A novel antimicrobial peptide Scyreptin1-30 from Scylla paramamosain exhibiting potential therapy of Pseudomonas aeruginosa early infection in a mouse burn wound model.

Antimicrobial resistance (AMR) constitutes a significant global threat to human health. In recent years, there has been a concerning surge in infections caused by multidrug-resistant bacteria, highlighting the pressing need to urgently explore novel and effective alternatives to conventional antibiotics. Antimicrobial peptides (AMPs) have emerged as a focal point of research, capturing significant attention as promising antimicrobial agents. In this study, we have identified a novel cationic antimicrobial peptide (AMP) named Scyreptin1-30, derived from the marine invertebrate Scylla paramamosain. The results showed that Scyreptin1-30 exhibits a broad-spectrum antimicrobial activity, demonstrating significant potency against both bacteria and fungi, and even against the clinically isolated multidrug-resistant bacteria Pseudomonas aeruginosa. Moreover, Scyreptin1-30 exhibited rapid bactericidal kinetic. The results of antibacterial mechanism showed that Scyreptin1-30 destroyed the integrity of bacterial membranes, leading to bacterial death and exhibited potent anti-biofilm activity against P. aeruginosa. The activity of Scyreptin1-30 against bacteria had a favorable thermal stability, displayed a certain ion tolerance, and showed no discernible cytotoxicity when assessed against both the mammalian cell line HEK293T and the fish cell lines ZF4. In an In vivo study, Scyreptin1-30 exhibited a remarkably reduction in the bacterial load caused by multidrug-resistant P. aeruginosa at the site of infection, and promoted wound healing in a mouse model of burn infection. This study indicated that Scyreptin1-30 holds promise as an effective antibacterial agent, potentially serving as a topical skin treatment against multidrug-resistant bacterial infections, including those caused by P. aeruginosa.

REMOTE BURN INJURY IN AGED MICE INDUCES COLONIC LYMPHOID AGGREGATE EXPANSION AND DYSBIOSIS OF THE FECAL MICROBIOME WHICH CORRELATES WITH NEUROINFLAMMATION.

ABSTRACT: The Earth's population is aging, and by 2050, one of six people will be 65 years or older. Therefore, proper treatment of injuries that disproportionately impact people of advanced age will be more important. Clinical studies reveal people 65 years or older account for 16.5% of all burn injuries and experience higher morbidity, including neurocognitive decline, and mortality that we and others believe are mediated, in part, by heightened intestinal permeability. Herein, we used our clinically relevant model of scald burn injury in young and aged mice to determine whether age and burn injury cooperate to induce heightened colonic damage, alterations to the fecal microbiome, and whether resultant changes in the microbiome correlate with neuroinflammation. We found that aged, burn-injured mice have an increase in colonic lymphoid aggregates, inflammation, and proinflammatory chemokine expression when compared with young groups and sham-injured aged mice. We then performed fecal microbiota sequencing and found a striking reduction in gut protective bacterial taxa, including Akkermansia , in the aged burn group compared with all other groups. This reduction correlated with an increase in serum fluorescein isothiocyanate-Dextran administered by gavage, indicating heightened intestinal permeability. Furthermore, loss of Akkermansia was highly correlated with increased messenger RNA expression of neuroinflammatory markers in the brain, including chemokine ligand 2, TNF-α, CXC motif ligand 1, and S100 calcium-binding protein A8. Finally, we discovered that postburn alterations in the microbiome correlated with measures of strength in all treatment groups, and those that performed better on the rotarod and hanging wire tests had higher abundance of Akkermansia than those that performed worse. Taken together, these findings indicate that loss of protective bacteria after burn injury in aged mice contributes to alterations in the colon, gut leakiness, neuroinflammation, and strength. Therefore, supplementation of protective bacteria, such as Akkermansia , after burn injury in aged patients may have therapeutic benefit.

