Skin Pigmentation Impacts the Clinical Diagnosis of Wound Infection: Imaging of Bacterial Burden to Overcome Diagnostic Limitations.

Underrepresentation of diverse skin tones in medical education and providers' implicit racial bias drives inequities in wound care, such as disproportionally poor outcomes for Black patients. Diagnostic indicators (e.g., erythema) can present differently depending on skin pigmentation. This post hoc analysis of 350 chronic wounds from a prospective 14-site clinical trial aimed to determine how the perception of clinical signs and symptoms of infection (CSS) differs by patient skin tone and if fluorescence-imaging can offer a more objective diagnostic solution. Participants were grouped by skin tone (low, medium, high) as measured by the Fitzpatrick Skin Phototype Classification (FSPC) scale. CSS and total bacterial load (TBL) were compared across FSPC groups, along with sensitivity to detect TBL >104 CFU/g using CSS alone and combined with fluorescence-imaging. Erythema was reported less often with increasing FSPC score (p = 0.05), from 13.4% (low), to 7.2% (medium), to 2.3% (high), despite comparable bacterial loads (median = 1.8 × 106 CFU/g). CSS sensitivity in the high group (2.9%) was 4.8-fold to 8.4-fold lower than the low (p = 0.003) and medium groups (p = 0.04). Fluorescence-imaging significantly improved the detection of high bacterial load in each group, peaking in the high group at 12-fold over CSS alone. These findings underscore the threat of pervasive racialized health inequities in wound care, where missed diagnosis of pathogenic bacteria and infection could delay treatment, increasing the risk of complications and poor outcomes. Fluorescence-imaging is poised to fill this gap, at least in part, serving as a more objective and equitable indicator of wound bacteria. Clinicaltrials.gov #NCT03540004 registered 16-05-2018.

Targeted metagenomic assessment reflects critical colonization in battlefield injuries.

IMPORTANCE: Microbial contamination in combat wounds can lead to opportunistic infections and adverse outcomes. However, current microbiological detection has a limited ability to capture microbial functional genes. This work describes the application of targeted metagenomic sequencing to profile wound bioburden and capture relevant wound-associated signatures for clinical utility. Ultimately, the ability to detect such signatures will help guide clinical decisions regarding wound care and management and aid in the prediction of wound outcomes.

Biocompatibility and Safety Assessment of Combined Topical Ozone and Antibiotics for Treatment of Infected Wounds.

Wound infections with antibiotic-resistant bacteria, particularly the Gram-negative strains, pose a substantial health risk for patients with limited treatment options. Recently topical administration of gaseous ozone and its combination with antibiotics through portable systems has been demonstrated to be a promising approach to eradicate commonly found Gram-negative strains of bacteria in wound infections. However, despite the significant impact of ozone in treating the growing number of antibiotic-resistant infections, uncontrolled and high concentrations of ozone can cause damage to the surrounding tissue. Hence, before such treatments could advance into clinical usage, it is paramount to identify appropriate levels of topical ozone that are effective in treating bacterial infections and safe for use in topical administration. To address this concern, we have conducted a series of in vivo studies to evaluate the efficacy and safety of a portable and wearable adjunct ozone and antibiotic wound therapy system. The concurrent ozone and antibiotics are applied through a wound interfaced gas permeable dressing coated with water-soluble nanofibers containing vancomycin and linezolid (traditionally used to treat Gram-positive infections) and connected to a portable ozone delivery system. The bactericidal properties of the combination therapy were evaluated on an ex vivo wound model infected with Pseudomonas aeruginosa, a common Gram-negative strain of bacteria found in many skin infections with high resistance to a wide range of currently available antibiotics. The results indicated that the optimized combination delivery of ozone (4 mg h-1) and topical antibiotic (200 µg cm-2) provided complete bacteria eradication after 6 h of treatment while having minimum cytotoxicity to human fibroblast cells. Furthermore, in vivo local and systemic toxicity studies (e.g., skin monitoring, skin histopathology, and blood analysis) on pig models showed no signs of adverse effects of ozone and antibiotic combination therapy even after 5 days of continuous administration. The confirmed efficacy and biosafety profile of the adjunct ozone and antibiotic therapy places it as a strong candidate for treating wound infection with antimicrobial-resistant bacteria and further pursuing human clinical trials.

