High-Intensity Blue Light (450-460 nm) Phototherapy for Pseudomonas aeruginosa-Infected Wounds.

Background: Nosocomial wound infection with Pseudomonas aeruginosa (PA) is a serious complication often responsible for the septic mortality of burn patients. Objective: High-intensity antimicrobial blue light (aBL) treatment may represent an alternative therapy for PA infections and will be investigated in this study. Methods: Antibacterial effects of a light-emitting diode array (450-460 nm; 300 mW/cm2; 15/30 min; 270/540 J/cm2) against PA were determined by suspension assay, biofilm assay, and a human skin wound model and compared with 15-min topically applied 3% citric acid (CA) and wound irrigation solution (Prontosan®; PRT). Results: aBL reduced the bacterial number [2.51-3.56 log10 colony-forming unit (CFU)/mL], whereas PRT or CA treatment achieved a 4.64 or 6.60 log10 CFU/mL reduction in suspension assays. aBL reduced biofilm formation by 60-66%. PRT or CA treatment showed reductions by 25% or 13%. Here, aBL reduced bacterial number in biofilms (1.30-1.64 log10 CFU), but to a lower extend than PRT (2.41 log10 CFU) or CA (2.48 log10 CFU). In the wound skin model, aBL (2.21-2.33 log10 CFU) showed a bacterial reduction of the same magnitude as PRT (2.26 log10 CFU) and CA (2.30 log10 CFU). Conclusions: aBL showed a significant antibacterial efficacy against PA and biofilm formation in a short time. However, a clinical application of aBL in wound therapy requires effective active skin cooling and eye protection, which in turn may limit clinical implementation.

Assessment between antiseptic and normal saline for negative pressure wound therapy with instillation and dwell time in diabetic foot infections.

Negative pressure wound therapy with instillation and dwell time (NPWTi-d) is increasingly used for a diverse range of wounds. Meanwhile, the topical wound irrigation solution consisting of polyhexamethylene biguanide and betaine (PHMB-B) has shown efficacy in managing wound infections. However, the effectiveness of this solution as a topical instillation solution for NPWTi-d in patients with diabetic foot infections (DFIs) has not been thoroughly studied. The objective of this retrospective study was to evaluate the impact of using PHMB-B as the instillation solution during NPWTi-d on reducing bioburden and improving clinical outcomes in patients with DFIs. Between January 2017 and December 2022, a series of patients with DFIs received treatment with NPWTi-d, using either PHMB-B or normal saline as the instillation solution. Data collected retrospectively included demographic information, baseline wound characteristics, and treatment outcomes. The study included 61 patients in the PHMB-B group and 73 patients in the normal saline group, all diagnosed with DFIs. In comparison to patients treated with normal saline, patients with PHMB-B exhibited no significant differences in terms of wound bed preparation time (P = 0.5034), length of hospital stay (P = 0.6783), NPWTi-d application times (P = 0.1458), duration of systematic antimicrobial administration (P = 0.3567), or overall cost of hospitalization (P = 0.6713). The findings of the study suggest that the use of either PHMB-B or normal saline as an instillation solution in NPWTi-d for DFIs shows promise and effectiveness, yet no clinical distinction was observed between the two solutions.

Topical desiccating agent (DEBRICHEM): an accessible debridement option for removing biofilm in hard-to-heal wounds.

It is now assumed that all hard-to-heal wounds contain biofilm. Debridement plays a key role in wound-bed preparation, as it can remove biofilm along with the devitalised tissue, potentially leaving a clean wound bed that is more likely to progress towards healing. The gold standard methods of debridement (surgical and sharp) are the least used, as they require specialist training and are often not readily available at the point of need. Most other methods can be used by generalists but are slower. They all need regular applications. The topical desiccating agent DEBRICHEM is an innovative alternative, as it is fast, effective and can be used in all clinical settings, as well as typically requiring only a single use. This article describes best practice for achieving optimal outcomes with its use.

Current Knowledge and Perspectives of Phage Therapy for Combating Refractory Wound Infections.

