Chronic wounds are difficult to heal due to pathogenic microbial colonization and dysregulation of healing cascades, necessitating novel therapeutic strategies. This study developed a multifunctional nanosystem by integrating the antimicrobial peptide LL37 with cationic polyaminoglycoside (SS-HPT), constructing a self-sustaining "AMP factory" to achieve multi-stage modulation of the wound healing. Validation through cell-level experiments and in vivo dual models (mechanical injury and bacterial infection) in immunocompromised rats demonstrated the system's unique dual intracellular-extracellular pathogen-killing capability, significantly accelerating the wound healing process. Transcriptomic analysis revealed that its mechanism involves the dual effects of suppressing pro-inflammatory factor expression and activating tissue repair pathways. Histological evidence confirmed that the system promotes angiogenesis, enhances re-epithelialization rates, and guides orderly collagen fiber deposition. This nanosystem, combining efficient AMP delivery and integrated therapeutic strategies, achieves three-dimensional synergy in microbial clearance, immune microenvironment regulation, and tissue matrix remodeling, providing theoretical and technical foundations for a paradigm shift in chronic wound treatment.

Few studies have addressed the interaction of specific pathogens with clinical outcomes in patients with diabetic foot infection (DFI). Our study aim was to compare the clinical outcomes among patients with DFI caused by methicillin-resistant Staphylococcus aureus (MRSA) with cases caused by methicillin-sensitive Staphylococcus aureus (MSSA). We gathered the data of 75 consecutive patients admitted at specialized outpatients diabetic with mild or moderate DFI in which S. aureus was isolated from bone or soft tissue specimens in pure or as a part of the polymicrobial culture. Patients were divided into two groups: those with MRSA infection and those with MSSA infection. Patients with MRSA diabetic foot infections were significantly associated with male gender (86% vs. 64%, P = .029), higher SINBAD Classification Score (3.6 ± 0.99 points vs. 2.8 ± 1.06 points, P = .001), longer mean wound evolution [17.8 (3;29.5) weeks versus 9.1 (1;12) weeks, P = .008], bone involvement [18 (50%) versus 9 (23.1%), P = .015] and longer mean healing time [18.2(8;28) weeks versus 9.1 (1;12) weeks, P = .008]. In addition, male gender (OR 8.81, 95% CI 2.00-38.84) and SINBAD Classification Score (OR 2.70, 1.46-5.00) were identified as independent risk factors for MRSA DFI. Significant differences in the number of surgical procedures to resolve infection [15 (41.7%) versus 13 (33.3%), P = .456] or in the mean healing time after surgical treatment [10.5 weeks (6.7;16.5) versus 6.1 weeks (3;8.7), P = .068] were not observed among groups, suggesting that when treatment is based on early and surgical debridement, MRSA infections are not associated with worse prognosis. In conclusion MRSA DFI has importance in clinical outcomes such as time to healing. We propose that recent lines of research regarding the genetic virulence of strains of S. aureus could provide new insights into our results.

This study presents a comprehensive investigation into the microbial ecology of diabetic foot infections (DFIs), using molecular-polymerase chain reaction (PCR) analysis to accurately identify the causative agents. One hundred DFI patients were recruited and classified using the Depth Extent Phase and Associated Etiology (DEPA) score according to their severity. Results revealed polymicrobial infections in 75% of cases, predominantly featuring Staphylococcus epidermidis (83%) and Staphylococcus aureus (63%). Importantly, 20% of samples exhibited facultative anaerobes Bacteroides fragilis or Clostridium perfringens, exclusively in high DEPA score ulcers. Candida albicans coinfection was identified in 19.2% of cases, underscoring the need for mycological evaluation. Empirical antimicrobial therapy regimens were tailored to DEPA severity, yet our findings highlighted a potential gap in methicillin-resistant Staphylococcus aureus (MRSA) coverage. Despite an 88% prevalence of methicillin-resistant Staphylococci, vancomycin usage was suboptimal. This raises concerns about the underestimation of MRSA risk and the need for tailored antibiotic guidelines. Our study demonstrates the efficacy of molecular-PCR analysis in identifying diverse microbial communities in DFIs, influencing targeted antibiotic choices. The results advocate for refined antimicrobial guidelines, considering regional variations in microbial patterns and judiciously addressing multidrug-resistant strains. This research contributes crucial insights for optimizing DFIs management and helps the physicians to have a fast decision in selection the suitable antibiotic for each patient and to decrease the risk of bacterial resistance from the improper use of broad-spectrum empirical therapies.

Peripheral blood mononuclear cells (PB-MNCs) therapy is an adjuvant treatment for patients with ischaemic diabetic foot ulcers (DFUs) and no-option critical limb ischemia (NO-CLI). This study aimed to evaluate factors influencing the effectiveness of PB-MNC therapy.

This prospective, not controlled study included a cohort of patients with DFUs and NO-CLI treated by PB-MNCs. NO-CLI was defined as the revascularization failure with desert foot (absence of any artery below-the-ankle) or partial desert foot (absence of a wound-related artery with TcPO2 < 30 mmHg) at the final post-procedural angiogram. After one year of follow-up, the rate of major amputation was evaluated such as clinical, wound, and vascular features of amputees in comparison to not amputees. In addition, the factors influencing the risk of major amputation were analyzed.

Sixty-four patients were included. The mean age was 73.8 ± 5.8 years, 75% were male, and all of them had type 2 diabetes. At one year of follow-up, major amputation was documented in 12.5% of patients. Amputees had a higher rate of desert foot (vs. partial desert foot) (100% vs. 25%, p < 0.0001), higher post-procedural pain (5.7 ± 1.9 vs. 2.2 ± 1.3, p < 0.0001), lower TcPO2 after PB-MNCs therapy (30 ± 8 vs. 43 ± 8 mmHg, p = 0.0001), and more cases of heel ulcers (75% vs. 21.4%, p = 0.002). Independent predictors of major amputation resulted the presence of desert foot, persistence of post-procedural pain, heel involvement with multiple ulcers, and inability to stand or walk without assistance.

PB-MNCs therapy resulted less effective in patients with complete desert foot, persistence of paint after therapy, heel involvement in persons with multiple ulcers, and impaired walking.

