Infected Diabetic Foot Ulcers Research Articles

Genetic Characterization of Methicillin-Resistant Staphylococcus aureus Isolated From Diabetic Foot Ulcers in a Tertiary Care Hospital in Mysuru, South India.

Background Diabetic foot ulcers (DFUs) are common complications in diabetes patients, often leading to sepsis and leg amputation. Methicillin-resistant Staphylococcus aureus (MRSA) infections in DFUs pose challenges due to methicillin resistance with mecA and mecC genes. This study aims to assess the prevalence of MRSA in clinical isolates from DFUs,analyze the antibiogram of MRSA isolates, and detect the presence of the mecA and mecC genes among MRSA isolates. Methodology The isolated S. aureus colonies were identified and antimicrobial susceptibility was performed using the Vitek-2 Compact system. Methicillin resistance was also confirmed through the disc diffusion method. Confirmed methicillin-resistant isolates were subjected to real-time polymerase chain reaction (RT-PCR) to detect mecA and mecC genes. Results A total of 474 purulent samples from DFUs yielded 541 distinct isolates, comprising 201 gram-positive and 340 gram-negative organisms. Among the gram-positive organisms, Staphylococcus species predominated, with 79 S. aureus isolates, 34 of which were methicillin-resistant. All MRSA isolates (100%) were sensitive to tetracycline, linezolid, teicoplanin, and vancomycin, and 94% were sensitive to cotrimoxazole but least susceptible to ciprofloxacin and levofloxacin. RT-PCR confirmed the presence of mecA genes in all 34 isolates and mecC genes in three isolates. Conclusions The presence of mecA in all 34 MRSA isolates underscores consistent methicillin resistance. The co-occurrence of mecA and mecC in three isolates hints at genetic diversity. Two MRSA isolates positive for mecC were isolated from rural patients involved in farming and animal husbandry, suggesting an occupational risk. The third patient was from a non-rural area, indicating potential alternative transmission pathways warranting further investigation.

Systematic review and meta-analysis of the diagnostic accuracy of inflammatory markers for infected diabetic foot ulcer

The aim was to evaluate the diagnostic value of ESR, CPR, PCT, and WBC in patients with infected diabetic foot ulcer (DFU). The MEDLINE, Embase, BIOSIS, Cochrane databases, and Web of Knowledge databases were searched, without language restriction, to July 2023. Original studies were selected that reported the performance of ESR, CPR, PCT, and WBC in diagnosing infected DFU. To assess the diagnostic value of biomarkers for infected DFU, pooled sensitivity, specificity, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratio (DOR), and area under the summary receiver operating characteristic curve (ROC-AUC) were calculated. Ten studies with 765 patients were identified in our meta-analysis. The pooled sensitivity and specificity of ESR was 0.82 (95% CI: 0.68-0.91) and 0.83 (95% CI: 0.69-0.91) respectively. The pooled sensitivity and specificity of CRP was 0.81 (95% CI: 0.65-0.91) and 0.91 (95% CI: 0.79-0.96) respectively. The pooled sensitivity and specificity of PCT was 0.76 (95% CI: 0.65-0.85) and 0.89 (95% CI: 0.78-0.95) respectively. The pooled sensitivity and specificity of WBC was 0.75 (95% CI: 0.64-0.83) and 0.79 (95% CI: 0.67-0.88) respectively. CRP showed the best diagnostic accuracy at distinguishing infected DFU from noninfected DFU with an AUC of 0.93, followed by PCT (AUC of 0.89), ESR (AUC of 0.89), and WBC (AUC of 0.84). CPR levels had high efficiency in distinguishing infected DFU from noninfected DFU, followed by PCT, ESR and WBC. All of these biomarkers could be helpful for early diagnosis of infected DFU. New biomarkers for improving medical decision in diagnosis of infected DFU are highly desirable.

