Infected Diabetic Foot Ulcers Research Articles

Risk Factors for Multidrug-Resistant Bacterial Infection in Diabetic Foot Ulcers.

This study aimed to analyze the distribution of multidrug-resistant (MDR) organisms (MDROs) in patients with diabetic foot ulcers (DFUs) and to identify risk factors for MDRO infections. Patients hospitalized with DFUs were enrolled, and ulcer swabs were cultured for bacterial identification and antibiotic susceptibility testing. Hematology and blood biochemistry were also assessed. A total of 228 patients hospitalized with DFUs were enrolled. Out of 150 patients with positive cultures, 123 (82%) were infected with single strains, whereas 27 (18%) had mixed infections. Out of the 177 bacterial strains isolated, 78 (44%) were MDROs. Among the top 5 most common bacteria, coagulase-negative Staphylococcus, Staphylococcus aureus, and Proteus exhibited MDR rates of 92%, 56%, and 55%, respectively. Pseudomonas aeruginosa and Enterobacter cloacae had low MDR rates of 5% and 8%, respectively. Single variable logistic regression analysis showed that neutrophil percent (NEU%), creatinine, C-reactive protein, and fasting plasma glucose (FPG) were risk factors for MDRO infection, whereas hemoglobin and albumin levels were protective factors. Multivariable logistic regression analysis revealed that NEU% and FPG were independent risk factors for MDRO infection. A high percentage of the infections in patients with DFUs were caused by MDROs. To reduce MDRO infections in high-risk patients, it is important to use antibiotics rationally, improve patients' FPG levels and nutritional status, and strengthen hospital sterilization processes.

Clinic-mycological spectrum of Candida infection in diabetic foot ulcers in a tertiary care hospital.

In diabetic foot ulcers, if fungal agents, such as Candida species penetrate the cutaneous or depth of the ulcer, it can increase the wound severity and make it more difficult to heal. A cross-sectional study was performed on 100 diabetic patients with a foot ulcer from December 2019 to November 2020 in northern Iran. Patient data and wound grades were recorded in a questionnaire. Candida infection was confirmed by direct microscopic examination and culture. To identify the causative agent, polymerase chain reaction-restriction fragment length polymorphism using MspI enzyme and the partial amplification of hyphal wall proteins (HWP1) gene were performed. Mean age of the participants was 62.1 ± 10.8 years old, and 95% of them had type 2 diabetes. Moreover, more than 83% of them had diabetes for a duration of 10 years. In addition, 59% of the patients were male, and 66% > of them had poor education levels. Besides, 99% of them were married, and 52% were rural. Furthermore, 95% of the participants had neuropathic symptoms and 88% used antibiotics. The HbA1C level was > 9% in 69% of them, and the mean ulcer grade of the patients was 2.6±1.05. Candida infection was detected in 13% of the deep tissue and 7% of the tissue surrounding the wound. The predominant Candida isolate was C. parapsilosis (71.5%) and C. albicans (14.3%). Infections caused by filamentous fungi were not detected. There was a statistically significant relationship between Candida infection and gender, rural lifestyle, HbA1C, and ulcer grade. Mycological evaluations of diabetic foot ulcers are often ignored. The present study revealed that C. parapsilosis is the most common causative agent of deep-seated foot ulcer infection in these patients and may require specific treatment. Therefore, more attention of physicians to Candida infections, early diagnosis, and prompt treatment can help accelerate wound healing and prevent amputation.

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.

Pentraxin-3 and Other Inflammatory Markers for an Infected Diabetic Foot Ulcer Diagnosis: A Prospective Study.

Strategies have been researched and implemented to reduce the number of people with diabetic foot ulcers (DFUs). One problem is the accurate assessment of DFU severity, which is the main factor in resource allocation and treatment choice. The primary objective of this study was to assess pentraxin-3 as a biomarker of an infected DFU (IDFU), the limb amputation level prognosis, and patient survival. The secondary objectives were to evaluate and compare other markers, including white blood cells (WBCs), C-reactive protein (CRP), the erythrocyte sedimentation rate (ESR), and procalcitonin (PCT), for identifying IDFUs. Over a period of two years, 145 patients were followed; 131 of these were analyzed for this study. Pentraxin-3 was found to be a good predictor of death (p = 0.047). A comparison between IDFUs and DFUs revealed the following differences: PCT had the highest AUROC of 0.91, sensitivity of 93.7, and specificity of 83.3%. CRP had a cutoff value of 226 mg/L, an AUROC of 0.89, a sensitivity of 95.5%, and a specificity of 83.3%. Fibrinogen had an AUROC of 0.87 at a cutoff value of 5.29 g/L, with a good sensitivity and specificity of 85% and 87%, respectively. ESR had a cutoff value of 46 mm/h, an AUROC of 85%, a sensitivity of 83.7%, and a specificity of 83.3%. Pentraxin-3 showed promising results in predicting IDFUs and DFUs, and it served as a marker for the risk of death in IDFU patients during the 6 month follow-up. Other markers, including CRP, PCT, ESR, and fibrinogen, were more effective in differentiating between IDFUs and DFUs.

