GENERAL PURPOSETo review the therapeutic indices of topical antiseptics for bacterial species commonly isolated from chronic wounds.TARGET AUDIENCEThis continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care.LEARNING OBJECTIVES/OUTCOMESAfter participating in this educational activity, the participant will:1. Explain the mechanisms underlying chronic wound physiology and their implications for effective wound healing and management.2. Evaluate the role of therapeutic index values for topical antiseptics in chronic wound management.3. Apply evidence-based treatment strategies for chronic wound management.LEARNING OBJECTIVES/OUTCOMESAfter participating in this educational activity, the participant will:1. Explain the mechanisms underlying chronic wound physiology and their implications for effective wound healing and management.2. Evaluate the role of therapeutic index values for topical antiseptics in chronic wound management.3. Apply evidence-based treatment strategies for chronic wound management.LEARNING OBJECTIVES/OUTCOMESAfter participating in this educational activity, the participant will:1. Explain the mechanisms underlying chronic wound physiology and their implications for effective wound healing and management.2. Evaluate the role of therapeutic index values for topical antiseptics in chronic wound management.3. Apply evidence-based treatment strategies for chronic wound management.LEARNING OBJECTIVES/OUTCOMESAfter participating in this educational activity, the participant will:1. Explain the mechanisms underlying chronic wound physiology and their implications for effective wound healing and management.2. Evaluate the role of therapeutic index values for topical antiseptics in chronic wound management.3. Apply evidence-based treatment strategies for chronic wound management. BACKGROUNDChronic wounds place a heavy burden on healthcare systems and reduce patients' activities of daily living. Increased bacterial bioburden (local infection, covert infection) impairs wound healing. With increased antimicrobial resistance, alternative antimicrobial strategies are important.OBJECTIVETo determine the topical antiseptic therapeutic index values for common wound bacterial species. The therapeutic index is a ratio comparing lowest concentration that causes mammalian cell cytotoxicity to the minimum bactericidal concentration; higher values indicate greater safety / clinical benefit.DATA SOURCESMEDLINE and EMBASE databases were searched from conception to June 2023. Common wound bacterial species and their in-vitro minimum bactericidal concentrations were compared to the minimum mammalian cell cytotoxicity concentration.STUDY SELECTIONThe authors identified 37 qualifying articles.DATA EXTRACTIONAntiseptic, bacterial organism, mammalian cell type, minimum bactericidal concentration, and mammalian cell cytotoxicity concentration values.DATA SYNTHESISThe therapeutic indices for the topical antiseptics were generally low, with most ranging between 0.5 and 3.0. The highest therapeutic index values for Escherichia coli (5.49), Staphylococcus aureus (6.31) and Pseudomonas aeruginosa (8.81) were achieved by hypochlorous acid. The highest therapeutic index value for methicillin resistant S aureus (12.1) was achieved by polyhexamethylene biguanide.CONCLUSIONSAntibiotic stewardship principles need to be applied to topical antiseptics due to some isolated topical antiseptic resistance and cross-resistance to oral antimicrobials. The choice of antiseptic should not be made solely based on therapeutic index values but individualized with the wound healing condition including covert infection.

Slough is a well-known feature of non-healing wounds. This pilot study aims to determine the proteomic and microbiologic components of slough as well as interrogate the associations between wound slough components and wound healing. Ten subjects with slow-to-heal wounds and visible slough were enrolled. Aetiologies included venous stasis ulcers, post-surgical site infections and pressure ulcers. Patient co-morbidities and wound healing outcome at 3-months post-sample collection was recorded. Debrided slough was analysed microscopically, through untargeted proteomics, and high-throughput bacterial 16S-ribosomal gene sequencing. Microscopic imaging revealed wound slough to be amorphous in structure and highly variable. 16S-profiling found slough microbial communities to associate with wound aetiology and location on the body. Across all subjects, slough largely consisted of proteins involved in skin structure and formation, blood-clot formation and immune processes. To predict variables associated with wound healing, protein, microbial and clinical datasets were integrated into a supervised discriminant analysis. This analysis revealed that healing wounds were enriched for proteins involved in skin barrier development and negative regulation of immune responses. While wounds that deteriorated over time started off with a higher baseline Bates-Jensen Wound Assessment Score and were enriched for anaerobic bacterial taxa and chronic inflammatory proteins. To our knowledge, this is the first study to integrate clinical, microbiome, and proteomic data to systematically characterise wound slough and integrate it into a single assessment to predict wound healing outcome. Collectively, our findings underscore how slough components can help identify wounds at risk of continued impaired healing and serves as an underutilised biomarker.

