the widespread resistance observed in _S. aureus_[122; 123; 124], linezold is often prescribed for MRSA infections. Linezold is an oxazolidinone effective against both methicillin-resistant and vancomycin-resistant _S. aureus_, as well as against streptococci and enterococci. Other treatment options include combinations of piperacillin and taxobactam, ticacillin and clavulanic acid, or ampicillin and sulbactam, which are broad-spectrum antibiotics used for moderate to severe infections. Carbapenem antibiotics are commonly used for treating multidrug-resistant Gram-negative organisms. However, due to extensive resistance to these drugs, treatment guidelines now recommend clin  
Figure 5: Approaches for treatment of biofilm mediated diabetic foot ulcers.  
damycin combined with piperacillin-tazobactam or cefoperazone-sublactam [125]. Other options include cefepime with amikacin, imipenem, gentamicin, and taxobactam [126].  
Debridement is another effective method for removing bacterial biofilms [127]. Active debridement involves removing necrotic tissue around the wound using either a scalpel or hydro-surgical debridement with a jet spray of water [128]. Topical antimicrobial solutions, such as 10% povidence-iodine, are effective in eradicating bacterial biofilms [129]. Cadexomer iodine, encapsulated in small polysaccharide beads, can also effectively reduce biofilm formation [130; 131].  
Enzymes like \(\alpha\)-amylase and collagenase are effective in degrading extracellular polysaccharides and collagen incorporated into biofilms. For instance, \(\alpha\)-amylase reduced Staphylococcus aureus biofilm density, while collagenase treatment negated the protective effects of biofilm-incorporated collagen, facilitating immune cell phagocytosis. Quorum-sensing inhibitors, such as acylase, were shown to disrupt bacterial communication critical for biofilm formation [66; 73]. Combined with matrix-degrading enzymes like \(\alpha\)-amylase, these approaches significantly reduced biofilm biomass [132]. Advanced hydrogel systems loaded with biofilm-targeting nanoparticles or antimicrobial peptides, such as the TP-Mg@PSG hydrogel and nisin-loaded guar gum, demonstrate localized delivery and effective biofilm disruption while promoting wound healing have been developed, while by ultrasonic waves have been shown to mediate activation of graphitic carbon nitride sheets causing sonocatalytic hydrogen mediated biofilm lysis [133]. Phage therapy and bacteriophage-derived enzymes like endolysins show promise in dismantling biofilms by lysing bacterial cell walls within biofilm matrices [45; 46]. Antimicrobial photodynamic therapy (A-PDT) utilizing indocyanine green and EDTA demonstrated synergistic effects with antibiotics to disrupt biofilms in vitro [134].  
Studies employing microfluidic systems mimicking the diabetic wound environment confirmed the efficacy of daptomycin and ceftazidime in combination therapy for biofilm eradication [1]. Controlled nitric oxide (NO)-releasing nanoparticles effectively dispersed MRSA biofilms in diabetic wound models, enhancing healing outcomes.