Levofloxacin loaded clove oil nanoscale emulgel promotes wound healing in Pseudomonas aeruginosa biofilm infected burn wound in mice.

Owing to their tolerance to antibiotics, bacterial biofilms continue to pose a threat to mankind and are leading cause for non-healing of burn wounds. Within the biofilm matrix, antibiotics become functionally inactive due to restricted penetration and enzymatic degradation leading to rise of antimicrobial resistance. The objective of present investigation was to develop and characterize levofloxacin (LFX) loaded clove oil nanoscale emulgel (LFX-NE gel) and evaluate its in vivo therapeutic efficacy in Pseudomonas aeruginosa biofilm infected burn wound in mice. The optimized emulgel was found to possess good texture profile and showed shear thinning behavior. In vitro release study demonstrated complete drug release in 8 h and emulgel was found to be stable for 3 months at 25 °C and 40 °C. In vivo study revealed biofilm dispersal, complete wound closure, re-epithelialization and collagen deposition by LFX-NE gel in comparison to various control groups. LFX-NE gel was able to clear the infection within 7 days of treatment and promote wound healing as well. Therefore, administration of LFX-incorporated NE gel could be a beneficial treatment strategy for P. aeruginosa biofilm-infected burn wounds.

Phototherapy of Pseudomonas aeruginosa-Infected Wounds: Preclinical Evaluation of Antimicrobial Blue Light (450-460 nm) Using In Vitro Assays and a Human Wound Skin Model.

Objective: To determine effective treatment strategies against bacterial infections of burn wounds with Pseudomonas aeruginosa, we tested different treatment regimens with antibacterial blue light (BL). Background: Infections of burn wounds are serious complications and require effective and pathogen-specific therapy. Hereby, infections caused by P. aeruginosa pose a particular challenge in clinical practice due to its resistance to many antibiotics and topical antiseptics. Methods: LED-based light sources (450-460 nm) with different intensities and treatment times were used. Antibacterial effects against P. aeruginosa were determined by colony-forming unit (CFU) assays, human skin wound models, and fluorescence imaging. Results: In suspension assays, BL (2 h, 40 mW/cm2, 288 J/cm2) reduced bacterial number (>5 log10 CFU/mL). Applying 144 J/cm2, using 40 mW/cm2 for 1 h was more effective (>4 log10 CFU) than using 20 mW/cm2 for 2 h (>1.5 log10 CFU). BL with low irradiance (24 h, 3.5 mW/cm2, 300 J/cm2) only revealed bacterial reduction in thin bacteria-containing medium layers. In infected in vitro skin wounds only BL irradiation (2 h, 40 mW/cm2, 288 J/cm2) exerted a significant antimicrobial efficacy (2.94 log10 CFU/mL). Conclusions: BL treatment may be an effective therapy for P. aeruginosa-infected wounds to avoid radical surgical debridement. However, a significant antibacterial efficacy can only be achieved with higher irradiances and longer treatment times (min. 40 mW/cm2; >1 h), which cannot be easily integrated into regular clinical treatment protocols, for example, during a dressing change. Further studies are necessary to establish BL therapy for infected burns among tissue compatibility and interactions with previous therapeutic agents.

Epidemiology and Early Bacteriology of Extremely Severe Burns from an LPG Tanker Explosion in Eastern China.