Objective: The effect of continuous topical oxygen therapy (cTOT) on Pseudomonas aeruginosa biofilm gene transcription profiles following inoculation onto porcine skin, using a customised molecular assay was determined. Method: Sterilised porcine skin explants were inoculated with Pseudomonas aeruginosa in triplicate: 0 hours as negative control; 24 hours cTOT device on; 24 hours cTOT device off. The oxygen delivery system of the cTOT device was applied to the inoculated tissue and covered with a semi-occlusive dressing. All samples were incubated at 37±2°C for 24 hours, with the 0 hours negative control inoculated porcine skin samples recovered immediately. Planktonic suspensions and porcine skin biopsy samples were taken at 0 hours and 24 hours. Samples were processed and quantifiably assessed using gene specific reverse transcription-quantitative polymerase chain reaction assays for a panel of eight Pseudomonas aeruginosa genes (16S, pelA, pslA, rsaL, pcrV, pscQ, acpP, cbrA) associated with biofilm formation, quorum sensing, protein secretion/translocation and metabolism. Results: Transcriptional upregulation of pelA, pcrV and acpP, responsible for intracellular adhesion, needletip protein production for type-3 secretion systems and fatty acid synthesis during proliferation, respectively, was observed when the cTOT device was switched on compared to when the device was switched off. Data suggest increased metabolic activity within bacterial cells following cTOT treatment. Conclusion: cTOT is an adjunctive therapy that supports faster healing and pain reduction in non-healing hypoxic wounds. Oxygen has previously been shown to increase susceptibility of biofilms to antibiotics through enhancing metabolism. Observed gene expression changes highlighted the impact of cTOT on biofilms, potentially influencing antimicrobial treatment success in wounds. Further in vitro and clinical investigations are warranted.

ABSTRACT GENERAL PURPOSE To review a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. TARGET AUDIENCE This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and registered nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES After participating in this educational activity, the participant will: 1. Summarize issues related to wound assessment. 2. Identify a class of drugs for the treatment of type II diabetes mellitus that has been shown to improve glycemia, nephroprotection, and cardiovascular outcomes. 3. Synthesize strategies for wound management, including treatment in resource-limited settings. 4. Specify the target time for edge advancement in chronic, healable wounds. BACKGROUND Chronic wound management in low-resource settings deserves special attention. Rural or underresourced settings (ie, those with limited basic needs/healthcare supplies and inconsistent availability of interprofessional team members) may not have the capacity to apply or duplicate best practices from urban or abundantly-resourced settings. OBJECTIVE The authors linked world expertise to develop a practical and scientifically sound application of the wound bed preparation model for communities without ideal resources. METHODS A group of 41 wound experts from 15 countries reached a consensus on wound bed preparation in resource-limited settings. RESULTS Each statement of 10 key concepts (32 substatements) reached more than 88% consensus. CONCLUSIONS The consensus statements and rationales can guide clinical practice and research for practitioners in low-resource settings. These concepts should prompt ongoing innovation to improve patient outcomes and healthcare system efficiency for all persons with foot ulcers, especially persons with diabetes.

The presence of microbial biofilms in many human chronic wounds led to the hypothesis that biofilms delay healing of these wounds. We tested this hypothesis in a population of 117 older individuals with venous leg ulcers who were receiving standardised therapy, including frequent debridement. Debridement specimens were analysed for the amount of bacterial biomass by two independent methods: a microscopic approach that scored the relative size and number of bacterial aggregates, interpreted as a biofilm metric, and conventional enumeration by agar plating for viable bacteria. The plating protocol yielded three distinct values: the total viable bacterial count, bleach-tolerant bacteria, and the log reduction in viable bacteria upon bleach treatment. Wound healing rates over an 8-week observation period were calculated as the rate of decrease of the equivalent diameter of the wound. There was no statistically significant association between wound healing and the biofilm metric in any of the three analyses performed (p ≥0.15). In all three statistical tests, wound healing was associated with the log reduction caused by bleach treatment (p ≤0.004); wounds that harboured bacteria that were more bleach-susceptible healed more slowly. A refinement of the model of chronic wound infection pathogenesis is proposed in which dormant bacteria constitute a persistent nidus and outgrowth of metabolically active cells impairs healing. This model constitutes a new hypothesis as metabolic activity was not directly measured in this investigation.

Background Nitric oxide (NO) plays a critical role in wound healing, including stimulating vasodilation, angiogenesis and broad antimicrobial activity.

Background Nitric oxide (NO) plays critical roles in wound healing, including stimulating vasodilation, angiogenesis and broad antimicrobial activity.