This prospective cohort study systematically analyzed the demographic profile, clinical characteristics, spectrum of microorganisms, and antimicrobial resistance pattern in 248 patients with diabetic foot ulcer (DFU) over 2.7 years. Most patients were male (75.4%) and had a mean age of 56.1 years, and high comorbidity rates (81% neuropathy, 77% retinopathy, and 67.7% hypertension). A combined 439 bacterial isolates were obtained, with the dominance of Gram-negative pathogens, including Escherichia coli (16.6%) and Pseudomonas aeruginosa (15.3%). Staphylococcus aureus was also the dominant Gram-positive pathogen (12.8%). Polymicrobial infections were found in 43.1% of cases, and 71% of strains were biofilm-producing. The prevalence of multidrug-resistant (MDR) was alarmingly high (67%), particularly among Escherichia coli (97.3%), Staphylococcus aureus (83.9%), and Proteus mirabilis (90.5%). MDR infections were associated with tobacco use, biofilm formation, polymicrobial infection, and clinical complications. In specific, seven bacterial types, Pseudomonas aeruginosa, Staphylococcus aureus, Providencia rettgeri, Enterococcus faecalis, Enterobacter cloacae, Pseudomonas flourescens, and Staphylococcus epidermidis, as described, were statistically associated with amputation. Beta-lactams (ampicillin, piperacillin) showed 100% resistance. Cephalosporins (ceftazidime, ceftriaxone, cefotaxime, cefepime) had resistance rates ranging from 25 to 96%. Amoxicillin-clavulanic acid showed 30 to 92.3% resistance, while piperacillin-tazobactam ranged from 7.7 to 71.4% resistance. Out of 338 Gram-negative isolates, 105 (31.1%) were ESBL producers, and molecular characterization shows blaCTX-M as the most predominant, 40 (38.1%), followed by blaSHV 20 (19.0%), and blaTEM 7 (6.7%) isolates. Methicillin and vancomycin resistance were common among Gram-positive isolates, particularly Methicillin-resistant Staphylococcus aureus (MRSA) (51.8%) and Vancomycin-resistant Enterococci (VRE) (33.3%). Despite widespread resistance, antibacterial drugs such as colistin (100%), polymyxin B (100%), linezolid (100%), and vancomycin (100%) retained efficacy. These data emphasize the significant burden of MDR infections in DFUs and emphasize the urgent actions needed for aggressive antimicrobial stewardship, early infection control, and personalized treatment approaches to prevent amputation and enhance patient outcomes.

Diabetic foot infections (DFIs), predominantly caused by Staphylococcus aureus, pose a significant healthcare challenge with severe consequences, including amputation. Phage therapy, which utilizes bacteriophages to specifically target bacterial pathogens, has emerged as a promising alternative to conventional antibiotic treatments. This review evaluates the efficacy of phage therapy as a complementary treatment for DFIs caused by S. aureus, synthesizing evidence from preclinical and clinical studies while addressing the limitations and challenges associated with current research. The analysis highlights promising results from diabetic animal models, demonstrating effective bacterial load reduction and improved wound healing. Clinical case reports and series further underline significant improvements in infection management and ulcer healing, with no major adverse effects reported. Ongoing clinical trials are also discussed, offering insights into the study parameters evaluating phage therapy potential efficacy and safety for S. aureus-related DFIs. While the collected data highlight the potential of phage therapy as a valuable complement to traditional antibiotic treatments, particularly in managing antibiotic-resistant infections, further research is essential to address existing limitations, including gaps in long-term efficacy data and challenges in standardization. With continued investigation, phage therapy holds significant potential to alleviate the healthcare burden of DFIs and improve patient outcomes.

Background: Diabetic foot ulcers (DFUs) remain a major complication of diabetes, characterized by impaired wound healing, high infection risk, and an increased likelihood of limb amputation. Platelet-rich plasma (PRP) has emerged as a promising adjunctive therapy due to its regenerative properties, promoting angiogenesis, modulating inflammation, and accelerating tissue repair. Methods: This literature review explores the current evidence regarding the use of PRP in the management of DFUs. It was conducted using the PubMed database to evaluate the efficacy of PRP in DFUs. The search was restricted to studies published in the last 10 years, including randomized controlled trials, meta-analyses, and systematic reviews. The inclusion criteria focused on studies assessing PRP as a standalone treatment or in combination with other wound care strategies, evaluating key clinical outcomes such as wound healing rates, infection control, tissue regeneration, and amputation prevention. Results: A total of 35 studies met the inclusion criteria, including 11 meta-analyses, 15 review articles, and 9 clinical trials. PRP demonstrated potential benefits in accelerating wound healing, reducing inflammation, and promoting granulation tissue formation. Additionally, PRP combined with negative-pressure wound therapy (NPWT) showed superior outcomes in reducing amputation rates. However, findings varied based on patient characteristics, PRP preparation techniques, and treatment protocols. Conclusions: PRP represents a valuable adjunct in DFU management, contributing to improved healing outcomes and reduced complications. However, the lack of standardized protocols and variability in clinical results highlight the need for further large-scale, multicenter studies to establish its definitive role in diabetic wound care.

To evaluate the association between presenting estimated glomerular filtration rate (eGFR) and clinical outcomes in patients hospitalized with diabetic foot infections. This retrospective cohort study included 344 patients with moderate to severe diabetic foot infections. Patients were categorized into three groups based on presenting estimated eGFR: eGFR ≥60 (eGFR >60 mL/min), eGFR 30-60 (eGFR 30-60 mL/min) and eGFR <30 (eGFR <30 mL/min). Outcomes assessed included wound healing, time to heal, re-infection, amputation, mortality and re-hospitalization for infection. Compared with patients with eGFR <30, patients with eGFR ≥60 had significantly lower rates of retinopathy, peripheral arterial disease and use of beta blockers or calcium channel blockers. Glycated haemoglobin levels were inversely related to eGFR, decreasing as eGFR severity increased. Haemoglobin levels were significantly lower, and inflammatory markers (ESR and CRP) were significantly higher in patients with eGFR <30. There were no significant differences among eGFR groups in rates of wound healing, time to heal, re-infection or amputation. However, mortality increased with decreasing eGFR (1.9% in eGFR ≥60 vs. 3.2% in eGFR 30-60 vs. 8.1% in eGFR <30; p = 0.04). Similarly, re-hospitalization for infection at a different site also increased with decreasing eGFR (20.5% in eGFR ≥60 vs. 28.1% in eGFR 30-60 vs. 48.4% in eGFR <30; p < 0.01). In diabetic foot infections, presenting eGFR severity did not affect rates of wound healing, time to heal, re-infection or amputation. However, decreasing eGFR was associated with increased mortality and re-hospitalization for infection at a different site. In this study, presenting eGFR was not a predictive value for wound healing or time until healing, however was associated with rehospitalization and overall mortality this diabetic foot population.

Background: Diabetic wound is one of the most common diabetic chronic complications. Effective treatments of diabetic wound remain limited. Here, we explored the effects of basic fibroblast growth factor (bFGF)-acellular dermal matrix (ADM) hydrogel on the diabetic wound. Methods: The bFGF-ADM hydrogel was manufactured by mixing 180 µL ADM hydrogel and 20 µL bFGF aqueous solution (10 mg/mL). The morphology of ADM hydrogel and bFGF-ADM hydrogel was observed under scanning electron microscope. The release property of bFGF-ADM hydrogel was determined by ELISA. CCK-8 assay was utilized to estimate the cell viability of mouse skin fibroblasts. The diabetes mellitus (DM) model was established in rats. The four wounds on the back of each DM rat were treated with the ADM hydrogel, bFGF-ADM hydrogel, bFGF aqueous solution and no solution (control), respectively. The wound healing rate of each rat was estimated. The traumatized skin tissue of each rat was observed by H&E staining and Sirius red staining. Results: The bFGF-ADM hydrogel displayed an interconnected pore structure and bFGF was gradually released from the bFGF-ADM hydrogel over time. The bFGF-ADM hydrogel could enhance the cell viability of skin fibroblasts and promote the wound healing rate, the re-epithelialization of wound and increase the collagen fiber content of dermis. And the bFGF-ADM hydrogel exhibited better therapeutic effects of diabetic wound than either bFGF or ADM alone. Conclusions: Our study revealed that the bFGF-ADM hydrogel could promote diabetic wound healing.