Inflammatory Markers Influencing Mortality Rates in Diabetic Foot Ulcer – A Prospective Study

This study aimed to explore the relationship between inflammatory markers, apolipoprotein E (ApoE) levels, renal function, and mortality in patients with diabetic foot ulcers (DFUs). Conducted as a single-center prospective study at the Clinical County Emergency Hospital of Arad, Romania, the study included 90 patients diagnosed with infected DFUs. The main objective was to determine the risk factors for mortality over a three-year follow-up period, focusing on early versus late deaths. The results indicated a significant correlation between elevated levels of ApoE, pentraxin 3 (PTX3), procalcitonin (PCT), and impaired renal function with increased mortality. Patients with higher levels of these biomarkers, particularly those with impaired renal function, were more likely to experience early death, especially within the first 90 days after surgery. The findings underscore the critical role of these factors in predicting mortality and highlight the need for early intervention and aggressive management of these risk factors to improve outcomes in this vulnerable population. Despite advancements in medical and surgical care, the prognosis for patients with DFUs remains poor, particularly due to the recurrent nature of the ulcers and the presence of comorbidities like chronic kidney disease.

SwinDFU-Net: Deep learning transformer network for infection identification in diabetic foot ulcer.

The identification of infection in diabetic foot ulcers (DFUs) is challenging due to variability within classes, visual similarity between classes, reduced contrast with healthy skin, and presence of artifacts. Existing studies focus on visual characteristics and tissue classification rather than infection detection, critical for assessing DFUs and predicting amputation risk. To address these challenges, this study proposes a deep learning model using a hybrid CNN and Swin Transformer architecture for infection classification in DFU images. The aim is to leverage end-to-end mapping without prior knowledge, integrating local and global feature extraction to improve detection accuracy. The proposed model utilizes a hybrid CNN and Swin Transformer architecture. It employs the Grad CAM technique to visualize the decision-making process of the CNN and Transformer blocks. The DFUC Challenge dataset is used for training and evaluation, emphasizing the model's ability to accurately classify DFU images into infected and non-infected categories. The model achieves high performance metrics: sensitivity (95.98%), specificity (97.08%), accuracy (96.52%), and Matthews Correlation Coefficient (0.93). These results indicate the model's effectiveness in quickly diagnosing DFU infections, highlighting its potential as a valuable tool for medical professionals. The hybrid CNN and Swin Transformer architecture effectively combines strengths from both models, enabling accurate classification of DFU images as infected or non-infected, even in complex scenarios. The use of Grad CAM provides insights into the model's decision process, aiding in identifying infected regions within DFU images. This approach shows promise for enhancing clinical assessment and management of DFU infections.

Targeting Matrix Metalloproteinase-9 for Therapeutic Intervention in Diabetic Foot Ulcers.

Diabetic foot ulcers (DFUs) are a complication of diabetes that have long been neglected. To date, a single drug (becaplermin containing platelet-derived growth factor, PDGF) has been approved by the FDA 27 years ago; however, it is seldom used because of its modest efficacy. The standard-of-care for DFUs is debridement, off-loading, and infection control with antibiotics, with hyperbaric oxygen (HBO) therapy being the treatment of last recourse. The paucity of understanding what accelerates diabetic wound healing results in more than 150,000 lower-limb amputations in the United States every year. A new paradigm for treatment of DFUs is proposed based on the higher levels of active matrix metalloproteinase (MMP)-9 with the more severe and infected human DFUs, and the demonstrated detrimental role of MMP-9 and the beneficial repair role of MMP-8 in diabetic mice. Selective inhibition of MMP-9 with the small molecule (R)-ND-336 lowered inflammation, reduced reactive oxygen species (ROS), and increased angiogenesis, without affecting MMP-8 to allow the natural repair mechanisms to take place. (R)-ND-336 showed better efficacy than becaplermin in diabetic mice. Becaplermin (PDGF) and HBO therapy work by decreasing MMP-9, but they do not completely suppress MMP-9 activity.

Automated Detection of Infection in Diabetic Foot Ulcer Using Pre-trained Fast Convolutional Neural Network with U++net

Automated Detection of Infection in Diabetic Foot Ulcer Using Pre-trained Fast Convolutional Neural Network with U++net

Integrating Zinc Cream-Chitosan and Cadexomer Iodine for Treating Infections in Diabetic Foot Ulcers: A Case Report

Integrating Zinc Cream-Chitosan and Cadexomer Iodine for Treating Infections in Diabetic Foot Ulcers: A Case Report

The antimicrobial susceptibility patterns of diabetic foot ulcers in the South African public healthcare sector.

