Infected Diabetic Foot Ulcers Research Articles

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.

Lipid Profile Paradox: Investigating Improved Lipid Levels in Diabetic Mellitus Patients with Foot Ulcer Infections—A Prospective Descriptive Study

Type 2 diabetes mellitus (DM) is a chronic metabolic disorder posing multifaceted challenges to global public health. Among its numerous complications, infected diabetic foot ulcers (IDFUs) represent a particularly debilitating consequence. Beyond cardiovascular implications, there is an emerging understanding of the interconnectedness among IDFUs, neuropathy, atherosclerosis, and dyslipidemia. IDFUs, peripheral neuropathy, and atherosclerosis share common risk factors and mechanistic pathways. The primary objective of this study was to characterize the lipid profiles in DM patients with IDFUs, comparing them with DM patients without foot ulcers, and with a control group of healthy subjects. The secondary objectives included evaluating apolipoprotein E (ApoE) levels across these study groups and comparing lipid profiles within IDFU subgroups. A total of 160 patients were assessed for this study. After applying exclusion criteria, 140 participants were included, divided into three groups: Group IDFU (80 patients with IDFUs), Group DM (32 patients with DM but no foot ulcers), and Group Controls (28 healthy controls). Compared to Group DM, Group IDFU demonstrated lower levels of high-density lipoprotein cholesterol (HDL-C) (30.9 ± 12.6 mg/dL vs. 40.8 ± 16.6 mg/dL, p = 0.002), but improved levels of ApoE (160.9 ± 68.4 mg/dL vs. 197.2 ± 69.6 mg/dL, p = 0.01), triglycerides (TG) (126.9 ± 56.2 mg/dL vs. 165.8 ± 79.0 mg/dL, p = 0.004), low-density lipoprotein cholesterol (LDL-C) (84.2 ± 32.3 mg/dL vs. 92.3 ± 39.3 mg/dL, p = 0.1), and total cholesterol (133.6 ± 43 mg/dL vs. 164.6 ± 44.4 mg/dL, p = 0.002). The IDFU patients exhibit improved lipid profiles, excepting HDL-C, which is unusual because IDFU follows complications related to dyslipidemia for DM patients. Anemia, impaired renal function, and elevated TG levels were identified as biomarkers for mortality among patients with IDFUs. The data suggest that a lower level of HDL-C and an improved lipid profile may indicate a systemic end-stage disease manifestation in DM patients with IDFUs.

Theruptor Novo dressing for an infected diabetic foot ulcer: a case study

In diabetes mellitus (DM) patients with peripheral neuropathy, the diabetic foot infection (DFI) often begins with a small wound that patients may not easily detect and then progresses to a more complex wound. Diabetic foot ulcer (DFU) is estimated to occur in approximately in 25% of individuals with diabetes in India. The bacterial infection is one of the important cause for the chronicity of DFU and are accountable for the high medical costs as well as affecting patients’ quality of life significantly. Preventing DFU secondary infections is an important function of wound dressing. There are many wound dressings available for DFU, and choosing the right dressing is one of the important parameter in the management and ultimately preventing the limb amputation. In this case, the patient presented with non-healing infected DFU and we used Theruptor Novo dressings for the wound management. The Theruptor Novo dressing was efficient in exudate management and preventing secondary infection which helped in accelerated DFU healing.

Distribution of multidrug-resistant bacterial infections in diabetic foot ulcers and risk factors for drug resistance: a retrospective analysis.

To investigate the distribution, drug resistance and risk factors of multi-drug resistant bacterias (MDROs) in patients with Type 2 diabetic foot ulcers (DFU). The clinical data, foot secretions, pathogenic microorganisms and drug sensitivity tests of 147 patients with type 2 diabetes admitted to our department from January 2018 to December 2021 were analyzed. Patients were divided into two groups according to whether they had been infected with MDROs or not. Seventy-one cases were infected with MDROs as the case group, and the remaining 76 cases were the control group. Chi-square test and t-test were used to analyze the results of MDROs infection and DFU, and logistic multivariate regression was used to evaluate the risk factors of MDROs infection. A total of 71 strains were isolated from the MDROs-positive group, with the top three being Staphylococcus aureus (46.48%), Escherichia coli (22.53%), and Pseudomonas aeruginosa (18.31%), respectively. Logistic multifactorial regression analysis showed that history of previous antimicrobial exposure, neuroischemic wound, Wagner grade 3-5, and combined osteomyelitis were associated with Type 2 diabetic foot infection MDROs (P<0.05). Previous history of antimicrobial exposure, neuroischemic wounds, Wagner grade 3-5, and combined osteomyelitis are independent risk factors for MDROs, which can identify the risk factors for MDROs at an early stage and help to identify people at high risk of MDROs infection and take relevant comprehensive treatment in time to slow down the development of the disease.