Preclinical study of diabetic foot ulcers: From pathogenesis to vivo/vitro models and clinical therapeutic transformation.

Diabetic foot ulcer (DFU), a common intractable chronic complication of diabetes mellitus (DM), has a prevalence of up to 25%, with more than 17% of the affected patients at risk of amputation or even death. Vascular risk factors, including vascular stenosis or occlusion, dyslipidemia, impaired neurosensory and motor function, and skin infection caused by trauma, all increase the risk of DFU in patients with diabetes. Therefore, diabetic foot is not a single pathogenesis. Preclinical studies have contributed greatly to the pathogenesis determination and efficacy evaluation of DFU. Many therapeutic tools are currently being investigated using DFU animal models for effective clinical translation. However, preclinical animal models that completely mimic the pathogenesis of DFU remain unexplored. Therefore, in this review, the preparation methods and evaluation criteria of DFU animal models with three major pathological mechanisms: neuropathy, angiopathy and DFU infection were discussed in detail. And the advantages and disadvantages of various DFU animal models for clinical sign simulation. Furthermore, the current status of vitro models of DFU and some preclinical studies have been transformed into clinical treatment programs, such as medical dressings, growth factor therapy, 3D bioprinting and pre-vascularization, Traditional Chinese Medicine treatment. However, because of the complexity of the pathological mechanism of DFU, the clinical transformation of DFU model still faces many challenges. We need to further optimize the existing preclinical studies of DFU to provide an effective animal platform for the future study of pathophysiology and clinical treatment of DFU.

Serum Procalcitonin (PCT) - Is there a Role as an Early Biomarker in Infected Diabetic Foot Ulcer (IDFU) Patients?

Infected diabetic foot ulcers may lead to serious complications if not recognised in the early stage. Diagnosis of infection is particularly challenging at that stage; thus, a sensitive inflammatory biomarker may be helpful. We aimed to evaluate the role of procalcitonin (PCT) as an early biomarker for infected diabetic foot ulcers (IDFU). This cross-sectional study was conducted at Klinik Rawatan Keluarga (KRK), Orthopedic clinic and wards in Hospital Universiti Sains Malaysia (USM) from May 2020 to December 2020. A total of 264 participants were recruited and divided into three groups: 50 diabetic patients with no ulcers (control), 107 patients with non-infected diabetic foot ulcers (NIDFU), and 107 patients with infected diabetic foot ulcers (IDFU). The level of PCT was taken for all patients. Total white count (TWC) and C-reactive protein (CRP) were taken only for IDFU patients. Diagnosis of infection was based on the Infectious Disease Society of America-International Working Group of Diabetic Foot (IDSA-IMWGDF), and the severity of infection was graded according to the Wagner Classification. The level of PCT was higher in IDFU than in NIDFU and diabetic patient, with a median (IQR) of 0.355 (0.63) ng/mL, 0.077 (0.15) ng/mL and 0.028 (0.02) ng/mL, respectively. PCT and CRP showed moderate positive correlations in IDFU patients (p<0.001). The sensitivity and specificity were 63.6% and 83.2%, respectively, at the best cut-off at 0.25 ng/mL. PCT is a valuable biomarker for the diagnosis of infection; however, it adds little value in the early diagnosis of IDFU in view of its low sensitivity.

Transcriptomic identification of genes expressed in invasive S. aureus diabetic foot ulcer infection.

Infection in diabetic foot ulcers (DFUs) is one of the major complications associated with patients with diabetes. Staphylococcus aureus is the most common offending pathogen in patients with infected DFU. Previous studies have suggested the application of species-specific antibodies against S. aureus for diagnosis and monitoring treatment response. Early and accurate identification of the main pathogen is critical for management of DFU infection. Understanding the host immune response against species-specific infection may facilitate diagnosis and may suggest potential intervention options to promote healing infected DFUs. We sought to investigate evolving host transcriptome associated with surgical treatment of S. aureus- infected DFU. This study compared the transcriptome profile of 21 patients with S. aureus- infected DFU who underwent initial foot salvage therapy with irrigation and debridement followed by intravenous antibiotic therapy. Blood samples were collected at the recruitment (0 weeks) and 8 weeks after therapy to isolate peripheral blood mononuclear cells (PBMCs). We analyzed the PBMC expression of transcriptomes at two different time points (0 versus 8 weeks). Subjects were further divided into two groups at 8 weeks: healed (n = 17, 80.95%) versus non-healed (n = 4, 19.05%) based on the wound healing status. DESeq2 differential gene analysis was performed. An increased expression of IGHG1, IGHG2, IGHG3, IGLV3-21, and IGLV6-57 was noted during active infection at 0 weeks compared with that at 8 weeks. Lysine- and arginine-rich histones (HIST1H2AJ, HIST1H2AL, HIST1H2BM, HIST1H3B, and HIST1H3G) were upregulated at the initial phase of active infection at 0 weeks. CD177 and RRM2 were also upregulated at the initial phase of active infection (0 weeks) compared with that at 8 weeks of follow-up. Genes of heat shock protein members (HSPA1A, HSPE1, and HSP90B1) were high in not healed patients compared with that in healed patients 8 weeks after therapy. The outcome of our study suggests that the identification of genes evolution based on a transcriptomic profiling could be a useful tool for diagnosing infection and assessing severity and host immune response to therapies.