Diabetic foot syndrome is defined as the presence of a diabetic foot ulcer (DFU) associated with neuropathy, peripheral artery disease and infection. While the use of antimicrobials in the treatment of DFU infection remains a mainstay, the choice of antimicrobial remains problematic owing to the presence of multidrug-resistant polymicrobial infections. In the South African public healthcare sector, the treatment of DFUs is based on the Standard Treatment Guidelines (STGs) and the Essential Drug List. These guidelines are developed using evidence-based medicine and are based on global susceptibility patterns rather than local susceptibility data, and may not provide the most appropriate treatment options. To determine the antimicrobial susceptibility patterns of DFUs isolated from patients visiting selected Gauteng provincial public hospitals in order to determine a clinically effective treatment protocol for the management of these infections. Sample swabs were taken from 51 DFUs using the Levine method. Each sample swab was spread onto blood agar plates, and thereafter individual pathogens were isolated. The antimicrobial susceptibility patterns of all isolated pathogens were determined using zone of inhibition measurements. Pathogens were grouped according to macromorphological characteristics as well as susceptibility patterns, and a representative isolate from each group was then identified. A total of 51 DFU ulcer swabs from 45 patients were included in the study. From the sample swabs, a total of 445 pathogens were isolated. The most effective antimicrobial was found to be gentamicin, followed by ciprofloxacin. Amoxicillin/clavulanic acid, the first-line treatment according to the STGs, was found to be ineffective for many of the isolated pathogens. The most commonly isolated pathogens were Proteus mirabilis, Enterococcus faecalis and Pseudomonas aeruginosa. These findings demonstrate the urgent need to reassess the STGs and base treatment plans on local epidemiological data. This study provides valuable data on common causative pathogens in DFU infections, as well as the resistance patterns of these pathogens, forming a baseline on which to base future DFU treatment plans.

Limb salvage and systemic management of gouty tophi: Case series.

Gout is a chronic disease characterized by deposition of monosodium urate crystals. Tophi develop in some individuals with untreated or uncontrolled gout, which leads to ulcerations, cosmetic problems, mechanical obstruction of joint movement, joint damage and musculoskeletal disability. Currently, the treatment of gouty tophi is controversial and challenging. Both surgical and internal medical treatments have limitations and require further exploration in clinical practice. In Case 1, we treated a patient with severe infection of diabetic foot ulcers with concomitant multiple gouty tophi in the same limb. A systematic management strategy was formulated to close the wound and save the limb. The ulcers healed successfully after half a year. In Case 2, a giant gouty tophi located in the first metatarsophalangeal joint of the left foot was removed by surgical treatment and vancomycin-loaded bone cement implantation. In Case 3, we present a case of gouty tophi that was resolved by standardized systemic medical management. Three patients were all diagnosed with gout accompanied by gouty deposition, although there were other different comorbidities. In case 1, we used debridement to gradually remove gouty tophi. In case 2, the giant gouty tophi was removed by surgical operation. In case 3, the gouty tophi disappeared after standardized treatment with medicine, diet and lifestyle management. Three patients underwent different treatment therapies to remove gouty tophi based on their specific conditions. We explored effective interventions for tophi in gout by surgical or other interventions in combination with pharmacotherapy.

Definitive single-stage surgery for treating diabetic foot osteomyelitis: a protocolized pathway including antibiotic bone graft substitute use.

Diabetic foot ulcers (DFUs) are a challenging complication of diabetes mellitus, often leading to poor clinical outcomes and significant socioeconomic burdens. We evaluated the effectiveness of a definitive single-stage protocolized surgical management pathway, including the use of local antibiotic bone graft substitute, for the treatment of infected DFUs with associated osteomyelitis. A retrospective cohort study was conducted. Medical records were extracted (from January 2017 to December 2020) to establish a database consisting of patients who underwent surgical intervention for the treatment of an infected DFU with osteomyelitis. Patients were divided into conventional (control) and protocolized (intervention) surgical groups depending on the treatment received. Clinical outcomes were assessed over a 12-month follow-up period. A total of 136 consecutive patients were included (conventional = 33, protocolized = 103). The protocolized group demonstrated a statistically significant reduction in the mean number of operations performed per patient (1.2 vs. 3.5) (P < 0.001) and a shorter accumulative hospital length of stay (12.6 vs. 25.1 days) (P < 0.001) compared to the conventional group. Major amputation rates were significantly lower in the protocolized group (2% vs. 18%) (P < 0.001). Within 12 months of surgical intervention, the protocolized group exhibited an ulcer healing rate of 89%, with a low rate of recurrence (3%). The protocolized surgical pathway, including local antibiotic bone graft substitute use, demonstrated superior outcomes compared to conventional management for the treatment of infected DFUs with osteomyelitis. Further research is needed to evaluate the cost-effectiveness and generalizability of this approach.