The incidence of liquefied petroleum gas (LPG)-related accidents in China has increased over the recent years. In addition, infection remains a big challenge in cases of severe burns. Therefore, the present study aimed to provide valuable information for a better control of infections in the event of such disasters. In this study, a total of 16 patients who suffered extremely severe burns after an LPG tanker explosion were included. Thereafter, bacteriological culture results were collected within a week. Of 16 patients, 13 (81.25%) were male and the average age of all patients was 60.63 years. In addition, the mean burned area was 83.03% TBSA. Additionally, a total of 553 organism cultures were conducted out of which 287 isolates (51.90%) showed positive results. Notably, 38.52% were Gram-negative bacteria, 7.59% were Gram-positive bacteria and 5.79% were fungi. Moreover, the most prevalent Gram-negative bacteria were Stenotrophomonas maltophilia (28.97%) followed by Acinetobacter baumannii (28.53%), and Klebsiella pneumoniae (14.02%). On the other hand, the three most predominant Gram-positive bacteria were Enterococcus faecalis (33.33%), Staphylococcus aureus (28.89%) and Staphylococcus sciuri (17.78%). Furthermore, the most common fungi included Candida (38.24%), Fusarium (20.59%) and Aspergillus fumigatus (14.71%). With regard to the bacterial resistance patterns, carbapenem-resistant organisms included Acinetobacter baumannii (97.80%), Pseudomonas aeruginosa (67.57%), and Klebsiella pneumoniae (75.56%). In addition, Staphylococcus sciuri, Staphylococcus epidermidis, and Staphylococcus haemolyticus were identified to be methicillin-resistant. This study revealed that there was a high incidence of infection in victims of severe burns as a result of mass burn accidents, accompanied by early fungal infection.

Natural rubber dressing loaded with silver sulfadiazine for the treatment of burn wounds infected with Candida spp.

Millions of people are burned worldwide every year and 265,000 of the cases are fatal. The development of burn treatment cannot consist only of the administration of a single drug. Due to the infection risk, antibiotics are used in conjunction with gels and damp bandages. In this work, an inexpensive curative based on silver sulfadiazine (SS) and natural rubber latex (NRL) was developed to treat burn wounds. It was produced by the casting method. The infrared spectrum presented no interaction between drug and biopolymer. At the same time, electronic micrographs showed that the SS crystals are inserted on the polymeric dressing surface. Mechanical properties after the drug incorporation were considered suitable for dermal application. About 32.4% of loaded SS was released in 192 h by the dressings that also inhibited the growth of Candida albicans and Candida parapsilosis at 75.0 and 37.5 µg·mL-1, respectively. The curative proved to be biocompatible when applied to fibroblast cells, in addition to enhancing cellular proliferation and, in the hemocompatibility test, no hemolytic effects were observed. The good results in mechanical, antifungal and biological assays, combined with the average bandage cost of $0.10, represent an exciting alternative for treating burn wounds.

Improving the Inhibitory Effect of Phages against Pseudomonas aeruginosa Isolated from a Burn Patient Using a Combination of Phages and Antibiotics.

Antibiotic resistance causes around 700,000 deaths a year worldwide. Without immediate action, we are fast approaching a post-antibiotic era in which common infections can result in death. Pseudomonas aeruginosa is the leading cause of nosocomial infection and is also one of the three bacterial pathogens in the WHO list of priority bacteria for developing new antibiotics against. A viable alternative to antibiotics is to use phages, which are bacterial viruses. Yet, the isolation of phages that efficiently kill their target bacteria has proven difficult. Using a combination of phages and antibiotics might increase treatment efficacy and prevent the development of resistance against phages and/or antibiotics, as evidenced by previous studies. Here, in vitro populations of a Pseudomonas aeruginosa strain isolated from a burn patient were treated with a single phage, a mixture of two phages (used simultaneously and sequentially), and the combination of phages and antibiotics (at sub-minimum inhibitory concentration (MIC) and MIC levels). In addition, we tested the stability of these phages at different temperatures, pH values, and in two burn ointments. Our results show that the two-phages-one-antibiotic combination had the highest killing efficiency against the P. aeruginosa strain. The phages tested showed low stability at high temperatures, acidic pH values, and in the two ointments. This work provides additional support for the potential of using combinations of phage-antibiotic cocktails at sub-MIC levels for the treatment of multidrug-resistant P. aeruginosa infections.

Nanophyto-gel against multi-drug resistant Pseudomonas aeruginosa burn wound infection.