Ten percent of adults in the United States have a diagnosis of diabetes and up to a third of these individuals will develop a diabetic foot ulcer (DFU) in their lifetime. Of those who develop a DFU, a fifth will ultimately require amputation with a mortality rate of up to 70% within five years. The human suffering, economic burden, and disproportionate impact of diabetes on communities of color has led to increasing interest in the use of computer vision (CV) and machine learning (ML) techniques to aid the detection, characterization, monitoring, and even prediction of DFUs. Remote monitoring and automated classification are expected to revolutionize wound care by allowing patients to self-monitor their wound pathology, assist in the remote triaging of patients by clinicians, and allow for more immediate interventions when necessary. This scoping review provides an overview of applicable CV and ML techniques. This includes automated CV methods developed for remote assessment of wound photographs, as well as predictive ML algorithms that leverage heterogeneous data streams. We discuss the benefits of such applications and the role they may play in diabetic foot care moving forward. We highlight both the need for, and possibilities of, computational sensing systems to improve diabetic foot care and bring greater knowledge to patients in need.

This study examines the relationship between the TyG index and the risk of sudden cardiac death (SCD) in the patients with diabetic foot ulcer (DFU).

688 type 2 diabetes mellitus (T2DM) inpatients with DFU between January 2010 and December 2023 was included in this retrospective study. The 1:1 propensity score matching (PSM) method was applied. The relationship between TyG index and SCD risk was analyzed using the Kaplan-Meier (K-M) survival curve analysis, multivariate Cox proportional hazard regression model, Restricted cubic spline (RCS) model analysis and subgroup analyses.

Over a median follow-up period of 61 months, 38 cases of SCD were recorded. After PSM, 71 pairs of score-matched patients according to TyG index were generated. K-M survival curves revealed higher SCD rates in patients with TyG index ≥9.65. The Cox proportional hazard model, independently associated with the risk of SCD (HR: 75.98; 95 % CI: 9.16 ∼ 630.40; P < 0.001). RCS model showed that SCD risk was non-linearly correlated with gradual increases in TyG index levels. Stratified analyses indicated a consistent relationship between increasing TyG index and SCD risk across all subgroups.

Elevated TyG index independently confers an increased risk for SCD in individuals with DFU.

Diabetic foot osteomyelitis (DFO) is associated with a considerably high risk of incident major amputations, disability and mortality. To assess the effects of a local antibiotic delivery system on the incidence of post-surgical infective complications in patients with DFO.

This is a double-blind, placebo-controlled, parallel series, randomized controlled trial (RCT) aimed at verifying the efficacy and safety of a local calcium-sulphate bio-absorbable antibiotic delivery (either with tobramycin or vancomycin) in patients with DFO treated with surgical procedures. The trial enrolled adult patients with diabetes and Texas 3 grade ulcers complicated by osteomyelitis and accompanied by deep tissues infection. The primary end-point was the percentage of infective complications (composite end-point of dehiscence, infection, DFO recurrence and new DFO in adjacent sites) at 12 weeks.

The study was prematurely terminated after the completion of the first 20 cases, because of the significant superiority of the active treatment arm. After 12 weeks of treatment, five of 20 wounds (25%) achieved the primary composite end-point. All post-surgical infective complications occurred in the placebo group, with a significant between-group difference (unadjusted p = 0.010). No between-group differences in overall costs were observed.

This is the first RCT in patients with DFO showing that the use of antibiotic-impregnated calcium-sulphate granules is economically sustainable and has the potential of improving the prognosis of DFO.

Diabetes mellitus is a global public health concern, with diabetic foot infections (DFIs) being common clinical complications among affected patients. Bacterial isolates resistant to commonly used antimicrobial drugs are becoming more prevalent in DFIs. Some research suggests that platelet-rich plasma (PRP) may inhibit bacterial growth, making it a promising biological therapy. Therefore, an in vitro experimental study was conducted on 53 multidrug-resistant (MDR) bacterial strains isolated from DFIs. The isolates were methicillin-resistant Staphylococcus aureus (MRSA), MDR Klebsiella pneumoniae, and MDR Pseudomonas aeruginosa. The antibacterial activity of PRP was assessed using Kirby-Bauer disk diffusion method, broth microdilution method, checkerboard synergy testing, and time-kill assay. The time-kill assay demonstrated that PRP's antibacterial efficacy peaked during the second hour of incubation for MRSA and Pseudomonas aeruginosa, but peaked at the first hour for Klebsiella pneumoniae. However, the PPR's efficiency against all isolates decreased after the peak point, with no antibacterial activity observed at the 24th h of incubation. Additionally, biofilm inhibition and eradication assays revealed that PRP has no effect on biofilm formation. As a result, PRP has the ability to inhibit bacterial growth, although this effect is transient and depends on the bacterial strain.

Peripheral arterial disease (PAD) is characterized by atherosclerotic arterial occlusive disease of the lower extremities and is associated with an increased risk of major adverse cardiovascular events (MACE) in addition to disabling clinical sequelae, including intermittent claudication and chronic limb-threatening ischemia (CLTI). Given the growing burden of disease, knowledge of modern practices to prevent MACE and major adverse limb events (MALE) is essential. This review article examines evidence for medical management of PAD and its associated risk factors, as well as wound prevention and care.

A thorough review of the literature was performed, with attention to evidence for the management of modifiable atherosclerotic risk factors, claudication symptoms, wound prevention, and wound care.

Contemporary management of PAD requires a multi-faceted approach to care, with medical optimization of smoking, hypertension, hyperlipidemia, and diabetes mellitus. The use of supervised exercise therapy for intermittent claudication is highlighted. The anatomic disease patterns of smoking and diabetes mellitus are discussed further, and best practices for diabetic foot ulcer prevention, including offloading footwear, are described. Quality wound care is essential in this patient population and involves strategic use of debridement, wound-healing adjuncts, and skin substitutes, when appropriate.

The objective of medical management of PAD is to reduce the risk of MACE and MALE. Atherosclerotic risk factor optimization, appropriate wound care, and management of diabetic foot ulcers, foot infections, gangrene, and chronic, non-healing wounds are critical components of PAD care. Interdisciplinary care is essential to coordinate care, leverage expertise, and improve outcomes.

Prolonged length of stay (LOS) in the emergency department (ED) and lack of post-ED follow-up pose a risk of worsening infection and amputation among patients with diabetic foot complications.

Excessive ED LOS posed a risk of delayed foot care, and triage providers underutilized post-ED telehealth referrals.

A graphic icon on the ED dashboard, nurse-initiated order set, and staff education were implemented.

A pre-/postimplementation design was used. Outcomes included usage of the graphic icon and order set, ED LOS, and telehealth referrals.

Use of the graphic icon and order sets significantly increased ( P < .001). The rate of telehealth referrals upon discharge also increased but was not significant ( P = .086). Interestingly, LOS increased after the intervention.

Using the graphic icon and order set can streamline patient referral to telehealth care. Various factors lead to an extended LOS.