Does PAD and microcirculation status impact the tissue availability of intravenously administered antibiotics in patients with infected diabetic foot? Results of the DFIATIM substudy.

The aim of this substudy (Eudra CT No:2019-001997-27)was to assess ATB availability in patients with infected diabetic foot ulcers(IDFUs)in the context of microcirculation and macrocirculation status. For this substudy, we enrolled 23 patients with IDFU. Patients were treated with boluses of amoxicillin/clavulanic acid(AMC)(12patients) or ceftazidime(CTZ)(11patients). After induction of a steady ATB state, microdialysis was performed near the IDFU. Tissue fluid samples from the foot and blood samples from peripheral blood were taken within 6 hours. ATB potential efficacy was assessed by evaluating the maximum serum and tissue ATB concentrations(Cmax and Cmax-tissue)and the percentage of time the unbound drug tissue concentration exceeds the minimum inhibitory concentration (MIC)(≥100% tissue and ≥50%/60% tissue fT>MIC). Vascular status was assessed by triplex ultrasound, ankle-brachial and toe-brachial index tests, occlusive plethysmography comprising two arterial flow phases, and transcutaneous oxygen pressure(TcPO2). Following bolus administration, the Cmax of AMC was 91.8 ± 52.5 μgmL-1 and the Cmax-tissue of AMC was 7.25 ± 4.5 μgmL-1(P<0.001). The Cmax for CTZ was 186.8 ± 44.1 μgmL-1 and the Cmax-tissue of CTZ was 18.6 ± 7.4 μgmL-1(P<0.0001). Additionally, 67% of patients treated with AMC and 55% of those treated with CTZ achieved tissue fT>MIC levels exceeding 50% and 60%, respectively. We observed positive correlations between both Cmax-tissue and AUCtissue and arterial flow. Specifically, the correlation coefficient for the first phase was r=0.42; (P=0.045), and for the second phase, it was r=0.55(P=0.01)and r=0.5(P=0.021). Bactericidal activity proved satisfactory in only half to two-thirds of patients with IDFUs, an outcome that appears to correlate primarily with arterial flow.

Activated carbon cloth versus silver-based dressings in a population with diabetic foot ulcer: a randomised controlled trial.

Activated carbon cloth (ACC), known as Zorflex dressing, has emerged as an innovative approach in managing bacterial infection in diabetic foot ulcer (DFU) treatment. This pilot study was undertaken to determine the efficacy of Zorflex ACC dressing (Chemviron Carbon Cloth Division, UK) compared to standard silver-based dressing on DFUs. An open label, comparative, randomised controlled trial enrolling patients who attended the diabetic foot clinic was conducted between August 2022 and August 2023. The primary endpoint was a difference of 20% in wound area reduction with the ACC dressing compared to silver-based dressing within eight weeks. The secondary endpoints were proportion of complete healing, time to healing and adverse events. The cohort comprised 40 patients. The mean wound reduction percentage at 8 weeks for patients in the ACC arm was 85.40±16.00% compared with 65.08±16.36% in the silver-based dressing arm. Complete healing was observed in six of 20 patients in the ACC arm compared to two of 20 in the silver-based dressing arm. These data suggest that the ACC dressing promotes better ulcer healing in DFU patients than the silver-based dressing.

Prevalence of multidrug-resistant bacterial infections in diabetic foot ulcers: A meta-analysis.