Burn wound is usually associated by antibiotic-resistant Pseudomonas aeruginosa infection that worsens and complicates its management. An effective approach is to use natural antibiotics such as cinnamon oil as a powerful alternative. This study aims to investigate topical nanostructured lipid carrier (NLC) gel loaded cinnamon oil for Pseudomonas aeruginosa wound infection. A 24 full factorial design was performed to optimize the formulation with particle size 108.48 ± 6.35 nm, zeta potential -37.36 ± 4.01 mV, and EE% 95.39 ± 0.82%. FTIR analysis revealed no excipient interaction. Poloxamer 407 in a concentration 20% w/w NLC gel was prepared for topical application. Drug release exhibited an initial burst release in the first five hours, followed by a slow, sustained release of up to five days. NLC-cinnamon gel has a significant ability to control the drug release with the lowest minimum inhibitory concentration again P. aeruginosa compared to other formulations (p < .05). In vivo study also showed NLC-cinnamon gel effectively healed the infected burned wound after a six-day treatment course with better antibacterial efficacy in burned animal models. Histological examination ensured the tolerability of NLC-cinnamon gel. The results suggest that nanoparticle-based cinnamon oil gel is a promising natural product against antibiotic-resistant strains of P. aeruginosa in wound infection.

Human organoid biofilm model for assessing antibiofilm activity of novel agents.

Bacterial biofilms cause 65% of all human infections and are highly resistant to antibiotic therapy but lack specific treatments. To provide a human organoid model for studying host-microbe interplay and enabling screening for novel antibiofilm agents, a human epidermis organoid model with robust methicillin-resistant Staphylococcus aureus (MRSA) USA300 and Pseudomonas aeruginosa PAO1 biofilm was developed. Treatment of 1-day and 3-day MRSA and PAO1 biofilms with antibiofilm peptide DJK-5 significantly and substantially reduced the bacterial burden. This model enabled the screening of synthetic host defense peptides, revealing their superior antibiofilm activity against MRSA compared to the antibiotic mupirocin. The model was extended to evaluate thermally wounded skin infected with MRSA biofilms resulting in increased bacterial load, cytotoxicity, and pro-inflammatory cytokine levels that were all reduced upon treatment with DJK-5. Combination treatment of DJK-5 with an anti-inflammatory peptide, 1002, further reduced cytotoxicity and skin inflammation.

Evaluation of Combined Ciprofloxacin and azithromycin free and nano formulations to control biofilm producing Pseudomonas aeruginosa isolated from burn wounds.

BACKGROUND: Nanoparticles are becoming increasingly important against resistant superbugs including Pseudomonas aeruginosa infections. AIMS: Exploration of Azithromycin as an adjunctive therapy to Ciprofloxacin for treatment of P. aeruginosa infections. Also, preparation of Ciprofloxacin-Azithromycin nanoparticles on chitosan nanocarrier (Cipro-AZM-CS) and assessment of its antimicrobial effect in vitro and in vivo. METHODS: Detection of biofilm production and biofilm-specific antibiotic resistance ndvB and tssC1 genes was attempted. Minimal inhibitory concentration (MIC) and Minimum biofilm eradication concentration (MBEC) were done in vitro for assessment of P. aeruginosa planktonic and biofilm forms eradication, respectively. In In vivo study, Cipro-AZM-CS and free form were used to evaluate survival rate, wound contraction and bacterial load in mice after third degree burn. RESULTS: All isolates were positive for biofilm production and ndvB and tssC1 genes. Majority of isolates (37, 74%) were extensively drug resistant. In the planktonic state, MIC values of Cipro-AZM free and CS forms were significantly lower than free Cipro MIC (P = 0.015 and P < 0.001 respectively). Also, Cipro-AZM free and CS MBEC values were significantly lower than that of free Cipro (P < 0.010 and P < 0.001 respectively). Furthermore, The MIC and MBEC values of free Cipro-AZM decreased significantly when challenged with Cipro-AZM-CS (P = 0.009 and P < 0.001 respectively). In vivo study combined free and Cipro-AZM-CS treated subgroups showed 100% mice survival with early resolution of infection and wound contraction (75%, 77.5% respectively) VS 45% for Cipro CS (P < 0.001). CONCLUSION: Combined free and Cipro-AZM-CS showed promising results in vitro and in vivo overcoming high resistance of biofilm producing P. aeruginosa.