Wound infection is one of the most important factors affecting wound healing, so its effective control is critical to promote the process of wound healing. However, with the increasing prevalence of multi-drug-resistant (MDR) bacterial strains, the prevention and treatment of wound infections are now more challenging, imposing heavy medical and financial burdens on patients. Furthermore, the diminishing effectiveness of conventional antimicrobials and the declining research on new antibiotics necessitate the urgent exploration of alternative treatments for wound infections. Recently, phage therapy has been revitalized as a promising strategy to address the challenges posed by bacterial infections in the era of antibiotic resistance. The use of phage therapy in treating infectious diseases has demonstrated positive results. This review provides an overview of the mechanisms, characteristics, and delivery methods of phage therapy for combating pathogenic bacteria. Then, we focus on the clinical application of various phage therapies in managing refractory wound infections, such as diabetic foot infections, as well as traumatic, surgical, and burn wound infections. Additionally, an analysis of the potential obstacles and challenges of phage therapy in clinical practice is presented, along with corresponding strategies for addressing these issues. This review serves to enhance our understanding of phage therapy and provides innovative avenues for addressing refractory infections in wound healing.

Improving wound infection management: education and evaluation of an infection management pathway.

OBJECTIVE: To assess the clinical impact and acceptance of an infection management (IM) pathway, designed to improve the consistency of care of wound infection when introduced, and supported by an educational programme. METHOD: An education and evaluation programme (T3 programme) was-conducted in Portugal, Spain and Italy. This consisted of a two-hour educational, virtual seminar, followed by a four-week evaluation of an IM pathway during which survey data were collected on the impact of this pathway on clinician-selected patients. Finally, all participants reconvened for a virtual meeting during which the combined results were disseminated. The pathway provided guidance to clinicians regarding the targeted use of antimicrobial wound dressings according to the presence and absence of signs and symptoms of wound infection. RESULTS: Responses relating to 259 patients treated according to the IM pathway, 139 (53.7%) of whom had received previous antimicrobial treatment, were captured. Signs and symptoms of infection resolved within four weeks of treatment in >90% of patients. All 25 patients who had received prior antimicrobial treatment for ≥3 months experienced a resolution in the signs and symptoms of infection within four weeks. The majority of participating clinicians agreed that the IM pathway improved decision-making (94.9%) and confidence (97.3%), and helped to determine the correct antimicrobial treatment (91.4%) in the context of wound infection. CONCLUSION: The T3 programme was an efficient way to deliver a structured educational programme. The use of the IM pathway resulted in >90% of patients achieving resolution of their signs and symptoms of wound infection.

The use of custom-made negative pressure wound therapy to manage acute wound infections: a retrospective outcomes study.

BACKGROUND: NPWT has been used to treat various wounds. Scant evidence exists on the use of custom-made NPWT for infected wounds. NPWT dressings promote wound healing by increasing local blood flow and antibiotic concentration, and by removing exudates from the wound. OBJECTIVE: To report the use of custom-made NPWT dressings to manage complex infected wounds of the lower limb. MATERIALS AND METHODS: The authors retrospectively reviewed the records of 43 patients with complex infected wounds of the lower limb treated with debridement and low-cost, custom-made NPWT dressing connected to wall suction from January 1, 2018 to December 31, 2020, at PSG Medical College Hospital, Coimbatore, India. RESULTS: A total of 43 patients with infected wounds of the lower limb were treated with the custom-made NPWT dressings. Second-look debridement was required in 5 patients. An average of 5 dressing changes were required for optimal wound granulation, with 23% of patients (n = 10) requiring secondary suturing and 62% (n = 27) requiring STSG for definitive coverage of the wound. Healing by secondary intention was achieved in 6 patients. The average duration from the start of therapy until the wound was ready for coverage (STSG or secondary suturing) was 2.5 weeks (range, 1-5 weeks), with an average time to complete wound healing of 5 weeks (range, 3-7 weeks). The most common wound isolate was Staphylococcus aureus (60%). No complications occurred. CONCLUSIONS: Custom-made NPWT dressings are safe to use in complex infected lower limb wounds. These dressings keep the wound dry and promote healing. Wound debridement followed by NPWT combined with antibiotic therapy can act synergistically to promote wound healing and control infection.

Effect of quality nursing intervention on wound healing in patients with burns: A meta-analysis.