Basic haematological tests as inflammatory performance markers of patients treated either by conservative surgery or minor amputation for infected diabetic foot ulcers.

Basic inflammatory markers have been extensively studied to differentiate between non-infected and infected diabetic foot ulcers (DFUs). Very rarely, basic haematological tests such as white cell count (WCC) and platelet counts were used as performance markers for DFU infection severity. The aim is to investigate these biomarkers in patients with DFU treated exclusively with surgery. In this retrospective comparative study, we included 154 procedures comparing a conservative surgery group (n = 66 for infected DFU) and a minor amputation group (n = 88 for infected DFU with osteomyelitis). Outcomes were set as the preoperative values of: WCC, neutrophils (N), lymphocytes (L), Monocytes (M), Platelets (P), red cell distribution width (RDW) and the ratios N/L, L/M and P/L. Area under curve (AUC) of the receiver operating characteristic (ROC) was calculated based on the diagnosis of minor amputation as a positive result. Cutoff point values with the highest sensitivity and specificity were obtained for each outcome. The highest AUC values were for WCC (0.68), neutrophils (0.68), platelets (0.7) and P/L ratio (0.69) with corresponding cut-off values of 10,650/mm3 , 76%, 234,000/mcL and 265, respectively. The highest sensitivity was for the platelet count (81.5%) while the highest specificity was for L/M (89%) and P/L ratios (87%). Postoperative values showed similar results. Simple routine blood tests could serve as inflammatory performance markers to help predict the severity of infection in patients treated surgically for infected DFU.

Immersion of debrided diabetic foot ulcer tissue in electrochemically generated pH neutral hypochlorous acid significantly reduces the microbial bioburden: whole-genome sequencing of Staphylococcus aureus, the most prevalent species recovered

Diabetic foot ulcer infections (DFUIs) are the leading cause of lower-limb amputations, mediated predominantly by Staphylococcus aureus. pH-neutral electrochemically generated hypochlorous acid (anolyte) is a non-toxic, microbiocidal agent with significant potential for wound disinfection. To investigate both the effectiveness of anolyte for microbial bioburden reduction in debrided ulcer tissues and the population of resident S.aureus. Fifty-one debrided tissues from 30 people with type II diabetes were aliquoted by wet weight and immersed in 1- or 10-mL volumes of anolyte (200parts per million) or saline for 3min. Microbial loads recovered were determined in colony forming units/g (cfu/g) of tissue following aerobic, anaerobic and staphylococcal-selective culture. Bacterial species were identified and 50S.aureus isolates from 30 tissues underwent whole-genome sequencing (WGS). The ulcers were predominantly superficial, lacking signs of infection (39/51, 76.5%). Of the 42/51 saline-treated tissues yielding ≥105cfu/g, a microbial threshold reported to impede wound-healing, only 4/42 (9.5%) were clinically diagnosed DFUIs. Microbial loads from anolyte-treated tissues were significantly lower than saline-treated tissues using 1mL (1065-fold, 2.0 log) and 10mL (8216-fold, 2.1 log) immersion volumes (P<0.0005). S.aureus was the predominant species recovered (44/51, 86.3%) and 50 isolates underwent WGS. All were meticillin susceptible and comprised 12 sequence types (STs), predominantly ST1, ST5 and ST15. Whole-genome multi-locus sequence typing identified three clusters of closely related isolates from 10 patients indicating inter-patient transmission. Short immersions of debrided ulcer tissue in anolyte significantly reduced microbial bioburden: a potential novel DFUI treatment.

Clinical and Bacteriological Analyses of Biofilm-Forming Staphylococci Isolated from Diabetic Foot Ulcers.