Due to limited data on the epidemiology of diabetic foot ulcers (DFU) in Germany, especially for those infected, the study determined the prevalence and incidence of DFU and the associated medical burden. Anonymised claims data of 3.3 million insured lives were sourced from a statutory health insurance fund. Patients with DFU between 04/01/2016 and 12/31/2019 were selected (n = 7764) and divided into patients with/without infection/with prophylactic use of antibiotics. Outcome variables were described categorically. Two-sided t-tests and chi-squared tests (p < 0.05) were performed. The prevalence and incidence in patients with DFU was 4.6% and 2.1%, respectively. The mean Charlson Comorbidity Index was 7.9, significantly higher in those infected than in those uninfected (8.1% vs. 7.2%, p < 0.0001). Amputations occurred significantly more often in DFU patients with infection than in those without (minor 25.4% vs. 3.0%, p < 0.0001; major 6.7% vs. 1.2%, p < 0.0001). The 5-year mortality rate was significantly higher in patients with infection than in those without (64.0% vs. 51.3%, p < 0.0001). The occurrence of comorbidities and complications associated with DFU, in particular the high overall medical burden and mortality rate-especially in DFU patients with infections-underscores the importance of prevention and early, appropriate treatment.

Diabetic foot (DF) is a major public health concern. As evident from numerous previous studies, supervision of DF ulcer (DFU) is crucial, and a specific quality check-up is needed. Patients should be educated about glycaemic management, DFUs, foot lesions, proper care for injuries, diet, and surgery. Certain reasonably priced treatments, such as hyperbaric oxygen and vacuum-assisted closure therapy, are also available for DFUs, along with modern wound care products and techniques. Nonetheless, DF care (cleaning, applying antimicrobial cream when wounded, and foot reflexology), blood glucose monitoring to control diabetes, and monthly or quarterly examinations in individuals with diabetes are effective in managing DFUs. Between 50% and 80% of DF infections are preventable. Regardless of the intensity of the lesion, it needs to be treated carefully and checked daily during infection. Tissue regeneration can be aided by cleaning, dressing, and application of topical medicines. The choice of shoes is also important because it affects blood circulation and nerve impulses. In general, regular check-ups, monitoring of the patient's condition, measuring blood glucose levels, and providing frequent guidance regarding DFU care are crucial. Finally, this important clinical problem requires involvement of multiple professionals to properly manage it.

Diabetic foot infections (DFIs) and diabetic foot osteomyelitis (DFO) are common and serious complications in patients with diabetes, often leading to severe morbidity (including amputation) and even mortality. Professional footcare, prompt diagnosis and appropriate treatment are crucial to preventing limb loss and improving outcomes in infections.

This narrative review addresses the management of all DFIs, including the approach to clinical evaluation, appropriate diagnostic methods, and optimal therapeutic strategies. We specifically address key areas in antibiotic therapy, and surgical interventions and techniques. Based on our literature review and extensive, multidisciplinary experience, we developed a novel treatment flowchart specifically for the management of DFO.

Managing DFIs, including DFO, requires a multidisciplinary approach tailored to each patient's clinical presentation. While antibiotics, surgery, and wound care each play a crucial role, the decision-making process should always consider the infection's severity and chronicity. Our proposed flowchart for DFO management emphasizes the importance of logically-sequenced, easy to apply and tailored interventions to prevent unnecessary amputations and improve outcomes. Further research is needed to further refine this flowchart in clinical practice and demonstrate its effectiveness.

Little information exists about diabetic foot infections (DFIs) in older patients. We hypothesize that older patients with DFIs have different clinical features and worse outcomes than younger patients. We conducted a prospective observational study consisting of a cohort of patients with diabetes and moderate to severe DFIs. Patients included in the cohort were dichotomized into two groups using percentile 75 (P75) of age as the cut-off value. Patients aged > P75 presented with more comorbidities and foot-related complications, a higher rate of peripheral arterial disease (PAD), worse renal function (higher values of blood urea nitrogen and creatinine, and lower values of estimated glomerular filtration rate), and lower values of HbA1c compared with younger patients. Infection severity, microbiological features, and inflammatory markers were similar in both groups. In the multivariate analysis, minor amputations were associated with age > P75 (OR = 2.8, 95% CI 1.3-5.9, p <0.01), necrosis (OR = 4.2, 95% CI 1.8-10.1, p < 0.01), and CRP values (OR = 1.045, 95% CI 1.018-1.073, p < 0.01). Major amputations were associated with a history of amputation (OR = 4.7, 95% CI 1.3-16.7, p = 0.01), PAD (OR = 4.3, 95% CI 1.2-14.6, p = 0.01), and albumin values (OR = 0.344, 95% CI 0.130-0.913, p = 0.03). In conclusion, limb salvage can be achieved in older patients with diabetes-related foot infections at the same rate as in younger patients, despite the fact that they have more comorbidities and foot-related complications, a higher rate of PAD, and worse renal function.

Osteomyelitis is characterized by inflammation of the bone tissue, typically caused by microorganisms such as bacteria. It can be challenging to treat and may lead to unnecessary antibiotic therapies. Prompt identification of osteomyelitis and implementation of effective treatments are necessary to eradicate this infection. This article discusses the pathophysiology, clinical presentation, diagnosis, and nursing management of osteomyelitis, focusing on native bone infection.

This review examines the challenges posed by Diabetic Foot Infections (DFIs), focusing on the impact of neuropathy, peripheral arterial disease, immunopathy, and the polymicrobial nature of these infections. The aim is to explore the factors contributing to antimicrobial resistance and assess the potential of novel antimicrobial treatments and drug delivery systems in improving patient outcomes.

A comprehensive analysis of existing literature on DFIs was conducted, highlighting the multifactorial pathogenesis and polymicrobial composition of these infections. The review delves into the rise of antimicrobial resistance due to the overuse of antimicrobials, biofilm formation, and microbial genetic adaptability. Additionally, it considers glycemic control, patient adherence, and recurrence rates as contributing factors to treatment failure. Emerging therapies, including new antimicrobial classes and innovative drug delivery systems, were evaluated for their potential efficacy.

DFIs present unique treatment challenges, with high rates of antimicrobial resistance and poor response to standard therapies. Biofilm formation and the genetic adaptability of pathogens worsen resistance, complicating treatment. Current antimicrobial therapies are further hindered by poor glycemic control and patient adherence, leading to recurrent infections. Novel antimicrobial classes and innovative delivery systems show promise in addressing these challenges by offering more targeted, effective treatments. These new approaches aim to reduce resistance and improve treatment outcomes.

DFIs remain a clinical challenge due to their multifactorial nature and antimicrobial resistance. The development of novel antimicrobials and drug delivery systems is crucial to improving patient outcomes and combating resistance. Future research should focus on enhancing treatment efficacy, reducing resistance, and addressing patient adherence to reduce the burden of DFIs.

The aim of this study was to evaluate the effect on wound healing of intralesional epidermal growth factor (iEGF) (Heberprot-p; Hasbiotech, Cuba) and autologous adipose-derived tissue stromal vascular fraction (AD-tSVF) applied in the closure of tissue defects.