This meta-analysis aimed to explore the effects of quality nursing intervention on wound healing in patients with burns. A computerised search was conducted for randomised controlled trials (RCTs) on the effect of quality nursing intervention on wound healing in patients with burns in the PubMed, Embase, Google Scholar, Cochrane Library, China National Knowledge Infrastructure and Wanfang databases from the date of database inception to November 2023. Two researchers independently screened the literature, extracted data and performed quality assessment based on the inclusion and exclusion criteria. Stata 17.0 software was used for the data analysis. Twenty-nine RCTs involving 2637 patients with burns were included. The meta-analysis revealed that compared with conventional nursing, the implementation of quality nursing intervention in patients with burns significantly shortened the wound healing time (standardised mean difference [SMD] = -2.93, 95% confidence interval [CI]: -3.44 to -2.42, p < 0.001). The incidence of wound infections (odds ratio [OR] = 0.14, 95% CI: 0.07-0.27, p < 0.001) and complications (OR = 0.16, 95% CI: 0.11-0.23, p < 0.001) was also reduced significantly. This meta-analysis shows that applying quality nursing interventions in patients with burns can significantly shorten the wound healing time and reduce the incidence of wound infection and complications, thus promoting early patient recovery.

Negative pressure wound therapy with instillation and dwell time in debridement of fibrinous leg ulcers.

OBJECTIVE: In conjunction with appropriate wound care, negative pressure wound therapy with instillation and dwell time (NPWTi-d) may be used as an adjunct therapy for acute or hard-to-heal (chronic) wounds, especially when infected. However, there are very few data on the use of NPWTi-d in the treatment of fibrinous wounds that are difficult to debride mechanically. The main objective of this study was to describe changes in the fibrin area of such wounds, before and after treatment with NPWTi-d. METHOD: This was a monocentric, observational, prospective pilot study evaluating the NPWTi-d medical device. Eligible patients included in the study were those with hard-to-heal lower limb ulcers who had previously undergone unsuccessful specific debridement treatment for their wound, with failure of manual mechanic debridement for at least six weeks' duration, and whose wounds had a fibrinous surface area of >70% of the total wound surface area. The primary endpoint was the difference in the percentage of fibrinous surface area before and after treatment. RESULTS: A total of 14 patients who received treatment for lower limb ulcers between October 2017 and August 2019 were included in the study. There was a significant shrinkage rate of the fibrinous wound surface between the start and end of treatment (83.6±14.5% and 32.2±19.7%, respectively; p<0.001). CONCLUSION: This study showed a significant decrease in fibrin area in wounds treated with NPWTi-d, with good tolerance. We believe that NPWTi-d has its place in the multidisciplinary management of patients with hard-to-heal ulcers. Additional randomised studies are required to confirm these findings. DECLARATION OF INTEREST: The authors have no conflicts of interest.

Cytotoxicity and concentration of silver ions released from dressings in the treatment of infected wounds: a systematic review.

Introduction: Silver-releasing dressings are used in the treatment of infected wounds. Despite their widespread use, neither the amount of silver released nor the potential in vivo toxicity is known. The aim of this study was to evaluate the cytotoxic effects and the amount of silver released from commercially available dressings with infected wounds. Methods: The review was conducted according to the PRISMA statement. The Web of Science, PubMed, Embase, Scopus, and CINAHL databases were searched for studies from 2002 through December 2022. The criteria were as follows: population (human patients with infected wounds); intervention (commercial dressings with clinical silver authorized for use in humans); and outcomes (concentrations of silver ions released into tissues and plasma). Any study based on silver-free dressings, experimental dressings, or dressings not for clinical use in humans should be excluded. According to the type of study, systematic reviews, experimental, quasi-experimental, and observational studies in English, Spanish, or Portuguese were considered. The quality of the selected studies was assessed using the JBI critical appraisal tools. Studies that assessed at least 65% of the included items were included. Data were extracted independently by two reviewers. Results: 740 articles were found and five were finally selected (all of them quasi-experimental). Heterogeneity was found in terms of study design, application of silver dressings, and methods of assessment, which limited the comparability between studies. Conclusion: In vivo comparative studies of clinical dressings for control of infection lack a standardized methodology that allows observation of all the variables of silver performance at local and systemic levels, as well as evaluation of its cytotoxicity. It cannot be concluded whether the assessed concentrations of released silver in commercial dressings for the topical treatment of infected wounds are cytotoxic to skin cells. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022351041, PROSPERO [CRD42022351041].

