Modified poly(L-lysine)-based structures as novel antimicrobials for diabetic foot infections, an in-vitro study

Background: Wound infections occur as sequelae to skin trauma and cause significant hospitalizations, morbidity and mortality. Skin traumas arise more frequently in those with diabetes or cardiovascular disease and in these settings, may be chronic with poorer outcomes including lower limb amputation. Treatment of chronic wound infection is challenging due to antibiotic resistance and biofilm formation by bacteria including S. aureus and P. aeruginosa, which are among the most frequent causative pathogens. Managing these challenging infections requires new molecules and modalities. Methods: We evaluated antimicrobial and anti-biofilm activity of star-shaped poly(L-lysine) (PLL) polymers against S. aureus and P. aeruginosa strains and clinical isolates recovered from wounds including diabetic foot wounds (DFW) in a Dublin Hospital in 2019. A star-shaped PLL polypeptide series, specifically G2(8)PLL20, G3(16)PLL10, G4(32)PLL5 with variation in polypeptide chain length and arm-multiplicity, were compared to a linear peptide, PLL160 with equivalent number of lysine residues. Results: All PLLs, including the linear polypeptide, were bactericidal at 1mM against S. aureus 25923 and P. aeruginosa PAO1, with log reduction in colony forming units/ml between 2.7-3.6. PLL160 demonstrated similar killing potency against 20 S. aureus and five P. aeruginosa clinical isolates from DFW, mean log reductions: 3.04 ± 0.16 and 3.96 ± 0.82 respectively after 1 hour incubation. Potent anti-biofilm activity was demonstrated against S. aureus 25923 but for clinical isolates, low to moderate loss of biofilm viability was shown using PLL160 and G3(16)PLL10 at 50 mM (S. aureus) and 200 mM (P. aeruginosa) with high inter-isolate variability. In the star-shaped architecture, antimicrobial activity was retained with incorporation of 5-mer hydrophobic amino-acid modifications to the arms of the polypeptides (series G3(16)PLL20-coPLT5, G3(16)PLL20-coPLI5, G3(16)PLL20-coPLP5). Conclusion: These polypeptides offer structural flexibility for clinical applications and have potential for further development, particularly in the setting of diabetic foot and other chronic wound infections.

Diabetic wound healing approaches: an update

Diabetic wounds are of profound clinical importance. Despite immense efforts directed towards its management, it results in the development of amputations, following a diagnosis of diabetic foot. With a better understanding of the complexities of the microbalance involved in the healing process, researchers have developed advanced methods for the management of wounds as well as diagnostic tools (especially, for wound infections) to be delivered to clinics sooner. In this review, we address the newer developments that hope to drive the transition from bench to bedside in the coming decade.

A Study of Early Parenteral Nutritional Support and Factors Associated with Clinical Outcomes in Major Pediatric Burn Patients

Objectives: Adequate nutritional support is one of the challenging treatments of major pediatric burns. Parenteral nutrition (PN) is one of the options to achieve daily caloric goal. Latest nutritional guidelines recommend late PN initiation due to unclear benefit over risk based on the limited data. Our study provides the data of parenteral nutrition within 7 days post admission (early PN) and factors affecting clinical outcomes in major pediatric burn patients. Methods: A retrospective study was conducted regarding pediatric burn patients who had over 15% of their total body surface area (TBSA) with second- or third-degree burns. All the patients were classified as requiring early PN support or non-early PN support. Results: 124 major pediatric burns were reviewed. Eighty-six patients (65.2%) were male, and the median age was three years (0.3-15 years). Early PN showed no association with length of hospital stay (LOS) (p=0.480) or a 30-day mortality (p=0.529). The children’s age, wound infections, and abdominal distension were the independent associated factors of LOS (p=0.025, 0.001, and 0.003 respectively). Pneumonia and urinary tract infection were independent factors associated with 30-day mortality (p=0.025). Conclusions: Early PN in acute pediatric burns was not associated with LOS or 30-day mortality. It can be considered as options of nutritional support in acute, major pediatric burns. Effective management of wound infections and abdominal distension may reduce LOS.

Novel Approach of Phyto-Mediated Thermo-Sensitive and Biocompatible Nano-Formulation to Improve Anti-Microbial Efficacy Against Pathogenic Bacterial for the Treatment of Wound Infections

Design and development of novel methods for the synthesis of metal nanopartilces (MNPs) was greatly attracted by research community due to various applications. We described a greener strategy for the synthesis of silver nanoformulation (Ag NF) using leaf extract of Ziziphus zizyphus and then surface functionalized using P(NIPAM-co-MQ). The synthesized AgNPs were characterized by UV-visible spectroscopy and Transmission electron microscopy. Further, the functionalized AgNPs were characterized XPS and x-ray diffraction studies. The design of bioactive and biocompatible Ag nanoformulation preparations have been provide promising alternative source for bacterial-related therapies. The developed Ag NF have demonstrated predominant bactericidal action with highinhibition rate and long-term efficiency against clinically approved bacterial pathogens (S. aureus and E. coli), which greatly contributed treatment of wound infections. The observations of the present study could provide new avenue for the antimicrobial treatment of wound therapy

Nitric Oxide-Releasing Bacterial Cellulose/Chitosan Crosslinked Hydrogels for the Treatment of Polymicrobial Wound Infections

Polymicrobial wound infections are a major cause of infectious disease-related morbidity and mortality worldwide. In this study, we prepared a nitric oxide (NO)-releasing oxidized bacterial cellulose/chitosan (BCTO/CHI) crosslinked hydrogel to effectively treat polymicrobial wound infections. Linear polyethyleneimine diazeniumdiolate (PEI/NO) was used as the NO donor. The aldehyde group of BCTO and the amine of CHI were used as crosslinked hydrogel-based materials; their high NO loading capacity and antibacterial activity on the treatment of polymicrobial-infected wounds were investigated. The blank and NO-loaded crosslinked hydrogels, namely BCTO-CHI and BCTO-CHI-PEI/NO, were characterized according to their morphologies, chemical properties, and drug loading. BCTO-CHI-PEI/NO exhibited sustained drug release over four days. The high NO loading of BCTO-CHI-PEI/NO enhanced the bactericidal efficacy against multiple bacteria compared with BCTO-CHI. Furthermore, compared with blank hydrogels, BCTO-CHI-PEI/NO has a favorable rheological property due to the addition of a polymer-based NO donor. Moreover, BCTO-CHI-PEI/NO significantly accelerated wound healing and re-epithelialization in a mouse model of polymicrobial-infected wounds. We also found that both crosslinked hydrogels were nontoxic to healthy mammalian fibroblast cells. Therefore, our data suggest that the BCTO-CHI-PEI/NO developed in this study improves the efficacy of NO in the treatment of polymicrobial wound infections.