The patients included in the study were separated into three approximately equal groups: Group 1 with iEGF+AD-tSVF applied; Group 2 with iEGF only applied; and Group 3 with conventional wound care products applied. Granulation tissue was taken from the wound bed before the application of iEGF and AD-tSVF and at intervals thereafter for flow cytometry analysis.

Group 1 included 11 patients; Group 2 included 10 patients; and Group 3 included 10 patients. The time to re-epithelialisation was determined as 187.60±68.78 days in Group 3 patients compared with Group 1 (72.27±10.33 days) and Group 2 (70.50±18.02 days) (p<0.001). Following the application of iEGF to the wound bed, an increase was observed in M2 macrophage (CD209+), and M1 macrophage (CD38+) levels. The (CD34+) stem cells obtained from the granulation tissue after the application of AD-tSVF were determined to still be statistically significantly increased in the wound bed on the 21st day.

The results of this study demonstrated that the application of iEGF and iEGF+ AD-tSVF significantly shortened the wound healing period compared with conventional methods. AD-tSVF stands as an effective option, especially in the patient group with halted or delayed wound healing despite the application of iEGF. Moreover, the significant increase (p<0.001) in the level of M2 macrophages (CD209+), M1 macrophages (CD38+) and stem cells (CD34+) provided by this treatment modality showed that it contributed to wound healing at the cellular level.

We aim to identify the factors associated with the failure of amputation of one to three toes (index toe amputation) in patients with diabetes and foot infection. We conducted a retrospective cohort of 175 patients with diabetes who were hospitalized for moderate to severe foot infection and underwent amputation of one to three toes. A Poisson regression model was used to determine the prevalence ratio (PR) as a measure of association. The mean age was 63.3 ± 11.4 years. Fifty-three patients presented failure after undergoing toe amputation (30.3%). Multivariate analysis, adjusted for age and sex, showed the following significant variables: severe infection (PR: 1.78; 95% confidence interval [CI]: 1.14-2.78; P = 0.011), infection by Escherichia coli (PR: 2.21; 95% CI: 1.42-3.43; P < 0.001), infection by Pseudomonas aeruginosa (PR: 2.11; 95% CI: 1.29-3.43; P = 0.003) and prothrombin time (PR: 1.13; 95% CI: 1.05-1.21; P = 0.001), obesity (PR: 0.58; 95% CI: 0.37-0.93; P = 0.024), and haemoglobin value (PR: 0.92; 95% CI: 0.86-0.99; P = 0.023). About one-third of patients who underwent amputation of one to three toes for diabetic foot infection presented a failure and required a more proximal surgery. Severe infections, isolation of Pseudomonas aeruginosa and Escherichia coli, and prolonged prothrombin time were associated with a higher prevalence of failure. However, obesity and an elevated haemoglobin level were associated with a lower prevalence of failure.

Diabetic foot ulcer (DFU) inpatients admitted with non-ulcer complaints constitute a neglected group that might suffer from more non-standard treatments. This study intends to describe their clinical characteristics, and clarify the problems existing in the DFU management process.

In this retrospective study, admission complaints were determined by combining the final diagnosis and clinical documentation, and were categorized as: ulcer-related or non-ulcer complaints.

A total of 264 DFU inpatients were included in the final analysis, of which, 80 (30.3%) were admitted with non-ulcer complaints. A total of 82.5% of the DFU inpatients with non-ulcer complaints were admitted to departments without DF specialists. IWGDF/IDSA grade, cerebrovascular diseases, chronic kidney disease, infection in other parts, glycosylated hemoglobin A1c and the source of hospitalization expenses were the independent influencing factors for admission with non-ulcer complaints (all P < 0.05). Before admission, only 11.3% of the patients with non-ulcer complaints had ever been treated by a DF specialist and/or in a clinical setting with DF specialists. After admission, 25.0% of the DFU inpatients with non-ulcer complaints did not receive any local wound care, and only 7.6% of the patients admitted to the departments without DF specialists obtained a referral.

Approximately one-third of inpatients with DFU are admitted with non-ulcer complaints and most of them are admitted to departments without DF specialists. Inpatients with non-ulcer complaints have milder wounds but more severe and greater comorbidities and worse organ function. These patients do not receive standardized management for DFU either before or after admission. Targeted measures are needed to improve this situation.

Diabetic foot ulcers (DFU) are a significant complication of diabetes, with huge implications on patient morbidity and healthcare costs. The objective of this meta-analysis was to evaluate the impacts of stem cells from different sources on wound healing rate in DFU patients.

We systematically retrieved records via key databases PubMed, Cochrane Library, Web of Science, Embase, China National Knowledge Infrastructure (CNKI) and Wanfang from the inception to October 2024. The Stata 16.0 (Stata Corp, TX) software was used to perform the meta-analysis. Risk of bias in all included studies was evaluated by Cochrane Risk of Bias version 2.

A total of 24 studies involving 1,321 patients were included. There was an increased likelihood of wound healing with peripheral blood-derived stem cells, the most effective cells (odds ratios (OR) = 7.31, 95% CI: 2.90-18.47), followed by adipose-derived stem cells (OR = 5.23, 95% CI: 2.76-9.90), umbilical cord-derived stem cells (OR = 4.94, 95% CI: 0.61-40.03), bone-derived stem cells (OR = 4.36, 95% CI: 2.43-7.85) and other sources stem cells (OR = 3.16, 95% CI: 1.83-5.45). Nevertheless, only umbilical cord-derived stem cells showed statistical significance (p < 0.05). The heterogeneity ranged from non-existent in the adipose and peripheral blood groups (I2 = 0.00%) to moderate in the bone groups (I2 = 26.31%) and other groups (I2 = 30.62%), and substantial in the umbilical cord groups (I2 = 88.37%). Asymmetrical funnel plots pointed to publication bias, but the trim-and-fill method to correct for this brought the effect estimates even lower: based on the pooled OR, corrected OR was 3.40 (95% CI 2.39-4.84). Stem cell therapy was also associated with improvements in several secondary outcomes, suggesting its potential to influence the progression of DFU.

Our study suggested that stem cells from different sources showed potential in promoting wound healing in DFU, although with some variation in effectiveness. Despite some publication bias and moderate heterogeneity, the overall therapeutic effect remained positive. These findings indicated that stem cell therapy might influence the progression of DFU.

Our objective was to compare clinical outcomes in diabetic foot ulcers (DFU) treated with AmnioExcel® applied weekly (AMX1) or biweekly (AMX2) over a 12-week evaluation period. This randomized clinical trial evaluated 40 people with UT 1A and 1D DFUs >30 days but less than 6 months duration and age >21 years. We excluded patients with untreated osteomyelitis, gangrene, widespread malignancy, or active substance abuse. Patients received amniotic tissue either once a week or every other week. We used a 3D measurement device (inSight, eKare, Fairfax, Virginia)". There was no difference in the incidence of healing (AMX1 30.0% vs AMX2 50.0%, p = 0.20), time to heal (69.3 ± 30.3 vs 45.8 ± 25.6 days, p = 0.15), or incidence of infection (AMX1 35.0% vs AMX2 25.0%, p = 0.49). The mean wound area reduction was 0.18 ± 0.48 cm2 per week for AMX1 and 0.15 ± 0.63 cm2 week for AMX2 (p = 0.42). When we compared wound healing trajectories in healers and non-healers. There were no differences in the mean wound area reduction for healers (0.26 ± 0.40 cm2 per week) and non-healers (0.14 ± 0.52 cm2 per week, p = 0.20). Our results suggested there is no difference in the incidence of healing, time to heal or incidence of infection based on weekly or biweekly application of amniotic tissue.