Community-associated methicillin-resistant Staphylococcus aureus infection of diabetic foot ulcers in an eastern diabetic foot center in a tertiary hospital in China: a retrospective study

BackgroundDiabetic foot concerns are a major public health problem. Methicillin-resistant Staphylococcus aureus (MRSA) plays a significant role in diabetic foot ulcers. Community-associated MRSA has become notorious for skin and skin soft tissue infections over the last two decades. This study investigated MRSA infection in diabetic foot patients at a tertiary hospital, focusing on the epidemiology and characteristics of community-associated MRSA.MethodsA total of 149 patients with diabetic foot infection whose culture results indicated Staphylococcus aureus as the source were selected. Epidemiological investigations, clinical characteristics, laboratory index records, antibiotic susceptibility analysis, and clinical outcome tracking were performed in all cases. Based on oxacillin resistance using the Vitek Compact 2 system, cases were divided into methicillin-sensitive Staphylococcus aureus and MRSA groups. Subgroup analysis of the MRSA group was performed in accordance with the Centers for Disease Control definition: community-associated MRSA and hospital-associated MRSA.ResultsThe MRSA group (n = 41, 27.5%) had a longer duration of ulcers and hospital stay and higher hospitalization costs than the methicillin-sensitive Staphylococcus aureus group (n = 108, 72.5%). According to the classification criteria of Infectious Diseases Society of America, the severity of infection in the community-associated MRSA group was higher than that in the hospital-associated MRSA group. The analysis of antimicrobial susceptibility of 41 MRSA isolates showed that the resistance rates to erythromycin, clindamycin, quinolone, gentamicin, tetracycline, and rifampicin were 78.0%, 68.3%, 31.7%, 17.1%, 9.8%, and 2.4%, respectively. All the MRSA strains were sensitive to linezolid, tigecycline, and vancomycin. The resistance rates to quinolones and gentamycin in the community-associated MRSA group (both 0%) were lower than those in the hospital-associated MRSA group.ConclusionEmergence of MRSA in diabetic foot ulcer was associated with a prolonged wound duration and increased consumption of medical resources. Community-associated MRSA strains predominated among MRSA isolates from diabetic foot wounds and caused more severe infections.

Empirical Antibiotic Therapy in Diabetic Foot Ulcer Infection Increases Hospitalization.

We evaluated the outcomes associated with initial antibiotic management strategies for infected diabetic foot ulcers (DFUs) diagnosed in an outpatient multidisciplinary center. Consecutive outpatient individuals with infected DFUs, stratified according to Infectious Diseases Society of America infection severity, were followed for 1 year from the initial antibiotic administration to treat acute infection. The main outcomes were hospitalization rates for a diabetes-related foot complication within 30 days of diagnosis and requiring an amputation or death during follow-up. Outcomes were analyzed by regression analysis, accounting for demographics, clinical characteristics, and antibiotic therapy. Among 147 outpatients with infected DFUs, 116 were included. Infections were categorized as mild (68%), moderate (26%), and severe (6%). Empirical antibiotics (not culture-guided) were prescribed as initial treatment in 39 individuals, while 77 received culture-based antibiotics. There were no differences in demographic or clinical characteristics between the antibiotic administration groups, except for a higher body mass index and prevalence of chronic kidney disease in the empirical cohort. Forty-two infected DFU patients required hospitalization within 30 days of diagnosis for the same reason. The relative risk for hospitalizations was 1.87 greater in those with mild infections when treated with empirical antibiotics compared with culture-directed antibiotics. There were no differences in amputations and/or death at 1 year follow-up. These data support obtaining tissue culture to guide antibiotic therapy, regardless of DFU infection severity, to decrease hospitalizations.