Significance: The Wound Healing Foundation recognized the need for consensus-based unbiased recommendations for the treatment of wounds. As a first step, a consensus on the treatment of chronic wounds was developed and published in 2022. The current publication on acute wounds represents the second step in this process. Acute wounds may result from any number of conditions, including burns, military and combat operations, and trauma to specific areas of the body. The management of acute wounds requires timely and evidence-driven intervention to achieve optimal clinical outcomes. This consensus statement provides the clinician with the necessary foundational approaches to the causes, diagnosis, and therapeutic management of acute wounds. Presented in a structured format, this is a useful guide for clinicians and learners in all patient care settings.Recent Advances: Recent advances in the management of acute wounds have centered on stabilization and treatment in the military and combat environment. Specifically, advancements in hemostasis, resuscitation, and the mitigation of infection risk through timely initiation of antibiotics and avoidance of high-pressure irrigation in contaminated soft tissue injury.Critical Issues: Critical issues include infection control, pain management, and the unique considerations for the management of acute wounds in pediatric patients.Future Directions: Future directions include new approaches to preventing the progression and conversion of burns through the use of specific gel formulations. Additionally, the use of three-dimensional bioprinting and photo-modulation for reconstruction is a promising area for continued discovery.

Slough is a well-known feature of non-healing wounds. This study aims to determine the proteomic and microbiologic components of slough as well as interrogate the associations between wound slough components and wound healing. Twenty-three subjects with slow-to-heal wounds and visible slough were enrolled. Etiologies included venous stasis ulcers, post-surgical site infections, and pressure ulcers. Patient co-morbidities and wound healing outcome at 3-months post-sample collection was recorded. Debrided slough was analyzed microscopically, through untargeted proteomics, and high-throughput bacterial 16S-ribosomal gene sequencing. Microscopic imaging revealed wound slough to be amorphous in structure and highly variable. 16S-profiling found slough microbial communities to associate with wound etiology and location on the body. Across all subjects, slough largely consisted of proteins involved in skin structure and formation, blood-clot formation, and immune processes. To predict variables associated with wound healing, protein, microbial, and clinical datasets were integrated into a supervised discriminant analysis. This analysis revealed that healing wounds were enriched for proteins involved in skin barrier development and negative regulation of immune responses. While wounds that deteriorated over time started off with a higher baseline Bates-Jensen Wound Assessment Score and were enriched for anerobic bacterial taxa and chronic inflammatory proteins. To our knowledge, this is the first study to integrate clinical, microbiome, and proteomic data to systematically characterize wound slough and integrate it into a single assessment to predict wound healing outcome. Collectively, our findings underscore how slough components can help identify wounds at risk of continued impaired healing and serves as an underutilized biomarker.

OBJECTIVE:The antimicrobial effects of a borate-based bioactive glass matrix (BBBGM) on clinically relevant microorganisms was investigated for up to seven days in vitro.METHOD:A total of 19 wound-relevant pathogens were studied using the in vitro AATCC 100 test method.RESULTS:The reduction of viable Gram-negative and Gram-positive bacteria and yeasts at days 4 and 7 post-culture on the BBBGM was significant (> 4log10) in most cases. Mould counts were reduced (<2log10) during the seven-day assessment, indicating that mould viability and reproduction was inhibited. The cell count of each organism was reduced at seven days indicating that the BBBGM not only reduced the viable cell count, but that the cell count did not recover during the seven-day period, indicating a sustained reduction in pathogenic activity.CONCLUSION:Based on the present results, the use of a BBBGM as a pathogenic barrier should be considered as a tool for combating pathogenic colonisation and infection in acute and hard-to-heal (chronic) wounds.

Solutions containing Ag0 nanoclusters, Ag+1, and higher oxidation state silver, generated from nanocrystalline silver dressings, were anti-inflammatory against porcine skin inflammation. The dressings have clinically-demonstrated broad-spectrum antimicrobial activity, suggesting application of nanosilver solutions in treating pulmonary infection. Nanosilver solutions were tested for antimicrobial efficacy; against HSV-1 and SARS-CoV-2; and nebulized in rats with acute pneumonia. Patients with pneumonia (ventilated), fungal sinusitis, burns plus COVID-19, and two non-hospitalized patients with COVID-19 received nebulized nanosilver solution. Nanosilver solutions demonstrated pH-dependent antimicrobial efficacy; reduced infection and inflammation without evidence of lung toxicity in the rat model; and inactivated HSV-1 and SARS-CoV-2. Pneumonia patients had rapidly reduced pulmonary symptoms, recovering pre-illness respiratory function. Fungal sinusitis-related inflammation decreased immediately with infection clearance within 21 days. Non-hospitalized patients with COVID-19 experienced rapid symptom remission. Nanosilver solutions, due to anti-inflammatory, antiviral, and antimicrobial activity, may be effective for treating respiratory inflammation and infections caused by viruses and/or microbes.