Spectrum of Fungal Pathogens in Burn Wound Specimens: Data From a Tertiary Care Hospital Laboratory in Pakistan.

Burn patients are at great risk of developing fungal wound infections. Fungi are frequently cultured from burn tissue specimens alone or in combination with bacteria. However, the spectrum of fungi in burn patients from Pakistan has not been reported previously. A retrospective laboratory-based study was conducted and data on all positive cultures from burn wounds were included. During the study period, specimens were cultured on appropriate media and incubated for anaerobic and aerobic growth. Clinical and demographic information recorded during clinical reporting was also collected. Seventy tissue cultures were positive for microorganisms. Of these, 27 (39%) had growth of either filamentous mold (17 cases) or Candida species (14 cases). Two cases had growth of both mold and yeast. Aspergillus flavus was the most common mold (9) followed by Fusarium species (3). Candida tropicalis was the most common yeast (7) followed by Candida parapsilosis (4). There was concomitant bacterial growth in 19 cases, predominantly of Staphylococcus aureus (13), Pseudomonas aeruginosa (8), and other Gram-negative rods (6). Of the 35 patients in which treatment history was available, 33 were receiving broad-spectrum antibiotics. A high incidence of fungal isolation was seen in this study. Their findings are consistent with the global increase in fungal infections in burn wounds. High index of suspicion by clinicians and revision of culture protocols in burn patients may be warranted for optimal patient management.

High-Voltage, Pulsed Electric Fields Eliminate Pseudomonas aeruginosa Stable Infection in a Mouse Burn Model.

Objective: The incidence of severe infectious complications after burn injury increases mortality by 40%. However, traditional approaches for managing burn infections are not always effective. High-voltage, pulsed electric field (PEF) treatment shortly after a burn injury has demonstrated an antimicrobial effect in vivo; however, the working parameters and long-term effects of PEF treatment have not yet been investigated. Approach: Nine sets of PEF parameters were investigated to optimize the applied voltage, pulse duration, and frequency or pulse repetition for disinfection of Pseudomonas aeruginosa infection in a stable mouse burn wound model. The bacterial load after PEF administration was monitored for 3 days through bioluminescence imaging. Histological assessments and inflammation response analyses were performed at 1 and 24 h after the therapy. Results: Among all tested PEF parameters, the best disinfection efficacy of P. aeruginosa infection was achieved with a combination of 500 V, 100 µs, and 200 pulses delivered at 3 Hz through two plate electrodes positioned 1 mm apart for up to 3 days after the injury. Histological examinations revealed fewer inflammatory signs in PEF-treated wounds compared with untreated infected burns. Moreover, the expression levels of multiple inflammatory-related cytokines (interleukin [IL]-1α/ß, IL-6, IL-10, leukemia inhibitory factor [LIF], and tumor necrosis factor-alpha [TNF-α]), chemokines (macrophage inflammatory protein [MIP]-1α/ß and monocyte chemoattractant protein-1 [MCP-1]), and inflammation-related factors (vascular endothelial growth factor [VEGF], macrophage colony-stimulating factor [M-CSF], and granulocyte-macrophage colony-stimulating factor [G-CSF]) were significantly decreased in the infected burn wound after PEF treatment. Innovation: We showed that PEF treatment on infected wounds reduces the P. aeruginosa load and modulates inflammatory responses. Conclusion: The data presented in this study suggest that PEF treatment is a potent candidate for antimicrobial therapy for P. aeruginosa burn infections.