Development of In Vitro and Ex Vivo Biofilm Models for the Assessment of Antibacterial Fibrous Electrospun Wound Dressings.

Increasing evidence suggests that the chronicity of wounds is associated with the presence of bacterial biofilms. Therefore, novel wound care products are being developed, which can inhibit biofilm formation and/or treat already formed biofilms. A lack of standardized assays for the analysis of such novel antibacterial drug delivery systems enhances the need for appropriate tools and models for their characterization. Herein, we demonstrate that optimized and biorelevant in vitro and ex vivo wound infection and biofilm models offer a convenient approach for the testing of novel antibacterial wound dressings for their antibacterial and antibiofilm properties, allowing one to obtain qualitative and quantitative results. The in vitro model was developed using an electrospun (ES) thermally crosslinked gelatin-glucose (GEL-Glu) matrix and an ex vivo wound infection model using pig ear skin. Wound pathogens were used for colonization and biofilm development on the GEL-Glu matrix or pig skin with superficial burn wounds. The in vitro model allowed us to obtain more reproducible results compared with the ex vivo model, whereas the ex vivo model had the advantage that several pathogens preferred to form a biofilm on pig skin compared with the GEL-Glu matrix. The in vitro model functioned poorly for Staphylococcus epidermidis biofilm formation, but it worked well for Escherichia coli and Staphylococcus aureus, which were able to use the GEL-Glu matrix as a nutrient source and not only as a surface for biofilm growth. On the other hand, all tested pathogens were equally able to produce a biofilm on the surface of pig skin. The developed biofilm models enabled us to compare different ES dressings [pristine and chloramphenicol-loaded polycaprolactone (PCL) and PCL-poly(ethylene oxide) (PEO) (PCL/PEO) dressings] and understand their biofilm inhibition and treatment properties on various pathogens. Furthermore, we show that biofilms were formed on the wound surface as well as on a wound dressing, indicating that the demonstrated methods mimic well the in vivo situation. Colony forming unit (CFU) counting and live biofilm matrix as well as bacterial DNA staining together with microscopic imaging were performed for biofilm quantification and visualization, respectively. The results showed that both wound biofilm models (in vitro and ex vivo) enabled the evaluation of the desired antibiofilm properties, thus facilitating the design and development of more effective wound care products and screening of various formulations and active substances.

Human Wound and Its Burden: Updated 2020 Compendium of Estimates.

Significance: Chronic wounds impact the quality of life (QoL) of nearly 2.5% of the total population in the United States and the management of wounds has a significant economic impact on health care. Given the aging population, the continued threat of diabetes and obesity worldwide, and the persistent problem of infection, it is expected that chronic wounds will continue to be a substantial clinical, social, and economic challenge. In 2020, the coronavirus disease (COVID) pandemic dramatically disrupted health care worldwide, including wound care. A chronic nonhealing wound (CNHW) is typically correlated with comorbidities such as diabetes, vascular deficits, hypertension, and chronic kidney disease. These risk factors make persons with CNHW at high risk for severe, sometimes lethal outcomes if infected with severe acute respiratory syndrome coronavirus 2 (pathogen causing COVID-19). The COVID-19 pandemic has impacted several aspects of the wound care continuum, including compliance with wound care visits, prompting alternative approaches (use of telemedicine and creation of videos to help with wound dressing changes among others), and encouraging a do-it-yourself wound dressing protocol and use of homemade remedies/substitutions. Recent Advances: There is a developing interest in understanding how the social determinants of health impact the QoL and outcomes of wound care patients. Furthermore, addressing wound care in the light of the COVID-19 pandemic has highlighted the importance of telemedicine options in the continuum of care. Future Directions: The economic, clinical, and social impact of wounds continues to rise and requires appropriate investment and a structured approach to wound care, education, and related research.

In-Vitro Assessment Of The Therapeutic Potential Of Polymyxins And Tigecycline Against Multidrugresistant Acinetobacter Isolates From Infected Wounds.