Human epithelia are constantly exposed to microorganisms present in the environment or residing as part of commensal flora. Despite this exposure, infections involving the skin and subcutaneous tissue in healthy individuals are, fortunately, quite rare. Many of the wounds that afflict the human body occur in individuals of ill health and/or where the mechanism of wounding is impeded by host immunological, physiological or regenerative dysfunction. The interplay between microorganisms and host immunity is complex and remains ill defined; however, the interpretation of downstream manifestations of the host response to invading microorganisms is still based largely on the clinical signs and symptoms of an active infectious process. In this review article we will provide a brief overview of the current challenges clinicians face in diagnosing wound infections, how chronic infections caused by biofilms are a major challenge, and how there have been minimal advancements in developing new diagnostics or therapeutics in the identification and management of wound infections.

Wound infection is a major challenge for clinicians globally, with accurate and timely identification of wound infection being critical to achieving clinical and cost-effective management, and promotion of healing. This paper presents an overview of the development of the International Wound Infection Institute (IWII)'s 2022 Wound Infection in Clinical Practice consensus document. The updated document summarises current evidence and provides multidisciplinary healthcare providers with effective guidance and support on terminology, paradigms related to biofilm, identification of wound infection, wound cleansing, debridement and antimicrobial stewardship. Integral to the update is revision of wound infection management strategies which are incorporated within the IWII's Wound Infection Continuum (IWII-WIC) and management plan. The aim of the 2022 IWII consensus document update was to provide an accessible and useful clinical resource in at least six languages, incorporating the latest evidence and current best practice for wound infection and prevention. Dissemination techniques for the consensus are discussed and highlighted.

OBJECTIVE A new compound, Debrichem (DEBx Medical BV, the Netherlands), a topical desiccation agent (TDA), is an active gel that contains an acidic species with a potent hygroscopic action. When in contact with microorganisms and necrosis, rapid desiccation and carbonisation of the proteins in these microorganisms, as well as of the extracellular matrix of biofilms and necrosis, occurs. The resulting 'precipitate' rapidly dislodges from the wound bed, resulting in a clean wound which granulates, which is a prerequisite for healing by secondary intention. METHOD In a retrospective study, a series of mostly large and hard-to-heal lesions of different aetiologies were treated with a one-time application of the TDA, followed by weekly dressing changes. RESULTS Of the total of 54 lesions included in this case series, 22 were diagnosed as venous leg ulcers (VLUs), 20 as diabetic foot ulcers (DFUs), nine as post-traumatic, hard-to-heal lesions, two as vascular ulcers and one as an ischaemic ulcer. All of the VLUs, 75% of the DFUs and all of the other lesions reached complete granulation. CONCLUSION The use of a TDA may contribute to the consistent, fast and easy removal of both biofilms and necrosis, and hence to wound healing.

Multidrug resistance (MDR) has significantly increased in the past decades and the use of nanotechnology has opened new venues for novel treatments. Nanosulfur is a potent antimicrobial agent and a cheaper alternative to other nanomaterials. However, very few studies have been published on its activity against MDR organisms. Therefore, the goal of this in vitro study was to assess cytotoxicity, antimicrobial, and anti-biofilm activity of nanosulfur (47 nm, orthorhombic) against clinical isolates of MDR Staphylococcus pseudintermedius (SP) and Pseudomonas aeruginosa (PA) in planktonic and biofilm state using canine skin explants. Nanosilver (50 nm, spherical) was tested as a comparative control. Concentrations between 1866.7 and 0.11 μg/mL of both nanoparticles were tested. The ultrastructure of nanosulfur was assessed via electron microscopy. Both types of nanoparticles showed no direct cytotoxicity on a canine keratinocyte cell line. In the planktonic phase, nanosulfur was able to inhibit or kill (6-log10 reduction of CFU) 7 of 10 MDR-SP isolates at 233.3 μg/mL, whereas, when in biofilm state, 6 of 10 isolates were killed at different concentrations (233.33 to 1866.7 μg/mL). Nanosilver did not show any antimicrobial or anti-biofilm activity at any concentrations tested. Both types of nanoparticles were ineffective against MDR-PA in either state. Ultrastructurally, nanosulfur was present in individual nanoparticles as well as forming larger nanoclusters. This is the first study showing an antimicrobial and anti-biofilm activity of nanosulfur for MDR-SP in absence of cytotoxicity. Nanosulfur has the potential to be used in veterinary and human medicine as effective, safe, and cheap alternative to antimicrobials and anti-biofilm agents currently available. • Nanosulfur is a better alternative than nanosilver to treat MDR-Staphylococci. • Nanosulfur is an effective agent against MDR-Staphyloccocal biofilm. • Canine skin explant model is reliable for testing anti-biofilm agents.