Active neutrophil responses counteract Candida albicans burn wound infection of ex vivo human skin explants.

Burn wounds are highly susceptible sites for colonization and infection by bacteria and fungi. Large wound surface, impaired local immunity, and broad-spectrum antibiotic therapy support growth of opportunistic fungi such as Candida albicans, which may lead to invasive candidiasis. Currently, it remains unknown whether depressed host defenses or fungal virulence drive the progression of burn wound candidiasis. Here we established an ex vivo burn wound model, where wounds were inflicted by applying preheated soldering iron to human skin explants, resulting in highly reproducible deep second-degree burn wounds. Eschar removal by debridement allowed for deeper C. albicans penetration into the burned tissue associated with prominent filamentation. Active migration of resident tissue neutrophils towards the damaged tissue and release of pro-inflammatory cytokine IL-1ß accompanied the burn. The neutrophil recruitment was further increased upon supplementation of the model with fresh immune cells. Wound area and depth decreased over time, indicating healing of the damaged tissue. Importantly, prominent neutrophil presence at the infected site correlated to the limited penetration of C. albicans into the burned tissue. Altogether, we established a reproducible burn wound model of candidiasis using ex vivo human skin explants, where immune responses actively control the progression of infection and promote tissue healing.

Thermo-responsive chitosan hydrogel for healing of full-thickness wounds infected with XDR bacteria isolated from burn patients: In vitro and in vivo animal model.

Treatment of non-healing skin wounds infected with extensively drug-resistant (XDR) bacteria remains as a big challenge. To date, different biomaterials have been applied for treatment of post-wound infections, nevertheless their efficacy for treatment of the wounds infected with XDR isolates has not been determined yet. In this study, the potential of the thermo-responsive chitosan (TCTS) hydrogel for protection of full-thickness wounds XDR bacteria isolated from burn patients was evaluated both in vitro and in vivo in a rat model. Antibacterial activity of the TCTS hydrogel against standard strain and clinical isolates of Acinetobacter baumannii, cytobiocompatibility for Hu02 fibroblast cells, degradation rate and swelling ratio were determined in vitro. MTT assay and disk diffusion test indicated no detectable cytotoxicity and antibacterial activity in vitro, respectively. In vivo study showed significant acceleration of wound healing, re-epithelialization, wound closure, and decreased colony count in the TCTS hydrogel group compared with control. This study suggests TCTS hydrogel as an excellent wound dressing for management of the wounds infected with XDR bacteria, and now promises to proceed with clinical investigations.

Burn Wound Microbiology and the Antibiotic Susceptibility Patterns of Bacterial Isolates in Three Burn Units of Abbottabad, Pakistan.

Infection is the leading cause of morbidity and mortality among burn patients and is accentuated multifold by the emergence of antimicrobial resistance among the nosocomial isolates. It is vital to know the common organisms involved in infected burn wound etiology and their respective antibiotic susceptibility patterns. These crucial findings can help in formulating a better and more efficient antimicrobial therapy plan for controlling burn wound infections. The current study was conducted to identify the common bacteria involved in causing infections in wounds of burn patients and their respective antibiotic susceptibility patterns in three hospitals of Abbottabad, Pakistan. A total of 100 patients were included from the burn units of three hospitals in Abbottabad. Wound swabs were taken from the deepest portions of infected burns, and the organisms involved were isolated via standard microbiological techniques. The Kirby-Bauer disc diffusion technique was used to monitor antibiotic susceptibility. Gram-positive organisms were found readily in infected burn wounds. Staphylococcus aureus (46%) was the most common isolate followed by Staphylococcus epidermidis (17%), Escherichia coli (16%), Proteus spp. (12%), Klebsiella pneumoniae (10%), and Pseudomonas aeruginosa, which was only 7%. Gram-positive bacteria were sensitive to amikacin, gentamicin, cefotaxime, and norfloxacin. In contrast, the gram-negative isolates were sensitive to amikacin, chloramphenicol, and nalidixic acid. Pseudomonas was resistant to most of the antibiotics tested in the present study.