BACKGROUND: The incidence of multidrug-resistant (MDR), extreme drug resistant (XDR), and pan drug-resistant (PDR) Acinetobacter are increasing throughout the world. The therapeutic management and control of Acinetobacter are difficult due to the emergence of drug resistance and its enduring capacity to survive in the environment. The present study was designed to appraise the efficacy of Polymyxins and Tigecycline against multidrugresistant Acinetobacter isolates from surgical and burn wounds. METHODS: During the study, the specimens were collected from various types of wounds from inpatients and outpatients of the tertiary care hospitals of Lahore, Pakistan in 2017 and 2018. The bacterial pathogens were isolated and identified using standard microbiological procedures and molecular confirmation of Acinetobacter species was examined by PCR using specific primers. The antibiotic susceptibility profiling of Acinetobacter isolates was studied against 18 antibiotics as per Clinical and Laboratory Standards Institute (CLSI) guidelines. RESULTS: The Acinetobacter isolates demonstrated extreme resistance especially to ampicillin/sulbactam, piperacillin/tazobactam, cephalosporins, carbapenems, fluoroquinolones, and aminoglycosides. However, the colistin, polymyxin, and tigecycline remained the most effective antimicrobial agents against Acinetobacter isolates. CONCLUSIONS: The results highlight the extent of drug resistance and therapeutic potential of Polymyxins and Tigecycline for wound infections caused by MDR and XDR Acinetobacter species. The wiser use of antimicrobials, incessant surveillance of antimicrobial resistance, and stringent adherence to infection control guidelines are critical to reducing major outbreaks in the future.

Green synthesis of silver nanoparticles using Carum copticum: Assessment of its quorum sensing and biofilm inhibitory potential against gram negative bacterial pathogens.

Antimicrobial resistance among pathogenic bacteria has become a global threat to human health. Due to poor progress in development of new antimicrobial drugs, there is a need for the development of novel alternative strategies to combat the problem of multidrug resistance. Moreover, there is focus on ecofriendly approach for the synthesis nanoparticles having efficient medicinal properties including antivirulence properties to tackle the emergence of multi-drug resistance. Targeting quorum sensing controlled virulence factors and biofilms has come out to be a novel anti-infective drug target. The silver nanoparticles (Ag@CC-NPs) were synthesized from aqueous extract of Carum copticum and characterized using UV-vis absorption spectroscopy, fourier-transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Ag@CC-NPs were checked for its ability to inhibit quorum sensing-mediated virulence factors and biofilms against three test pathogens at sub-MIC values. There was ~75% inhibition of violacein production by Ag@CC-NPs against C. violaceum. The P. aeruginosa virulence factors such as pyocyanin production, pyoverdin production, exoprotease activity, elastase activity, swimming motility and rhamnolipid production were inhibited by 76.9, 49.0, 71.1, 53.3, 89.5, and 60.0% at sub-MIC. Moreover, virulence factors of S. marcescens viz. prodigiosin production, exoprotease activity, and swarming motility was reduced by 78.4, 67.8, and 90.7%. Ag@CC-NPs also exhibited broad-spectrum antibiofilm activity with 77.6, 86.3, and 75.1% inhibition of biofilms of P. aeruginosa, S. marcescens, and C. violaceum respectively. The biofilm formation on glass coverslip was reduced remarkably as evident from SEM and CLSM analysis. The findings revealed the in vitro efficacy of Ag@CC-NPs against bacterial pathogens and can be exploited in the development of alternative therapeutic agent in management of bacterial infections for topical application, mainly wound infection, or coating of surfaces to prevent bacterial adherence on medical devices.

Assessment of the Efficacy of Tributylammonium Alginate Surface-Modified Polyurethane as an Antibacterial Elastomeric Wound Dressing for both Noninfected and Infected Full-Thickness Wounds.