Multidrug-resistant (MDR) bacterial infections have become increasingly common in recent years due to the increased prevalence of diabetic foot ulcers (DFUs). We carried out a meta-analysis aimed at investigating the prevalence of MDR bacteria isolated from DFUs and analysing the risk factors for MDR bacterial infection in patients with DFUs. The PubMed/Medline, Web of Science, Embase, Cochrane Library, Ovid, Scopus, and ProQuest databases were searched for studies published up to November 2023 on the clinical outcomes of MDR bacteria in DFUs. The main outcome was the prevalence of MDR bacteria in DFUs. A total of 21 studies were included, representing 4885 patients from which 2633 MDR bacterial isolates were obtained. The prevalence of MDR bacteria in DFUs was 50.86% (95% confidence interval (CI): 41.92%-59.78%). The prevalence of MDR gram-positive bacteria (GPB) in DFUs was 19.81% (95% CI: 14.35%-25.91%), and the prevalence of MDR gram-negative bacteria (GNB) in DFUs was 32.84% (95% CI: 26.40%-39.62%). MDR Staphylococcus aureus (12.13% (95% CI: 8.79%-15.91%)) and MDR Enterococcus spp. (3.33% (95% CI: 1.92%-5.07%)) were the main MDR-GPB in DFUs. MDR Escherichia coli, MDR Pseudomonas aeruginosa, MDR Enterobacter spp., MDR Klebsiella pneumoniae, and MDR Proteus mirabilis were the main MDR-GNB in DFUs. The prevalence rates were 6.93% (95% CI: 5.15%-8.95%), 6.01% (95% CI: 4.03%-8.33%), 3.59% (95% CI: 0.42%-9.30%), 3.50% (95% CI: 2.31%-4.91%), and 3.27% (95% CI: 1.74%-5.21%), respectively. The clinical variables of diabetic foot ulcer patients infected with MDR bacteria and non-MDR bacteria in the included studies were analysed. The results showed that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization and previous use of antibacterial drugs were significantly different between the MDR bacterial group and the non-MDR bacterial group. We concluded that there is a high prevalence of MDR bacterial infections in DFUs. The prevalence of MDR-GNB was greater than that of MDR-GPB in DFUs. MDR S. aureus was the main MDR-GPB in DFUs, and MDR E. coli was the main MDR-GNB in DFUs. Our study also indicated that peripheral vascular disease, peripheral neuropathy, nephropathy, osteomyelitis, Wagner's grade, previous hospitalization, and previous use of antibacterial drugs were associated with MDR bacterial infections in patients with DFUs.

Potassium permanganate in treatment of diabetic foot ulcer: A randomized clinical trial.

Diabetic foot ulcers (DFU) are a severe complication in diabetes patients, often resulting in significant morbidity and mortality due to non-healing. This study investigated the effectiveness of 5% topical potassium permanganate on these ulcers. A clinical trial was conducted on 23 patients with Wagner grade I and II DFU. Patients in the control group received standard treatment, while those in the intervention group also received 5% potassium permanganate topically. Data were recorded at 0, 7, 14, and 21 days for analysis. Among 23 patients studied, 7 (30.4%) were male and 16 (43.7%) female, with an average age of 59 ± 4 years. Both groups showed a statistically significant decrease in wound size and infection over time (p < 0.001). The intervention group, however, had a more substantial reduction in wound size and infection rate (p < 0.05). Potassium permanganate, when applied topically, is both well-tolerated and effective in enhancing wound healing and reducing infection in DFU, suggesting its potential as a complementary treatment.

Correlation between inflammatory factors, autophagy protein levels, and infection in granulation tissue of diabetic foot ulcer.