From hemostasis to proliferation: Accelerating the infected wound healing through a comprehensive repair strategy based on GA/OKGM hydrogel loaded with MXene@TiO2 nanosheets.

The treatment of infected wounds poses a formidable challenge in clinical practice due to the detrimental effects of uncontrolled bacterial infection and excessive oxidative stress, resulting in prolonged inflammation and impaired wound healing. In this study, we presented a MXene@TiO2 (MT) nanosheets loaded composite hydrogel named as GA/OKGM/MT hydrogel, which was formed based on the Schiff base reaction between adipic dihydrazide modified gelatin (GA)and Oxidized Konjac Glucomannan (OKGM), as the wound dressing. During the hemostasis phase, the GA/OKGM/MT hydrogel demonstrated effective adherence to the skin, facilitating rapid hemostasis. In the subsequent inflammation phase, the GA/OKGM/MT hydrogel effectively eradicated bacteria through MXene@TiO2-induced photothermal therapy (PTT) and eliminated excessive reactive oxygen species (ROS), thereby facilitating the transition from the inflammation phase to the proliferation phase. During the proliferation phase, the combined application of GA/OKGM/MT hydrogel with electrical stimulation (ES) promoted fibroblast proliferation and migration, leading to accelerated collagen deposition and angiogenesis at the wound site. Overall, the comprehensive repair strategy based on the GA/OKGM/MT hydrogel demonstrated both safety and reliability. It expedited the progression through the hemostasis, inflammation, and proliferation phases of wound healing, showcasing significant potential for the treatment of infected wounds.

The efficacy and safety of non-surgical treatment of diabetic foot wound infections and ulcers: A systemic review and meta-analysis.

This meta-analysis evaluates the efficacy and safety of non-surgical treatments for diabetic foot ulcers and infections. After a rigorous literature review, seven studies were selected for detailed analysis. The findings demonstrate that non-surgical treatments significantly reduce wound infection rates (standardized mean difference [SMD] = -15.15, 95% confidence interval [CI]: [-19.05, -11.25], p < 0.01) compared to surgical methods. Ulcer healing rates were found to be comparable between non-surgical and surgical approaches (SMD = 0.07, 95% CI: [-0.38, 0.51], p = 0.15). Importantly, the rate of amputations within 6 months post-treatment was significantly lower in the non-surgical group (risk ratio [RR] = 0.19, 95% CI: [0.09, 0.41], p < 0.01). Additionally, a lower mortality rate was observed in patients treated non-surgically (RR = 0.28, 95% CI: [0.13, 0.59], p < 0.01). These results affirm the effectiveness and safety of non-surgical interventions in managing diabetic foot ulcers, suggesting that they should be considered a viable option in diabetic foot care.

Biofilm therapy for chronic wounds.

Chronic wounds have been a major factor of serious harm to global public health. At present, it is known that almost all chronic wounds contain biofilms, which seriously hinder the healing process. Removal of biofilms can effectively promote the healing of chronic wounds. As the study of wound biofilms deepens, many new treatment methods have emerged, thus bringing revolutionary means for the treatment of chronic wound biofilm. This review summarizes various methods for the treatment of chronic wound biofilm worldwide to provide a theoretical summary and practical basis for the selection of suitable wound biofilm treatment methods in clinical practice.

Negative Pressure Wound Therapy With and Without Instillation in Necrotizing Soft Tissue Infections.