Risk factors of nonhealing wounds include persistent bacterial infections and rapid onset of dehydration; therefore, wound dressings should be used to accelerate the healing process by helping to disinfect the wound bed and provide moisture. Herein, we introduce a transparent tributylammonium alginate surface-modified cationic polyurethane (CPU) wound dressing, which is appropriate for full-thickness wounds. We studied the physicochemical properties of the dressing using Fourier transform infrared, 1H NMR, and 13C NMR spectroscopies and scanning electron microscopy, energy-dispersive X-ray, and thermomechanical analyses. The surface-modified polyurethane demonstrated improved hydrophilicity and tensile Young's modulus that approximated natural skin, which was in the range of 1.5-3 MPa. Cell viability and in vitro wound closure, assessed by MTS and the scratch assay, confirmed that the dressing was cytocompatible and possessed fibroblast migratory-promoting activity. The surface-modified CPU had up to 100% antibacterial activity against Staphylococcus aureus and Escherichia coli as Gram-positive and Gram-negative bacteria, respectively. In vivo assessments of both noninfected and infected wounds revealed that the surface-modified CPU dressing resulted in a faster healing rate because it reduced the persistent inflammatory phase, enhanced collagen deposition, and improved the formation of mature blood vessels when compared with CPU and commercial Tegaderm wound dressing.

Benefits of Acidifying Agents in Local Therapy of Diabetic Foot Ulcers Infected by Pseudomonas sp: A Pilot Study.

Infections caused by Pseudomonas sp are difficult to resolve by antibiotics (ATBs) and local therapy. The aim of our pilot study was to assess the effect of different local agents-particularly acidifying solutions-on the healing of diabetic foot ulcers (DFUs), eradication of pathogens, and economic costs related to DFU therapy. In this case study, we monitored 32 DFU patients infected by Pseudomonas species. Patients were divided into 2 groups according to the local therapy provided: group 1 (n = 15)-modern local treatment; group 2 (n = 17)-acidifying antiseptic solutions. The study groups differed only with regard to ATB usage prior to enrolment in the study (P = .004), but did not differ with regard to age, diabetes control, peripheral arterial disease, or microcirculation status. During the follow-up period, DFUs healed in 20% of cases in group 1, but there were no cases of healing in group 2 (NS). The length of ATB therapy, the number of new osteomyelitis, lower limb amputations, and the changes of DFUs status/proportions did not differ significantly between study groups. Pseudomonas was eradicated in 67% of cases in group 1 and in 65% of cases in group 2. The local treatment given to group 2 patients was associated with lower costs (P < .0001). Conclusion. Acidifying agents had the same effect as modern healing agents on wound healing, the number of amputations, and the eradication of Pseudomonas. Moreover, therapy performed using acidifying solutions proved in our pilot study markedly cheaper.

Efficacy and safety assessment of two enterococci phages in an in vitro biofilm wound model.

Chronic wounds affect thousands of people worldwide, causing pain and discomfort to patients and represent significant economical burdens to health care systems. The treatment of chronic wounds is very difficult and complex, particularly when wounds are colonized by bacterial biofilms which are highly tolerant to antibiotics. Enterococcus faecium and Enterococcus faecalis are within the most frequent bacteria present in chronic wounds. Bacteriophages (phages) have been proposed as an efficient and alternative against antibiotic-resistant infections, as those found in chronic wounds. We have isolated and characterized two novel enterococci phages, the siphovirus vB_EfaS-Zip (Zip) and the podovirus vB_EfaP-Max (Max) to be applied during wound treatment. Both phages demonstrated lytic behavior against E. faecalis and E. faecium. Genome analysis of both phages suggests the absence of genes associated with lysogeny. A phage cocktail containing both phages was tested against biofilms formed in wound simulated conditions at a multiplicity of infection of 1.0 and a 2.5 log CFU.mL-1 reduction in the bacterial load after at 3 h of treatment was observed. Phages were also tested in epithelial cells colonized by these bacterial species and a 3 log CFU.mL-1 reduction was observed using both phages. The high efficacy of these new isolated phages against multi-species biofilms, their stability at different temperatures and pH ranges, short latent periods and non-cytotoxicity to epithelial cells suggest their therapeutic use to control infectious biofilms present in chronic wounds.

An in vitro assessment of bacterial transfer by products used in debridement.

