Absence of Synergism between a Dual-AMP Biogel and Antibiotics Used as Therapeutic Agents for Diabetic Foot Infections.

Diabetic foot infections (DFIs) are frequently linked to diabetic-related morbidity and death because of the ineffectiveness of conventional antibiotics against multidrug-resistant bacteria. Pexiganan and nisin A are antimicrobial peptides (AMPs), and their application may complement conventional antibiotics in DFI treatment. A collagen 3D model, previously established to mimic a soft-tissue collagen matrix, was used to evaluate the antibacterial efficacy of a guar gum gel containing pexiganan and nisin alone and combined with three antimicrobials toward the biofilms of Staphylococcus aureus and Pseudomonas aeruginosa isolated from infected foot ulcers. Antimicrobials and bacterial diffusion were confirmed by spot-on-lawn and bacterial growth by bacterial count (cfu/mL). Our main conclusion was that the dual-AMP biogel combined with gentamicin, clindamycin, or vancomycin was not able to significantly reduce bacterial growth or eradicate S. aureus and P. aeruginosa DFI isolates. We further reported an antagonism between dual-AMP and dual-AMP combined with antibiotics against S. aureus.

Influence of Storage on the Antimicrobial and Cytotoxic Activities of a Nisin-biogel with Potential to be Applied to Diabetic Foot Infections Treatment.

Staphylococcus aureus is the most prevalent pathogen in diabetic foot infections (DFIs). In addition to its ability to express several virulence factors, including the formation of recalcitrant biofilms, S. aureus is also becoming increasingly resistant to most antibiotics used in clinical practice. The search for alternative treatment strategies for DFI is urgently needed. Antimicrobial peptides (AMPs), namely, nisin, are emerging as potential new therapeutics for managing DFIs. Our team has developed a nisin-guar gum biogel to be applied to DFIs. In this study, to confirm its future in vivo applicability, we evaluated the influence of four storage temperatures (-20 °C, 4 °C, 22 °C, and 37 °C) during a 24 months storage period on its antimicrobial activity towards DFI S. aureus, and its cytotoxicity, to a human keratinocyte cell line. When stored at temperatures below 22 °C, the biogel antimicrobial activity was not significantly influenced by storage duration or temperature. Moreover, nisin incorporated within the guar gum biogel exhibited no significant levels of cytotoxicity on human keratinocyte cells, confirming its potential for DFIs therapeutics. In conclusion, results confirm that the nisin-biogel is a potential candidate to be used as an alternative or complement compound for conventional DFI therapeutics.