Patterns of Pathogens and Antimicrobial Susceptibility Profiles in Diabetic Foot Ulcers’ Infections among Patients at Bugando Medical Centre in Mwanza, Tanzania

Background: Diabetic foot ulcer (DFU) is an open sore or wound on the foot of a person with diabetes, and is most commonly located on the plantar surface, or bottom of the foot. The defect is relatively common in adult and elders with diabetes mellitus. Infected lower extremities wound with multi-drug resistant bacteria usually are associated with increased morbidity, mortality and long-term disabilities among diabetic patients. Although the burden of DFU is known in Tanzania (and Mwanza in particular), there is limited information on the patterns of pathogens associated with DFU in our setting, on bacterial and fungal pathogens which in turn limit specific management options to these patients. Methodology: Analytical cross section hospital-based study was conducted among patients with DFU admitted or attending outpatient clinics at BMC from May to July 2022. A structured questionnaire was used to collect socio-demographic, clinical and laboratory data from patients with DFU. Tissue culture was obtained from the base of the ulcer after cleaning with normal saline followed by removing of cellular debris and normal flora over the lesion. Finally, the obtained samples were subjected to culture methods to identify the presence of pathogens (bacteria and fungi) and antimicrobial susceptibility profiles of bacteria. Result: During the study period and based on inclusion criteria, a total of 71 patients, with a mean age of 59.2 ± 13.0 years were recruited. The majority of the participants were male 47 (66.2%). A total of 60 (84.5%) samples were culture positive, resulting into a total of 92 microorganisms isolated. More than half of cultures 34 (56.7%) revealed the presence of single microorganisms. Pathogens isolated were both bacterial 70 (76.1%) and fungi species 22 (23.9%), all bacterial isolates were aerobic. P. aeruginosa and E. coli were most frequent isolated gram-negative bacteria 12(23.5%) and 9(17.6%) respectively. On other hand common isolated gram-positive strains were S. aureus 13 (68.4%) out of all 19 gram-positive culture isolates. A total of 22 fungi spp were isolated, among them 7 (31.8%) were yeast C. albicans 3 (42.8%), A. fumigatus were frequent isolated 13 (86.7%). Polymicrobial growth was observed in 43.3% samples against 56.7% of monomicrobial growth. Most prevalent gram-negative bacteria Pseudomonas aeruginosa showed low resistance to ciprofloxacin, meropenem, gentamicin, piperacillin tazobactam (7.1%, 21.4%, 21.4% and 21.4 respectively) but more resistant to cephalosporins. Staphylococcus aureus showed low resistance to ciprofloxacin, gentamicin and clindamycin (30.8%, 15.4%, and 38.5% respectively), Total MDR bacteria isolates were 64.3%, where methicillin resistance staphylococcus aureus (MRSA) were 76.9%. More than 85.7% of the patient with higher grade ulcer, stage 3 and 4 according to Wagner’s classification were positive to diabetic foot infection and 14.3% of patients with Wagner’s stage 3 and 4 were not infected on their ulcers. Conclusion: Gram negative bacteria were most commonly isolated than gram positive bacteria in causing DFU infections. For gram negative spp the most effective antibiotic were ciprofloxacin, gentamicin, piperaccilin tazobactam and meropenem. Third generation cephalosporins, amoxicillin clavulanate showed poor effectiveness. All cases of DFU infection should therefore be subjected to culture and antimicrobial sensitivity testing for targeted infection management. More studies involving anaerobic pathogens and antifungal susceptibility patterns

Poly(pentahydropyrimidine)‐Based Hybrid Hydrogel with Synergistic Antibacterial and Pro‐Angiogenic Ability for the Therapy of Diabetic Foot Ulcers

AbstractBacterial infection and impaired angiogenesis make the treatment of diabetic foot ulcers (DFU) extremely challenging. Cationic polymers are expected to treat infected wounds due to their excellent antibacterial properties, but still, it is difficult to meet the therapeutic needs of pro‐angiogenesis and anti‐infections due to their simple construction units and outmoded synthesis methods. Herein, a cationic poly(pentahydropyrimidine) (PPHP) library with strong modifiability is synthesized to construct a hybrid hydrogel with synergistic therapeutic effects for the treatment of infected DFUs. It is found that the as‐synthesized hybrid hydrogel can up‐regulate angiogenesis‐related gene (HIF‐1, VEGF, and bFGFR/bFGF) expression and targeted disruption of bacterial cell membranes, which finally promotes the healing of infected DFU (wound healing rate: 92%) within 10 days. This hydrogel, thus, holds great promise in developing new strategies to significantly enhance the treatment of DFU and other bacterial‐infected pathological diagnoses.