OBJECTIVE: The aim of this in vitro study was to investigate the transfer of viable Pseudomonas aeruginosa biofilm microorganisms following treatment with debridement tools. METHOD: The level of viable biofilm microorganisms transferred by debridement tools was compared following treatment that reflected the clinical practice of each product. RESULTS: A significant level of microorganism transfer was seen in response to the mechanical debridement tool. Minimal transfer of microorganisms was seen when in vitro-established biofilms were treated with hydroresponsive wound dressing + polyhexamethylene biguanide (HRWD+PHMB, HydroClean plus). Less Pseudomonas aeruginosa was recovered from explants exposed to dressings compared with those exposed to debridement tools suggesting that there was less transfer of bacteria by dressings. CONCLUSION: The reduced transfer of viable microorganisms by HRWD+PHMB may be the result of significant binding and retention of microbes by the superabsorbent polymer within the dressing, together with enhanced sequestered bacterial killing within the dressing by polymer-bound PHMB. The high levels of microbial transfer/transmission seen for debridement tools suggests that, in the clinical setting, a significant level of bacterial spread over the wound surface and/or surrounding skin by these cleansing tools is likely.

Clinical Assessment of a Biofilm-disrupting Agent for the Management of Chronic Wounds Compared With Standard of Care: A Therapeutic Approach.

OBJECTIVE: The authors study the use of a biofilm-disrupting wound gel designed for wound management to determine if disrupting chronic wound biofilm would be therapeutically efficacious. MATERIALS AND METHODS: This prospective, randomized, open-label clinical trial was performed from September 2014 through March 2016. Forty-three patients (22 experimental, 21 control) with chronic, recalcitrant wounds were randomized to a 12-week treatment with a biofilm-disrupting wound gel (experimental) or a broad-spectrum antimicrobial ointment (control). The wound healing rate was assessed by measuring wound size reduction and wound closure rates. RESULTS: Wound size in the experimental group decreased significantly with a 71% reduction in wound area compared with 24% for the control (P < .001). Wound closure was attained in more than half of the patients (14) treated with the experimental product. Fifty-three percent of these patients achieved closure by 12 weeks as opposed to 17% for the control (P < .01). No adverse events related to the experimental product were recorded, but 2 adverse reactions occurred with the control. CONCLUSIONS: The combination of the experimental product and wound debridement significantly improved wound healing rates by disrupting the biofilm, which protects multispecies bacteria within a chronic wound. Given the significant wound size reduction and closure rates observed in these long-term, nonhealing wounds, as well as the lack of related serious adverse events, the investigators believe the biofilm-disrupting wound gel to be a safe and effective treatment for recalcitrant chronic wounds.

A 2000 patient retrospective assessment of a new strategy for burn wound management in view of infection prevention and treatment.

Infections in burn patients are still the principal cause of complications in burn injuries. The aim of this study is to assess a new strategy for burn wound management in view of infection prevention and treatment in the experience of the Burn Treatment Center in Siemianowice Slaskie. The applied methodology involved the analysis of patient records describing the hospital's epidemiological situation between 2014 and 2016. The analysis also included the use and cost of antibiotics, silver-containing dressings, and other antiseptics relative to the number of sepsis cases, including those caused by Pseudomonas aeruginosa, as well as the mortality ratio. The total costs of prevention and treatment of infections were reduced, while the use of silver-containing dressings and antiseptics increased. The number of patients with sepsis decreased, including cases caused by P. aeruginosa, and the mortality ratio was reduced. Introducing a strategy for burn wound-oriented infection prevention and treatment in burn patients provides a number of benefits. It is also cost-effective. Using locally applied active dressings and antiseptics can be a welcome choice for often-unnecessary antibiotic therapy of a suspected or existing burn wound infection.

A Clinicoepidemiological Profile of Chronic Wounds in Wound Healing Department in Shanghai.