To observe the expression of inflammatory factors and autophagy-related proteins in granulation tissue of diabetic foot ulcer (DFU) patients and analyze their relationship with infection. This is a retrospective cohort study. One hundred and fifty-two patients with DFU in our hospital from July 2020 to March 2022 were selected as the DFU group, including 98 cases in infection stage group and 54 cases in infection control group. The patients were further graded as the mild (51 cases), the moderate (65 cases), and the severe infection group (36 cases) according to the Wagner grading criteria. Sixty-seven patients with foot burns during the same period were selected as the control group. The distribution of pathogenic bacteria on the ulcer surface was examined using fully automated bacterial analyzer. The expression of inflammatory factors (procalcitonin [PCT], tumor necrosis factor-α [TNF-α], and interleukin-6 [IL-6]) was valued by real-time fluorescence quantitative PCR (qRT-PCR). Protein expression was measured by immunohistochemistry (IHC). The correlation was analyzed by Pearson. The surface infection of DFU patients was mostly induced by gram-negative and gram-positive bacteria, with Pseudomonas aeruginosa predominating among the Gram-negative bacteria and Staphylococcus aureus among the gram-positive bacteria. The infection stage group had higher content of PCT, TNF-α, and IL-6 and lower content of Beclin-1 and LC3 than the infection control group (p < .001). The levels of PCT, TNF-α, and IL-6 in the DFU patients with cardiovascular events were higher than those in the nonoccurrence group (p < .001). Glycated hemoglobin in patients with DFU was positively correlated with PCT, TNF-α, and IL-6 levels (p < .05), and negatively correlated with Beclin-1 and LC3 levels (p < .001). P. aeruginosa and S. aureus were predominant bacterial in DFU infections. Inflammatory factor and autophagy protein expression were closely correlated with the degree of infection.

L-arginine supplementation abrogates hypoxia-induced virulence of Staphylococcus aureus in a murine diabetic pressure wound model.

Diabetic foot ulcers (DFUs) are the most common complications of diabetes resulting from hyperglycemia leading to ischemic hypoxic tissue and nerve damage. Staphylococcus aureus is the most frequently isolated bacteria from DFUs and causes severe necrotic infections leading to amputations with a poor 5-year survival rate. However, very little is known about the mechanisms by which S. aureus dominantly colonizes and causes severe disease in DFUs. Herein, we utilized a pressure wound model in diabetic TALLYHO/JngJ mice to reproduce ischemic hypoxic tissue damage seen in DFUs and demonstrated that anaerobic fermentative growth of S. aureus significantly increased the virulence and the severity of disease by activating two-component regulatory systems leading to expression of virulence factors. Our in vitro studies showed that supplementation of nitrate as a terminal electron acceptor promotes anaerobic respiration and suppresses the expression of S. aureus virulence factors through inactivation of two-component regulatory systems, suggesting potential therapeutic benefits by promoting anaerobic nitrate respiration. Our in vivo studies revealed that dietary supplementation of L-arginine (L-Arg) significantly attenuated the severity of disease caused by S. aureus in the pressure wound model by providing nitrate. Collectively, these findings highlight the importance of anaerobic fermentative growth in S. aureus pathogenesis and the potential of dietary L-Arg supplementation as a therapeutic to prevent severe S. aureus infection in DFUs.IMPORTANCES. aureus is the most common cause of infection in DFUs, often resulting in lower-extremity amputation with a distressingly poor 5-year survival rate. Treatment for S. aureus infections has largely remained unchanged for decades and involves tissue debridement with antibiotic therapy. With high levels of conservative treatment failure, recurrence of ulcers, and antibiotic resistance, a new approach is necessary to prevent lower-extremity amputations. Nutritional aspects of DFU treatment have largely been overlooked as there has been contradictory clinical trial evidence, but very few in vitro and in vivo modelings of nutritional treatment studies have been performed. Here we demonstrate that dietary supplementation of L-Arg in a diabetic mouse model significantly reduced duration and severity of disease caused by S. aureus. These findings suggest that L-Arg supplementation could be useful as a potential preventive measure against severe S. aureus infections in DFUs.

Lytic activity of phages against bacterial pathogens infecting diabetic foot ulcers