Background: Diabetic foot ulcers (DFUs) represent severe complications in diabetic patients, often leading to chronic infections and potentially resulting in nontraumatic lower-limb amputations. The increasing incidence of multidrug-resistant (MDR) bacteria in DFUs complicates treatment strategies and worsens patient prognosis. Among these pathogens, carbapenemase-producing pathogens have emerged as particularly concerning owing to their resistance to β-lactam antibiotics, including carbapenems. Methods: This study evaluated the prevalence of MDR bacteria, specifically carbapenemase-producing pathogens, in DFU infections. A total of 200 clinical isolates from DFU patients were analyzed via phenotypic assays, including the modified Hodge test (MHT) and the Carba NP test, alongside molecular techniques to detect carbapenemase-encoding genes (blaKPC, blaNDM, blaVIM, blaIMP, and blaOXA-48). Results: Among the isolates, 51.7% were confirmed to be carbapenemase producers. The key identified pathogens included Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii, and Escherichia coli. The most commonly detected carbapenemase genes were blaKPC (27.6%) and blaNDM (24.1%). Carbapenemase-producing isolates presented high resistance to β-lactam antibiotics, whereas non-carbapenemase-producing isolates presented resistance through mechanisms such as porin loss and efflux pumps. Conclusions: The findings of this study highlight the significant burden of MDR infections, particularly carbapenemase-producing organisms, in DFUs. MDR infections were strongly associated with critical clinical parameters, including pyrexia (p = 0.017), recent antibiotic use (p = 0.003), and the severity of infections. Notably, the need for minor amputations was much higher in MDR cases (p < 0.001), as was the need for major amputations (p < 0.001). MDR infections were also strongly associated with polymicrobial infections (p < 0.001). Furthermore, Wagner ulcer grade ≥II was more common in MDR cases (p = 0.002). These results emphasize the urgent need for enhanced microbiological surveillance and the development of tailored antimicrobial strategies to combat MDR pathogens effectively. Given the high prevalence of carbapenem resistance, there is an immediate need to explore novel therapeutic options to improve clinical outcomes for diabetic patients with DFUs.

Slough is not currently a recommended microbiology culture specimen. The aim of our work is to analyse the concordance of results between slough and swab samples for cultures. A single-centre, retrospective, cross-sectional study involving patients (n = 131) with hard to heal wounds was conducted from October 2022 to October 2023. Pairs of slough and swab samples were collected for microbiological analysis and subdivided depending on whether a relatively clean wound bed was obtained. Swab samples were collected using the Levine and deep pus methods, Cohen's κ coefficients calculated to evaluate concordance, and microbiological agreement analysed. Gram-stain results did not differ significantly between slough and swab samples (𝜒2 = 329.287, p = 0.688; concordance, κ = 0.879, p < 0.001); microbiological agreement was 90.1%. Samples from 87 patients with relatively clean wound beds generated excellent concordance between slough and Levine technique (κ = 0.867, p < 0.001; microbiological agreement, 89.7%). In 44 patients with slough and deep pus swab where a relatively clean wound bed could not be obtained, Gram-stain also demonstrated excellent concordance (κ = 0.898, p < 0.001; microbiology agreement, 90.9%). Our data provide evidence that slough is a reliable wound specimen from hard to heal wounds for microbiology culture.

Our objective was to evaluate risk factors for re-infection in patients after treatment for diabetic foot osteomyelitis (OM). We used pooled patient level data from two RTCs that evaluated patients with diabetic foot infections. We evaluated 171 patients with OM. OM was confirmed with bone culture or histopathology. Data from the 12-month follow-up were used to determine clinical outcomes. Re-infection occurred in 47 (27.5%) patients. Risk factors for re-infection were Toe Brachial Index <0.40 (25.7% vs. 9.8%, p = 0.02), skin perfusion pressure <40 mmHg (6.3% vs. 5.9%, p = 0.04), wound healing (55.3% vs. 75.0%, p = 0.01), time to heal (156.0, 69.5-365 vs. 91.5, 38.8-365, p = 0.001), and history of MI (14.9% vs. 3.2%, p = 0.005). During 12-month follow-up, patients with re-infections were 198.8 times more likely to require a foot related hospitalisation (81.8% vs. 0.0%, p = 0.001), 10.4 times more likely have an all-cause hospitalisation (70.2% vs. 18.5%, p = 0.001) and 9.4 times more likely to need an amputation (36.2% vs. 5.6%, p = 0.001). Patients with re-infection had a significantly longer median length of hospitalisation (20.0, 13.5-34.5 vs. 14.0, 10.0-22.0, p = 0.003) and median length of antibiotic duration (55.0, 35.0-87.0 vs. 46.0, 22.8-68.0, p = 0.03). Patients with re-infection are less likely to heal and have more foot-related hospitalizations and amputations.

Osteomyelitis complicates 20% of patients with infected diabetic foot ulcers. In this study, 2 strategies for treating pedal osteomyelitis were compared in a pilot study. This was a retrospective, non-randomized, single center 2 arm cohort study, conducted between 2020 and 2022 involving 53 patients at a tertiary limb salvage unit. All patients were managed with debridement and proximal bone biopsy. Group A was treated with systemic antibiotics for up to 6 weeks. Group B had vancomycin or gentamycin eluting bone void filler implanted into the diseased bone medullary cavity(s) and 1 week of oral antibiotics. Patients were followed independently for the primary endpoint of osteomyelitis treatment failure and secondary endpoints of amputation free survival, wound healing, minor amputation, and treatment-limiting side-effects. Survival analysis demonstrated no significant difference in treatment failure (p = .35) or amputation free survival (p = .46). Limb salvage rates were 88% in Group A and 89% in Group B. Wounds healed in 85% in Group A and 89% in Group B. Minor amputations occurred in 21% in Group A and 11% in Group B. Treatment limiting side effects occurred in 6% in Group A and were absent in Group B. In conclusion, the use of antibiotic eluting bone void filler appeared safe without extended systemic antibiotics in this study. Group B had fewer intravenous lines, requirement for home nursing, and treatment limiting side effects. A larger randomized controlled trial examining longer term clinical and radiological efficacy, treatment costs and side effects is warranted.