Diabetes mellitus is a chronic disease that is associated with increased morbidity and mortality. Unfortunately, foot ulcers and amputations due to diabetes are very common in developing countries. The purpose of this study was to characterize the clinical presentation of diabetic foot ulcer (DFU) infections, isolate the causative agent, and analyze the biofilm formation and distribution of biofilm-related genes among isolated Staphylococci. The study included 100 diabetic patients suffering from DFUs attending Assiut University Hospital. Swabs were collected and antimicrobial susceptibility testing of the isolates was performed. Biofilm formation was tested phenotypically among staphylococcal isolates and the frequency of different biofilm genes was analyzed by PCR. Clinical presentations of diabetic foot ulcers were correlated with bacterial genetic characteristics. Spa types were determined using DNA Gear-a software. Microbiological analysis showed that 94/100 of the DFUs were positive for bacterial growth. The majority of infections were polymicrobial (54%, n=54/100). Staphylococci were the most commonly detected organisms, of which S. aureus represented 37.5% (n=24/64), S. haemolyticus 23.4% (n=15/64), S. epidermidis 34.3% (n=22/64) and other CNS 4.7% (n=3/64). Interestingly, co-infection with more than one species of Staphylococci was observed in 17.1% (n=11/64) of samples. A high level of antibiotic resistance was observed, where 78.1% (n=50/64) of Staphylococci spp were multidrug-resistant (MDR). Phenotypic detection showed that all isolated Staphylococci were biofilm-formers with different grades. Analysis of biofilm-forming genes among Staphylococci showed that the most predominant genes were icaD, spa, and bap. Isolates with a higher number of biofilm-related genes were associated with strong biofilm formation. Sequencing of the spa gene in S. aureus showed that our isolates represent a collection of 17 different spa types. The majority of DFUs in our hospital are polymicrobial. Staphylococci other than S.aureus are major contributors to infected DFUs. MDR and biofilm formation are marked among isolates, which is paralleled by the presence of different categories of virulence-related genes. All severely infected wounds were associated with either strong or intermediate biofilm formers. The severity of DFU is directly related to the number of biofilm genes.

A study on bacteriological profile and prescription pattern of antibiotics in the management of diabetic foot ulcers in a tertiary healthcare teaching hospital

Infection of diabetic foot ulcers is the most common cause of hospitalization among diabetic patients. If not treated properly in time, the infection will eventually lead to septicemia, amputation and even death. It is found that more than 40 percent of amputations can be prevented by the appropriate treatment of diabetic foot ulcers. Irrational antibiotic use leads to treatment failure adverse drug reactions, superinfections, prolongation of treatment, increased cost and development of antibiotic resistance. Study of the bacteriological profile, antimicrobial susceptibility and prescription pattern aids in evaluating the rationality of antibiotic therapy and promote rational drug use and quality of life of patients. Aims and objectives: To study the prevalence and antibiogram of causative organisms, and the prescription pattern of antibiotics used in the treatment of diabetic foot infection. Methodology: The retrospective study is conducted for a period of 6 months. Case records of 210 patients were selected based on the study criteria. A suitably designed data collection form was used to collect the required data. Statistical analysis was done using Microsoft Excel. Results: Males (77.6%) were more prone to diabetic foot infections. Hypertension (42%) was the most common comorbidity. Staphylococcus aureus (16%) was the most frequently isolated bacteria and most of the infections were monomicrobial (63.8%). Cephalosporin class of antibiotics (34.6%) were most commonly prescribed. Clindamycin (26.6%) was the commonest empirical antibiotic. Out of 273 bacterial isolates, 229 isolates showed resistance to one or more antibiotics. Conclusion: Since there is no antibiotic except for Tigecycline which is 100% sensitive in both Gram-negative and Gram-positive bacteria, it is recommended to prescribe a combination of highly effective antibiotics for empirical therapy.

Application of antibiotic bone cement in the treatment of infected diabetic foot ulcers in type 2 diabetes

BackgroundIn this study, we try to investigate the effect of antibiotic bone cement in patients with infected diabetic foot ulcer (DFU).MethodsThis is a retrospective study, including fifty-two patients with infected DFU who had undergone treated between June 2019 and May 2021. Patients were divided into Polymethylmethacrylate (PMMA) group and control group. 22 patients in PMMA group received antibiotic bone cement and regular wound debridement, and 30 patients in control group received regular wound debridement. Clinical outcomes include the rate of wound healing, duration of healing, duration of wound preparation, rate of amputation, and frequency of debridement procedures.ResultsIn PMMA group, twenty-two patients (100%) had complete wound healing. In control group, twenty-eight patients (93.3%) had wound healing. Compared with control group, PMMA group had fewer frequencies of debridement procedures and shorter duration of wound healing (35.32 ± 3.77 days vs 44.37 ± 7.44 days, P < 0.001). PMMA group had five minor amputation, while control group had eight minor amputation and two major amputation. Regarding the rate of limb salvage, there was no limb lose in PMMA group and two limb losses in control group.ConclusionThe application of antibiotic bone cement is an effective solution for infected DFU treatment. It can effectively decreased the frequency of debridement procedures and shorten the healing duration in patients with infected DFU.