Complications of diabetes, such as diabetic foot ulcers (DFUs), are common, multifactorial in origin, and costly to treat. DFUs are the cause of nearly 90% of limb amputations among persons with diabetes. In most chronic infections such as DFU, biofilms are involved. Bacteria in biofilms are 100–1000 times more resistant to antibiotics than their planktonic counterparts. Multidrug-resistant (MDR) Staphylococcus aureus and Pseudomonas aeruginosa infections in DFUs may require alternative therapeutic agents such as bacteriophages ("phages"). This study describes the lytic activity of phage cocktails AB-SA01 (3-phage cocktail) and AB-PA01 (4-phage cocktail), which target S. aureus and P. aeruginosa, respectively. The host range and lytic effect of AB-SA01 and AB-PA01 on a planktonic culture, single-species biofilm, and mixed-species biofilm were evaluated. In vitro testing showed that 88.7% of S. aureus and 92.7% of P. aeruginosa isolates were susceptible to AB-SA01 and AB-PA01, respectively, in the planktonic state. The component phages of AB-SA01 and AB-PA01 infected 66% to 94.3% of the bacterial isolates tested. Furthermore, AB-SA01 and AB-PA01 treatment significantly (p < 0.05) reduced the biofilm biomass of their hosts, regardless of the antibiotic-resistant characteristics of the isolates and the presence of a non-susceptible host. In conclusion, the strong lytic activity, broad host range, and significant biofilm biomass reduction of AB-SA01 and AB-PA01 suggest the considerable potential of phages in treating antibiotic-resistant S. aureus and P. aeruginosa infections alone or as coinfections in DFUs.

Residential Address Amplifies Health Disparities and Risk of Infection in Individuals With Diabetic Foot Ulcers.

To determine the association between social determinants of health (SDOH) and a diagnosis of diabetic foot ulcer (DFU) infection. Targeted interrogation of electronic health record data using novel search engines to analyze individuals with a DFU infection during a 5-year period (2013-2017) was performed. We extracted geolocated neighborhood data and SDOH characteristics from the National Neighborhood Data Archive and used univariate and multiple logistic regression to evaluate associations with outcomes in the population with diabetes. Among 4.3 million people overall and 144,564 individuals with diabetes seen between 2013 and 2017, 8,351 developed DFU, of which cases 2,252 were complicated by a DFU infection. Sex interactions occurred, as men who experienced a DFU infection more frequently identified as having nonmarried status than their female counterparts. For the population with DFU infection, there were higher rates for other SDOH, including higher neighborhood disadvantaged index score, poverty, nonmarriage, and less access to physician/allied health professionals (all P < 0.01). In multiple logistic regression, those individuals who developed DFU infection came from neighborhoods with greater Hispanic and/or foreign-born concentrations (odds ratio 1.11, P = 0.015). We found significant differences in neighborhood characteristics driving a higher risk for DFU infection in comparisons with the grouping of individuals with diabetes overall, including increased risk for individuals with Hispanic and/or foreign-born immigration status. These data strongly support the need to incorporate SDOH, particularly ethnic and immigration status, into triage algorithms for DFU risk stratification to prevent severe diabetic foot complications and move beyond biologic-only determinants of health.

Virulence characteristics of Gram-positive bacteria isolated from diabetic foot ulcers.

Diabetic wound infections including diabetic foot ulcers (DFUs) are a major global health concern and a leading cause of non-traumatic amputations. Numerous bacterial species establish infection in DFUs, and treatment with antibiotics often fails due to widespread antibiotic resistance and biofilm formation. Determination of bacterial species that reside in DFU and their virulence potential is critical to inform treatment options. Here, we isolate bacteria from debridement tissues from patients with diabetes at the University of Colorado Anschutz Medical Center. The most frequent species were Gram-positive including Enterococcus faecalis, Staphylococcus aureus, and Streptococcus agalactiae, also known as Group B Streptococcus (GBS). Most tissues had more than one species isolated with E. faecalis and GBS frequently occurring in polymicrobial infection with S. aureus. S. aureus was the best biofilm producing species with E. faecalis and GBS isolates exhibiting little to no biofilm formation. Antibiotic susceptibility varied amongst strains with high levels of penicillin resistance amongst S. aureus, clindamycin resistance amongst GBS and intermediate vancomycin resistance amongst E. faecalis. Finally, we utilized a murine model of diabetic wound infection and found that the presence of S. aureus led to significantly higher recovery of GBS and E. faecalis compared to mice challenged in mono-infection.

Guided Conditional Diffusion Classifier (ConDiff) for Enhanced Prediction of Infection in Diabetic Foot Ulcers

Guided Conditional Diffusion Classifier (ConDiff) for Enhanced Prediction of Infection in Diabetic Foot Ulcers