Our objective was to assess the incidence, risk factors and clinical outcomes of dehiscence after foot surgery in diabetic patients. We used pooled patient-level data from two randomised clinical trials with 240 diabetic patients who required foot surgery for infections. Most patients (n = 180, 75.0%) had surgical wound closure. We defined dehisced surgical wounds (DSW) when the surgical site was not completely epithelialized with no drainage after sutures/staples were removed with a 2-week validation of healing. We evaluated the time to heal, re-infection, re-ulceration, hospital admissions and amputations. Moderate and severe infection was based on criteria of the International Working Group on the Diabetic Foot. We used χ2 and t-test and Mann-Whitney U for comparison of clinical events, with α of <0.05. DSW occurred in 137 (76.1%) patients. DSW patients were more likely to have hypertension (62.8% vs. 81.8%, p = 0.01), high ESR (59.1 ± 37.9 vs. 75.9 ± 37.6, p = 0.01), low toe brachial indices (0.8 ± 0.2) (0.7 ± 0.2, p = 0.005), toe brachial indices <0.6 (16.7% vs. 40.9%, p = 0.008), and low skin perfusion pressure measurements (dorsal medial 71.0 ± 29.4 vs. 59.3 ± 23.3, p = 0.01, and plantar medial 81.8 ± 24.9 vs. 72.2 ± 20.4, p = 0.02). During 12-month follow-up, DSW patients were 12.9 times more likely to have re-infection (0% vs. 12.4%, p = 0.02) and 6.8 times more likely to require amputation (2.3% vs. 13.9%, p = 0.04). The median healing time (28, 22.5-35.0 vs. 114.0, 69.0; 365, p = 0.001), and median length of hospitalisation were longer in DSW patients (12.0, 9.01-9.0 vs. 15.0, 11.0-24.0, p = 0.04). There was a high incidence of DSW, associated with poor clinical outcomes.

This study suggests that conservative surgery may improve reulceration-free survival in patients with diabetes-related forefoot osteomyelitis, compared to minor amputation. By excluding patients with prior surgeries, the analysis more accurately reflects the benefits of conservative surgery. These findings highlight the importance of preserving foot structure to maintain biomechanics and reduce reulceration risk.

Diabetic foot wounds and infections pose a significant and evolving challenge in diabetes care. Diabetic wound healing has become a major global concern for a very long time. Continuous research has been conducted to increase the healing process in diabetic ulcers to the rate of amputation. Wound healing is prolonged in diabetic patients due to various conditions, such as high glucose levels, neuropathy, poor blood circulation, and prolonged inflammation around the limbs, which causes the healing to be delayed compared to normal patients. Understanding the complexity of chronic foot wounds and the management and proper treatment would lead to a decrease in the risk of amputation. The medical team all over the world is constantly researching to lower the risk. This review paper offers a compelling journey through the multifaceted world of diabetic foot wounds and infections. It underscores the urgency of understanding classification, tackling multidrug resistance, and harnessing microbial insights to revolutionize the treatment and management of diabetic foot complications. Furthermore, it unveils state-of-the-art diagnostics, heralding a brighter future in the battle against this debilitating complication of diabetes.

To assess the effects of several adjuvant therapies (AT) commonly used in the treatment of diabetic foot ulcers (DFU). The present meta-analysis was designed to support the development of the Italian Guidelines for the Treatment of Diabetic Foot Syndrome.

A Medline and Embase search were performed up to May 20th, 2024 collecting all RCTs including diabetic patients or reporting subgroup analyses on diabetic patients with DFU comparing AT with placebo/standard of care (SoC), with a duration of at least 12 weeks. Prespecified endpoints were: ulcer healing (principal), time-to-healing, major and minor amputation, serious adverse events (SAE), and all-cause mortality. AT assessed were: growth factors (GF), Platelet-rich plasma and fibrin (PRP/F), skin substitutes (SS), negative pressure wound therapy (NPWT), and hyperbaric oxygen therapy (HBOT). Mantel-Haenzel Odds ratios and 95% confidence intervals (MH-OR, 95% CIs) were either calculated or extracted directly from the publications. Weighted mean differences and 95% CIs were calculated for continuous variables.

Fifty-one studies fulfilled all inclusion criteria (3, 5, 27, 8, and 8 with GF, PRP/F, SS, NPWT, and HBOT, respectively). Participants treated with any of the explored AT had a significantly higher ulcer healing rate (MH-OR ranging from 2.17 to 4.18) and shorter time-to-healing in comparison with SoC/placebo. Only PRP/F and HBOT showed a significantly lower risk of major amputation (MH-OR: 0.32(0.11;0,93; p = 0.04 and 0.28(0.10;0,79; p = 0.02, respectively), despite a higher risk of SAE. No other significant effects on the above-reported prespecified endpoints were observed. For the primary endpoint, the quality of evidence was rated as "high" for all the AT, except for NPWT ("moderate").

In conclusion, AT can actively promote wound healing and shorten time-to-healing in patients with DFU. HBOT and PRP/F also showed a reduction of the risk of major amputation, despite a higher rate of SAE.

The study is to investigate how residual osteomyelitis at conservative surgical resection margins affects the prognosis of diabetic toe osteomyelitis.

In this retrospective study, 67 participants with diabetic toe osteomyelitis who underwent conservative surgery were evaluated. The diagnosis of osteomyelitis was based on histopathology, and bone histopathology was done on the resection bone. After discharge, a 16-week follow-up was conducted, focusing on the wound healing time as the primary outcome. Cox regression analysis was employed as the primary method to analyse the risk factors that influence wound healing.

Among the 67 participants, 48 (71.6%) had positive bone margins, while 19 (28.4%) had negative bone margins. Participants with positive bone margins experienced an average healing time of 60.78 ± 18.50 days, whereas those with negative bone margins had an average healing time of 55.19 ± 14.60 days (p = 0.285). Bone margins (positive vs. negative) did not have an impact on wound healing (HR, 1.195 [95% CI, 0.668-2.136]; p = 0.549). Ankle-brachial index was identified as a factor influencing wound healing (HR, 5.399 [95% CI, 1.145-25.455]; p = 0.033). There was no statistical difference between the two groups in terms of wound healing rates (40 of 48 [83.3%] vs. 16 of 19 [84.2%], p = 0.93), inpatient days (19.48 ± 5.25 vs. 18.26 ± 4.79 days, p = 0.385) and duration of antibiotics (32.33 ± 5.64 vs. 30.53 ± 6.93 days, p = 0.272).

The residual osteomyelitis in diabetic toe osteomyelitis post-conservative surgery does not impact the wound healing.

The management of diabetic foot osteomyelitis (DFO) is complex. The targeted use of adjuvant local antibiotics, in the form of biocomposite bone void filler, in DFO, can enhance patient outcomes while minimising the adverse effects associated with systemic antibiotic therapy and its shortcomings.

We reviewed a series of 105 consecutive patients who underwent surgical management for diabetic foot osteomyelitis. In the NLAB group, (no adjuvant local antibiotic use), 49 patients, received the current standard of care treatment with no use of adjunctive local antibiotic therapy. In group LAB, (adjuvant use of local antibiotics), 56 patients received additional adjuvant local antibiotic therapy. Patient outcomes were compared between both groups.

Infection healing was demonstrated in 10 (20.41%) patients from group NLAB and 41 (73.21%) from group LAB (p < 0.0001). Persistence of infection with no evidence of wound healing, 6 months from surgery, was observed in 15 (30.61%) patients in group NLAB. Among the LAB group, only 4 (7.14%) patients demonstrated infection persistence (p = 0.00183). Reinfection was observed in 24 of 49 patients in group NLAB (49%) and in only 11 out of 56 patients in group LAB (20%) (p = 0.001466). 7 (6.67%) patients required major amputation with 6 (12.24%) belonging to group NLAB. Only 1 (1.78%) patient in group LAB underwent major amputation. A higher 5-year mortality rate was noted within patients in group NLAB, 27 (55.1%). The mortality rate in group LAB was (12.5%).