Background: Necrotizing soft tissue infections (NSTIs) are rare but deadly infections that require early and often extensive surgical debridement. After debridement, patients frequently have substantial morbidity because of large, open wounds. Hypothesis: Negative pressure wound therapy with instillation (NPWTi) results in higher wound closure rates compared with traditional negative pressure wound therapy (NPWT) or wet to dry dressings (moist wound care dressing). Patients and Methods: A prospectively maintained Acute and Critical Care Surgery database spanning 2008-2018 was queried for patients with a diagnosis of necrotizing fasciitis, Fournier gangrene, or gas gangrene. Data were collected on patient comorbidities, operative management, and clinical outcomes. Patients were stratified by use of moist wound care dressing, traditional NPWT, or NPWTi. Data were analyzed using analysis of variance (ANOVA), χ2, and logistic regression. Results: During the 10-year study period, patients were treated for NSTI; 173 were managed with moist wound care dressing, 150 with NPWT, and 48 with NPWTi. Patients were similar in terms of demographics, body mass index (BMI), diabetes mellitus, and smoking rates. Overall, complication rates were not substantially different, but mortality was higher in the moist wound care dressing group (16.2% vs. 10.7% NPWT vs. 2.1% NPWTi; p = 0.02). In the moist wound care dressing group, 81.5% of patients had an open wound at discharge compared with 52.7% of the NPWT group and only 14.6% of the NPWTi group (p < 0.001). On multivariable regression, NPWTi was associated with closure rates five times higher than the NPWT group (odds ratio [OR], 5.28; 95% confidence interval [CI], 2.40-11.61; p < 0.001) after controlling for smoking status, intravenous drug use, number of operations, and involvement of the most common region of the body. Conclusions: Negative pressure wound therapy with instillation is associated with higher rates of wound closure without increasing complication rates in patients with NSTI compared with traditional NPWT or moist wound care dressing. Although prospective studies are needed, this indicates the potential to improve patient quality of life through reduced pain and outpatient home health needs.

Safety and efficacy of a phage cocktail on murine wound infections caused by carbapenem-resistant Klebsiella pneumoniae.

OBJECTIVES: Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a leading pathogen causing difficult-to-treat, healthcare-associated wound infections. Phages are an alternative approach against CRKP. This study established murine wound infection models with a CRKP clinical strain of sequence type 11 and capsular type KL64, which is the dominant type in China, carrying genes encoding KPC-2 and NDM-1 carbapenemases. METHODS: A cocktail was made comprising three lytic phages of different viral families against the strain. The phage cocktail restricted bacterial growth for 10 hours in vitro. The efficacy and safety of the phage cocktail in treating a murine wound CRKP infection were then evaluated. Mice were randomly assigned into four groups (16 for each) comprising a phage treatment group, infected with bacteria and 30 minutes later with phages, and three control groups administered with PBS (negative control), bacteria (infection control), or phages (phage control) on the wound. Wound tissues were processed for counting bacterial loads on days 1, 3, and 7 post-infection and examined for histopathological change on days 3 and 7. Two remaining mice in each group were monitored for wound healing until day 14. RESULTS: Compared with the infection control group, the wound bacterial load in the phage treatment group decreased by 4.95 × 102 CFU/g (> 100-fold; P < 0.05) at day 7 post-treatment, and wounds healed on day 10, as opposed to day 14 in the infection control group. No adverse events associated with phages were observed. CONCLUSION: The phage cocktail significantly reduced the wound bacterial load and promoted wound healing with good safety.

Intelligent wound dressing for simultaneous in situ detection and elimination of pathogenic bacteria.

Wound infections hinder the healing process and potentially result in life-threatening complications, which urgently require rapid and timely detection and treatment pathogens during the early stages of infection. Here, an intelligent wound dressing was developed to enable in situ detection and elimination of pathogenic bacteria through a combination of point-of-care testing and antibacterial photodynamic therapy technology. The dressing is an injectable hydrogel composed of carboxymethyl chitosan and oxidized sodium alginate, with addition of 4-methylumphulone beta-D-glucoside (MUG) and up-converted nanoparticles coated with titanium dioxide (UCNPs@TiO2). The presence of bacteria can be visually detected by monitoring the blue fluorescence of 4-methylumbellione, generated through the reaction between MUG and the pathogen-associated enzyme. The UCNPs@TiO2 photosensitizers were synthesized and demonstrated high antibacterial activity through the generation of reactive oxygen species when exposed to near-infrared irradiation. Meanwhile, a smartphone-based portable detection system equipped with a self-developed Android app was constructed for in situ detection of pathogens in mere seconds, detecting as few as 103 colony-forming unit. Additionally, the dressing was tested in a rat infected wound model and showed good antibacterial activity and pro-healing ability. These results suggest that the proposed intelligent wound dressing has potential for use in the diagnosis and management of wound infections. STATEMENT OF SIGNIFICANCE: An intelligent wound dressing has been prepared for simultaneous in situ detection and elimination of pathogenic bacteria. The presence of bacteria can be visually detected by tracking the blue fluorescence of the dressing. Moreover, a smartphone-based detection system was constructed to detect and diagnose pathogenic bacteria before reaching the infection limit. Meanwhile, the dressing was able to effectively eliminate key pathogenic bacteria on demand through antibacterial photodynamic therapy under NIR irradiation. The proposed intelligent wound dressing enables timely detection and treatment of infectious pathogens at an early stage, which is beneficial for wound management.