Gene expression levels of inflammatory mediators in diabetic foot ulcer patients

Background: Diabetic foot ulcer (DFU) is a common serious complication of diabetes. Nowadays there is a suggestion that referred to the fact&#x0D; the chronicity of DFU is a result of the positive feedback of proinflammatory cytokines production. Objective: This study aimed to display the negative effects of persistent expression of proinflammatory cytokines of (IL-1β and IL-18) under hyperglycemic condition on the DFU microenvironment and clarify the role of growth factor Milk fat globule-epidermal growth factor- 8( MFG-) in the DFU healing process. Approach: Clinical data of a total of 49 type 2 diabetic patients have chronic diabetic foot ulcer grade 2 and 3 (infected DFU n= 29 and non-infected n=21) in addition to the control group (n=25) were participated in the study since June 2021 to April 2022 , venous blood samples were collected for the measurement of the gene expression levels of (IL-1β ; IL-18 and MFG-E8) by Real-Time PCR technique . Results: There was no significant difference in age and sex when compared with the control group at p= 0.798, p =0.514 respectively. High levels of gene expression of (IL-1β ; IL-18 and MFG-E8) were shown in the patients group in comparison to the healthy control.&#x0D; Conclusions: Current data confirmed that the inflammatory mediators’ (IL-1β ; IL-18 and MFG-E8) have a strong association with the pathogenesis of DFU healing process.&#x0D; &#x0D; &#x0D;

The Prevalence of Anemia in Hospitalized Patients With Diabetic Foot Ulcer (DFU) and the Relationship Between the Severity of Anemia and the Severity of DFU.

We aim to determine the prevalence of anemia in hospitalized patients with diabetic foot ulcers (DFUs) and estimate the relationship between the severity of anemia and diabetic foot ulcer. We retrospectively collected and evaluated the data of 323 patients hospitalized with diabetic foot ulcer (DFU). We included 299 type 2 diabetic patients with foot ulcers of neuropathic or neuroischemic nature with infection. Anemia was defined based on World Health Organization (WHO) criteria, and the severity of DFU was classified in University of Texas (UT) grades. Anemia was detected in 94.3% of DFU, and the prevalence of mild, moderate, and severe anemia was 16.7%, 55.7%, and 27.6%, respectively. There was a significant difference in the mean hemoglobin (Hb) levels among the patients with varying grades of severity of DFU (1B: Hb=10.17±2.08 gm/dL, 2B: Hb=9.27±2.04 gm/dL, 3B: Hb=8.03±1.829 gm/dL;p value=<0.0001). The iron study was available in 141 (47.15%)patients and was suggestive of anemia of chronic disorder (mean serum iron=40.22±23.81 mcg/dL, mean total iron-binding capacity (TIBC)=239.34±67.24 mcg/dL, mean ferritin=378.05±141.337 ng/mL). TIBC significantly decreased (1B=262.13±61.05, 2B=233.65±71.26, 3B=222.43±74.18; p=0.04), and ferritin significantly increased (1B=309.9±70.76, 2B=351.73±94.22, 3B=488.58±170.4; p<0.0001) with increasing DFU severity. Hemoglobin was significantly decreased at the time of discharge in comparison to that at admission (9.3±2.1 gm/dL versus 8.8±1.5 gm/dL;p value=0.01). Red blood cell (RBC) counts, mean corpuscular volume (MCV), mean corpuscular hemoglobin concentration (MCHC), lymphocyte counts, albumin, calcium, and high-density lipoprotein (HDL) significantly decreased with the increase of DFU severity. The duration of hospitalization, total leucocyte counts, neutrophil counts, and neutrophil-to-lymphocyte ratio (NLR) increased with the severity of DFU. The prevalence of anemia was very high in DFU and more than three-fourths of the patients had moderate to severe anemia. The severity of anemia was associated with the severity of DFU. The most common cause of anemia was anemia of chronic disorder secondary to diabetic foot infection. During the period of hospitalization, hemoglobin decreased despite improvement in DFU infection.