Smart Hydrogel-Based DVDMS/bFGF Nanohybrids for Antibacterial Phototherapy with Multiple Damaging Sites and Accelerated Wound Healing.

Burn infection is one of the commonest causes of death in severely burned patients. Developing multifunctional biological nanomaterials has a great significance for the comprehensive treatment of burn infection. In this paper, we developed a hydrogel-based nanodelivery system with antibacterial activity and skin regeneration function, which was used for photodynamic antimicrobial chemotherapy (PACT) in the treatment of burns. The treatment system is mainly composed of porphyrin photosensitizer sinoporphyrin sodium (DVDMS) and poly(lactic-co-glycolic acid) (PLGA)-encapsulated basic fibroblast growth factor (bFGF) nanospheres that are embedded in carboxymethyl chitosan (CMCS)-sodium alginate to form CSDP hybrid hydrogel. We systematically evaluated the inherent antibacterial performance, rheological properties, fluorescence imaging, and biocompatibility of the CSDP nanosystem. Under mild photoirradiation (30 J/cm2, 5 min), 10 µg/mL CSDP showed excellent antibacterial and anti-biofilm activities, which eradicated almost 99.99% of Staphylococcus aureus and multidrug-resistant (MDR) S. aureus in vitro. KEGG analysis identified that multiple signaling pathways were changed in MDR S. aureus after PACT. In the burn-infection model, CSDP-PACT successfully inhibited bacteria growth and concurrently promoted wound healing. Moreover, several regenerative factors were increased and some proinflammatory factors were reduced in the burn wounds of CSDP hydrogel treatment. These results suggest that the multifunctional CSDP hydrogel is a portable, light-triggered, antibacterial theranostic-platform and CSDP-PACT provides a promising strategy or the mechanically based synergistic treatment of burn infections.

Silica microsphere-resorcinol composite embedded collagen scaffolds impart scar-less healing of chronic infected burns in type-I diabetic and non-diabetic rats.

The existence of diabetes and microbial infection in burn wounds makes the healing process more complex. Herein, we synthesize a collagen based hybrid scaffold incorporated with a silica-resorcinol composite and cross-linked with an oxidized fenugreek seed polysaccharide to stimulate scar-less healing in chronic wounds with type-I diabetes and microbial infection. The spectroscopic analyses of the hybrid scaffolds reveal the chemical and structural integrity of collagen. The hybrid scaffolds are shown to be appropriate for in vivo tissue regeneration through cytocompatibility and hemocompatibility studies. Scaffolds were applied to diabetic albino rats induced with chronically infected burn wounds with respective controls. Histological and immunohistochemical analyses of the granulation tissue collected from the hybrid scaffold treated animal groups showed improved angiogenesis, reepithelialization and TGF-ß3 expression, which eventually led to scar-less wound healing. The results confirm that the prepared hybrid collagen scaffold could be used for effective scar-less wound healing in chronic burn wounds.

Immediate Treatment of Burn Wounds with High Concentrations of Topical Antibiotics in an Alginate Hydrogel Using a Platform Wound Device.