Bacteriophage Treatment of Infected Diabetic Foot Ulcers.

Diabetic foot ulcers occur as a common complication of diabetes. The concomitant infection significantly delays the healing of the ulcers. Antibiotic treatment of infected ulcers is complicated by the formation of microbial biofilms, which are often heterogeneous and resistant to antibiotics. Bacteriophage therapy is considered an additional approach to the treatment of infected wounds. Here, we describe the basic method of application of bacteriophages for the treatment of infected diabetic foot ulcers, including very large ones.

Potential antibacterial activity and healing effect of topical administration of bone marrow and adipose mesenchymal stem cells encapsulated in collagen-fibrin hydrogel scaffold on full-thickness burn wound infection caused by Pseudomonas aeruginosa.

Burns injuries are prone to hospital-acquired infections, and Pseudomonas aeruginosa is one of the most common causes of mortality and morbidity in patients with burn injuries. Thus, this study aimed to analyze the effects of topical treatment with bone marrow (BM-MSC) and adipose mesenchymal stem cells (AD-MSC) encapsulated in collagen and fibrin scaffolds in a Balb/c model of burn wound infection. Extraction of stem cells from adipose and bone marrow tissue of rats was performed and cells were characterized using standard methods. Then, collagen, fibrin and collagen-fibrin scaffolds were constructed and the extracted cells were encapsulated in all three scaffolds. Then, 3rd degree burn was induced in mice and 1.5 × 108 (CFU/ml) of P. aeruginosa was introduced to the burn wound. Subsequently, after 24 h of inducing wound infection, encapsulated MSCs were introduced as dressings to burn wound infection and microbial load as well as rate of wound infection healing was measured. The results of this study showed that the use of BM-MSC and AD-MSC encapsulated in collagen-fibrin scaffold reduced the bacteria load down to 54 and 21 CFU/gr, respectively (P < 0.05). Moreover, BM-MSC and AD-MSC encapsulated in collagen-fibrin showed 80% and 75% wound healing, respectively (P < 0.05). Also, we found no significant between cell origin and healing. Encapsulation of MSCs into collagen-fibrin scaffolds could be effective not only against P. aeruginosa infection, but also healing and regeneration of burn wound.

Development and use of a porcine model with clinically relevant chronic infected wounds.

Chronic ischemic wounds affect millions of people causing significant pain and disability. They can be considered to be stalled in the inflammatory stage and cannot heal without additional measures. A valid animal model is necessary to evaluate the efficacy of topical wound healing therapies and wearable technologies. A porcine model, although higher in cost, maintenance, and space requirements, is superior to the commonly used rodent or rabbit model for wound healing. Previous studies have shown that pig wounds have greater similarity to human wounds in responses to a variety of treatments, including wound dressings and antibiotics. The current study created a porcine model of large chronic wounds to assess a wearable electroceutical technology, with monitoring of healing variables and infection. Electroceutical therapy is the only adjunctive treatment recommended for chronic wound therapy. A porcine model of large chronic wounds of clinically realistic size was created and utilized to evaluate a wearable electroceutical biotechnology. Multivariate non-invasive assessment was used to monitor wound progression over multiple timepoints. Outcomes suggest that a wearable electrostimulation bandage, has the potential to offer therapeutic benefit in human wounds. The tested wearable device provides the same proven effectiveness of traditional electroceutical therapy while mitigating commonly cited barriers, including substantial time requirements, and availability and complexity of currently available equipment, preventing its implementation in routine wound care. The model is also appropriate for evaluation of other wearables or topical therapeutics.