The aim of the study was to update the clinical database of chronic wounds in order to derive an evidence based understanding of the condition and hence to guide future clinical management in China. A total of 241 patients from January 1, 2011 to April 30, 2016 with chronic wounds of more than 2 weeks' duration were studied in wound healing department in Shanghai. Results revealed that among all the patients the mean age was 52.5 ± 20.2 years (range 2-92 years). The mean initial area of wounds was 30.3 ± 63.0 cm2 (range 0.25-468 cm2). The mean duration of wounds was 68.5 ± 175.2 months (range 0.5-840 months). The previously reported causes of chronic wounds were traumatic or surgical wounds (n = 82, 34.0%), followed by pressure ulcers (n = 59, 24.5%). To study the effects of age, patients were divided into 2 groups: less than 60 years (<60), and 60 years or older (≥60). The proportion of wounds etiology between the 2 age groups was analyzed, and there was significant statistical difference ( P < .05, 95% confidence interval [CI] = 0.076-0.987). To study the associations between outcome and clinical characteristics in chronic wounds, chi-square test was used. There were significant differences in the factor of wound infection. ( P = .035, 95% CI = 0.031-0.038) Regarding therapies, 72.6% (n = 175) of the patients were treated with negative pressure wound therapy. Among all the patients, 29.9% (n = 72) of them were completely healed when discharged while 62.7% (n = 150) of them improved. The mean treatment cost was 12055.4 ± 9206.3 Chinese Yuan (range 891-63626 Chinese Yuan). In conclusion, traumatic or surgical wounds have recently become the leading cause of chronic wounds in Shanghai, China. Etiology of the 2 age groups was different. Infection could significantly influence the wound outcome.

Case Report: Diabetic Foot Ulcer Infection Treated with Topical Compounded Medications.

An adult diabetic male with three toes amputated on his right foot presented with an ulcer infection on his left foot, unresponsive to conventional antifungal oral medication for over two months. The ulcerated foot wound had a large impairment on the patient's quality of life, as determined by the Wound-QoL questionnaire. The compounding pharmacist recommended and the physician prescribed two topical compounded medicines, which were applied twice a day, free of charge at the compounding pharmacy. The foot ulcer infection was completely resolved following 13 days of treatment, with no longer any impairment on the patient's quality of life. This scientific case study highlights the value of pharmaceutical compounding in current therapeutics, the importance of the triad relationship, and the key role of the compounding pharmacist in diabetes care.

Highly sensitive label-free dual sensor array for rapid detection of wound bacteria.

Wound infections are a critical healthcare concern worldwide. Rapid and effective antibiotic treatments that can mitigate infection severity and prevent the spread of antibiotic resistance are contingent upon timely infection detection. In this work, dual electrochemical pH and cell-attachment sensor arrays were developed for the real-time spatial and temporal monitoring of potential wound infections. Biocompatible polymeric device coatings were integrated to stabilize the sensors and promote bacteria attachment while preventing non-specific cell and protein fouling. High sensitivity (bacteria concentration of 102 colony forming units (CFU)/mL and -88.1±6.3mV/pH over a pH range of 1-13) and stability over 14 days were achieved without the addition of biological recognition elements. The dual sensor array was demonstrated to successfully monitor the growth of both gram-positive (Staphylococcus aureus and Streptococcus pyogenes) and gram-negative bacteria (Pseudomonas aeruginosa and Escherichia coli) over time through lag and log growth phases and following antibiotic administration and in simulated shallow wounds conditions. The versatile fabrication methods utilized in sensor development, superior sensitivity, prolonged stability, and lack of non-specific sensor fouling may enable long-term in situ sensor array operation in low resource settings.

Clinical effectiveness, quality of life and cost-effectiveness of Flaminal® versus Flamazine® in the treatment of partial thickness burns: study protocol for a randomized controlled trial.

BACKGROUND: Partial thickness burns are painful, difficult to manage and can have a negative effect on quality of life through scarring, permanent disfigurement and loss of function. The aim of burn treatment in partial thickness burns is to save lives, stimulate wound healing by creating an optimumly moist wound environment, to have debriding and analgesic effects, protect the wound from infection and be convenient for the patient and caregivers. However, there is no consensus on the optimal treatment of partial thickness wounds. Flaminal® and Flamazine® are two standard treatment options that provide the above mentioned properties in burn treatment. Nevertheless, no randomized controlled study has yet compared these two common treatment modalities in partial thickness burns. Thus, the aim of this study is to evaluate the clinical effectiveness, quality of life and cost-effectiveness of Flaminal® versus Flamazine® in the treatment of partial thickness burns. METHODS/DESIGN: In this two-arm open multi-center randomized controlled trial, 90 patients will be randomized between Flaminal® and Flamazine® and followed for 12 months. The study population will consist of competent or temporarily non-competent (because of sedation and/or intubation) patients, 18 years of age or older, with acute partial thickness burns and a total body surface area (TBSA) of less than 30 %. The main study outcome is time to complete re-epithelialization (greater than 95 %). Secondary outcome measures include need for grafting, wound colonization/infection, number of dressing changes, pain and anxiety, scar formation, health-related quality of life (HRQoL), and costs. DISCUSSION: This study will contribute to the optimal treatment of patients with partial thickness burn wounds and will provide evidence on the (cost-)effectiveness and quality of life of Flaminal® versus Flamazine® in the treatment of partial thickness burns. TRIAL REGISTRATION: Netherlands Trial Register NTR4486 , registered on 2 April 2014.