Objective: There is an unmet need to improve immediate burn care, particularly when definitive treatment is delayed. Therefore, the purpose of this project was to formulate a hydrogel that contains very high concentrations of antibiotics and validate its use together with a platform wound device (PWD) for the immediate care of burns. Approach: The hydrogel properties were optimized by using a rheometer, differential scanning calorimetry, and liquid chromatography-mass spectrometry and were tested in an infected porcine burn model. Immediately, after burn creation, the burns were infected with different bacteria. Subsequently, the burns infected with Staphylococcus aureus, Pseudomonas aeruginosa, and Acinetobacter baumannii were covered with the PWD and treated with a single dose of hydrogel containing 1000 × minimum inhibitory concentration of vancomycin, gentamicin, and minocycline, respectively. On day 7 or 45, the animals were euthanized, and the burns were harvested for histology and quantitative bacteriology. Results: 0.625% was the best alginate concentration for the hydrogel in terms of viscosity, stability, and drug release. The porcine studies demonstrated that vancomycin-, gentamicin-, and minocycline-treated tissues contained significantly less bacteria and reduced depth of tissue necrosis in comparison to controls. Innovation: The PWD represents a platform technology that begins at the point of the first treatment by protecting the wound and allowing administration of topical therapeutics. The device can be adapted to enclose any size burn over any contour of the body. Conclusion: Antibiotics can be delivered safely in very high concentrations in a hydrogel using the PWD, and burn infections can be treated successfully with this method.

Metal ions and graphene-based compounds as alternative treatment options for burn wounds infected by antibiotic-resistant Pseudomonas aeruginosa.

Burn infections caused by Pseudomonas aeruginosa pose a major complication in wound healing. This study aimed to determine the antimicrobial effect of metal ions, graphene (Gr), and graphene oxide (GO), individually and in combination, against the planktonic and biofilm states of two antimicrobially resistant clinical strains of P. aeruginosa each with different antibiotic resistance profiles. Minimum inhibitory, minimum bactericidal, and fractional inhibitory concentrations were performed to determine the efficacy of the metal ions and graphene composites individually and their synergy in combination. Crystal violet biofilm and XTT assays measured the biofilm inhibition and metabolic activity, respectively. Molybdenum, platinum, tin, gold, and palladium ions exhibited the greatest antimicrobial activity (MIC = 7.8-26.0 mg/L), whilst GO and Gr demonstrated moderate-to-no effect against the planktonic bacterial cells, irrespective of their antibiograms. Biofilms were inhibited by zinc, palladium, silver, and graphene. In combination, silver-graphene and molybdenum-graphene inhibited both the planktonic and biofilm forms of the bacteria making them potential candidates for development into topical antimicrobials for burns patients infected with antibiotic-resistant P. aeruginosa.

Pharmacokinetics of meropenem in burn patients with infections caused by Gram-negative bacteria: Are we getting close to the right treatment?

OBJECTIVES: Infections caused by multidrug-resistant Gram-negative bacteria are associated with high mortality. A relevant concern is the efficacy of antibiotic therapy in burn patients in whom pathophysiological changes strongly influence pharmacokinetic (PK) parameters. This study aimed to describe the PK parameters of meropenem in a population of burn patients. METHODS: Blood samples were collected immediately before and 2 h and 5 h after the start of intravenous drug administration. Plasma meropenem concentrations were determined using an ultra-performance liquid chromatography-photodiode array method. RESULTS: Seventeen burn patients were enrolled in the study. Thirteen patients (76%) were treated with meropenem for infections byPseudomonas aeruginosa or Acinetobacter baumannii isolated from blood or wounds. Mean Cmax, Cmin, AUC0-24, half-life, drug clearance and volume of distribution were 28.9 mg/L, 3.7 mg/L, 280.2 mg h/L, 2.0 h, 19.0 L/h and 44.4 L, respectively. Six patients (35%) achieved a Cmin ≥3.3 mg/L and seven patients (41%) achieved a Cmax ≥ 28.4 mg/L, whilst nine patients (53%) achieved an AUC0-24 of >226 mg h/L. Given a minimum inhibitory concentration (MIC) of 0.5 mg/L, all patients satisfied the target AUC/MIC of >125, but when the MIC rises to 2 mg/L (the ECOFF), only five patients reached the desired AUC/MIC. Regarding fT>MIC at an MIC of 2 mg/L with a 2-h infusion time, 13 patients (76%) achieved the PK target (>75%). CONCLUSION: These data suggest that a combined 2-h infusion with a higher dosage of meropenem, including a loading dose, may be successful to achieve effective PK parameters.