Burden of Infected Diabetic Foot Ulcers on Hospital Admissions and Costs.

BACKGROUND: Costs related to diabetic foot ulcer (DFU) care are greater than $1 billion annually and rising. We sought to describe the impact of diabetes mellitus (DM) on foot ulcer admissions in the United States, and to investigate potential explanations for rising hospital costs. METHODS: The Nationwide Inpatient Sample (2005-2010) was queried using International Classification of Diseases, 9th Revision (ICD-9) codes for a primary diagnosis of foot ulceration. Multivariable analyses were used to compare outcomes and per-admission costs among patients with foot ulceration and DM versus non-DM. RESULTS: In total, 962,496 foot ulcer patients were admitted over the study period. The overall rate of admissions was relatively stable over time, but the ratio of DM versus non-DM admissions increased significantly (2005: 10.2 vs. 2010: 12.7; P < 0.001). Neuropathy and infection accounted for 90% of DFU admissions, while peripheral vascular disease accounted for most non-DM admissions. Admissions related to infection rose significantly among DM patients (2005: 39,682 vs. 2010: 51,660; P < 0.001), but remained stable among non-DM patients. Overall, DM accounted for 83% and 96% of all major and minor amputations related to foot ulcers, respectively, and significantly increased cost of care (DM: $1.38 vs. non-DM: $0.13 billion/year; P < 0.001). Hospital costs per DFU admission were significantly higher for patients with infection compared with all other causes ($11,290 vs. $8,145; P < 0.001). CONCLUSIONS: Diabetes increases the incidence of foot ulcer admissions by 11-fold, accounting for more than 80% of all amputations and increasing hospital costs more than 10-fold over the 5 years. The majority of these costs are related to the treatment of infected foot ulcers. Education initiatives and early prevention strategies through outpatient multidisciplinary care targeted at high-risk populations are essential to preventing further increases in what is already a substantial economic burden.

Extracellular matrix assessment of infected chronic venous leg ulcers: role of metalloproteinases and inflammatory cytokines.

Chronic venous ulcer (CVU) represents a dreaded complication of chronic venous disease (CVD). The onset of infection may further delay the already precarious healing process in such lesions. Some evidences have shown that matrix metalloproteinases (MMPs) are involved and play a central role in both CVUs and infectious diseases. Two groups of patients were enrolled to evaluate the expression of MMPs in infected ulcers and the levels of inflammatory cytokines as well as their prevalence. Group I comprised 63 patients (36 females and 27 males with a median age of 68·7 years) with infected CVUs, and group II (control group) comprised 66 patients (38 females and 28 males with a median age of 61·2 years) with non-infected venous ulcers. MMP evaluation and dosage of inflammatory cytokines in plasma and wound fluid was performed by means of enzyme-linked immunosorbent assay test; protein extraction and immunoblot analysis were performed on biopsied wounds. The first three most common agents involved in CVUs were Staphylococcus aureus (38·09%), Corynebacterium striatum (19·05%) and Pseudomonas aeruginosa (12·7%). In this study, we documented overall higher levels of MMP-1 and MMP-8 in patients with infected ulcers compared to those with uninfected ulcers that showed higher levels of MMP-2 and MMP-9. We also documented higher levels of interleukin (IL)-1, IL-6, IL-8, vascular endothelial growth factor and tumour necrosis factor-alpha in patients with infected ulcers with respect to those with uninfected ulcers, documenting a possible association between infection, MMP activation, cytokine secretions and symptoms. The present results could represent the basis for further studies on drug use that mimic the action of tissue inhibitors of metalloproteinases in order to make infected CVU more manageable.