The adjuvant use of antibiotic loaded bio-composite bone void filler locally was associated with increased infection clearance rates regarding diabetic foot osteomyelitis when compared with the standard care of treatment while achieving lower rates of infection persistence and recurrence. It also has the potential to reduce amputation and mortality rates with further research.

Background: The optimal antimicrobial treatment duration for diabetes-related foot osteomyelitis (DFO) currently needs to be determined. We systematically reviewed the effects of short and long treatment durations on outcomes of DFO. Methods: We performed a systematic review searching Cochrane, CENTRAL, MEDLINE, Embase, and CINAHL Plus from inception up to 19 January 2024. Two independent reviewers screened the titles and abstracts of the studies. Studies comparing short (<6 weeks) and long (>6 weeks) treatment durations for DFO were included. The primary outcome was amputation; the secondary outcomes were remission, mortality, costs, quality of life, and adverse events. Risk of bias and GRADE were assessed. Results: We identified 2708 references, of which 2173 remained after removing duplicates. Two studies were included. Differences in methodology precluded a meta-analysis. The primary outcome, major amputation, was reported in one study, with a rate of 10% in both the intervention and comparison groups (p = 1.00), regardless of treatment duration. For the secondary outcome, remission rates, the first study reported 60% in the intervention group versus 70% in the comparison group (p = 0.50). In the second study, remission rates were 84% in the intervention group versus 78% in the comparison group (p = 0.55). Data for the outcomes mortality, costs, and quality of life were not available. Short treatment duration may lead to fewer adverse events. The risk of bias was assessed as low to moderate, and the level of evidence ranged from very low to moderate. Conclusions: Our findings suggest that for DFO, there is no difference between a shorter and more prolonged duration of antimicrobial treatment regarding amputation and remission, with potentially fewer adverse events with shorter treatment durations. However, the uncertainty stems from limited, heterogeneous studies and generally low-quality evidence marred by moderate biases, imprecision, and indirectness. More high-quality studies are needed to substantiate these findings.

The study aimed to evaluate the effectiveness of the use of sucrose octasulfate impregnated dressing (TLC-NOSF [Technology Lipido-Colloid-Nano-OligoSaccharide Factor]) in the management of persons with neuro-ischaemic heel diabetic foot ulcers (DFUs). Consecutive patients who referred for an active non-infected neuro-ischaemic heel DFU belonging to grade IC (superficial) or IIC (deep to tendons, muscle or capsule) according to Texas University Classification were included. All patients were managed by a pre-set limb salvage protocol in the respect of International guidelines and the TLC-NOSF dressing was used as primary and specific dressing. Patients were evaluated any 2 to 4 weeks until wound healing or different outcomes. Primary outcome was the rate of complete wound healing after 24 weeks of follow-up. The secondary outcomes assessed the healing time, the rate of wound regression, the re-ulceration in the case of complete healing and the safety. Thirty patients were included. The mean age was 67 ± 11 years, 17 (56.7%) were male, all of them were affected by type 2 diabetes with a mean duration of 18 ± 7 years. Twenty patients (66.7%) showed deep ulcers (grade 2 of Texas University Classification); the mean TcPO2 at the inclusion was 42 ± 7 mm Hg. Twenty-two patients (73.3%) healed by Week 24. The mean time of healing was 84 ± 32 days, 2 (6.7%) patients had ulcer relapse after healing, 28 (93.3%) had wound regression >50%, 2 (6.7%) had mild infection, 1 (3.3%) reported major amputation. No serious adverse events related to TLC-NOSF dressing or local reactions were reported. This current study showed the potential benefit of sucrose octasulfate for treating neuro-ischaemic heel DFUs in addition to the standard of care.

One of the most prominent challenges related to the management of diabetes is a diabetic foot ulcer (DFU). It has been noted that > 50% of ulcers become clinically infected in diabetic patients, and up to 15-25% of diabetic patients may acquire DFU in their lifetime. DFU treatment is complicated for immune-compromised individuals and has a low success rate. Therefore, diabetic foot care must begin as soon as possible to avoid negative outcomes such as significant social, psychological, and economic consequences, lower limb amputation, morbidity, and mortality. The information provided in this piece is crucial for assisting clinicians and patients regarding novel and cutting-edge treatments for DFU. Due to irrational recourse to antibiotics, etiological agents like bacteria and fungi are exhibiting multidrug resistance (MDR), making topical antibiotic treatments for wounds ineffective with the drugs we currently have. This review article aims to compile the various strategies presently in use for managing and treating DFUs. The piece covers topics like biofilm, diagnosis, drug resistance, multidisciplinary teamwork, debridement, dressings, offloading, negative pressure therapy, topical antibiotics, surgery, cell and gene therapy, and other cutting-edge therapies.

Background: Osteomyelitis is one of the most frequent infections of the diabetic foot, accounting for 20-70% of foot infections. The treatment of osteomyelitis continues to be debated, and the possibility of performing conservative surgery associated with targeted antibiotic treatment allows for reductions in the amount of bone removed, the resolution of osteomyelitis, and a reduction in the changes in the biomechanics of the foot. The objective of this study was to evaluate the outcomes of osteomyelitis treatment with a combination of antibiotic and surgical procedures based on a histopathological analysis of the infected bone and margins. Materials and Methods: We analyzed 25 diabetic patients with osteomyelitis. We treated each patient with empiric antibiotic treatment, surgical removal of the infected bone, and targeted antibiotic treatment. During the surgical procedure, we collected infected bone samples and margins for microbiological and histopathological analyses. Results: All the patients had type 2 diabetes, with a mean age of 71 ± 10 years. Antibiotic therapy was administered orally for an average duration of 21 ± 9 days, aimed at improving the microbiological outcome. Histological examinations of the resected infected bone revealed the presence of osteomyelitis in 23 (92%) patients. The healthy margin sample, surgically assessed as non-infected, was confirmed negative in 80% of cases. At a follow-up of 18 ± 7 months, we achieved complete healing in twenty patients (80%), with an average healing time of 70 ± 41 days. No recurrence of osteomyelitis was observed. Conclusions: The data from this study demonstrate that the combination of targeted antibiotic therapy and conservative surgical treatment is effective in resolving osteomyelitis without recurrence with a very long follow-up. Histological analyses allowed us to confirm the actual presence of osteomyelitis and demonstrate that clinical differentiation during surgery is effective in identifying a healthy margin.

Many patients with community-acquired diabetic foot infections (DFI) receive systemic (empirical) antibiotic treatments before surgical interventions, often by the general practitioner. Sometimes, hospital clinicians prescribe them before surgery to reduce the infection inoculum and preserve soft tissue for immediate wound closure in case of residual infection after surgery. In contrast, the international guidelines (IWGDF) advocate against presurgical antibiotic use in routine situations without severe progredient soft tissue infections and/or sepsis. We run several retrospective and prospective cohorts of DFI and retrospectively analyze the influence of presurgical antibiotic therapy (as binary (yes/no) or continuous (in days) variables) on failures after a combined surgical and medical treatment. In our large database, the presence, choice, administration routes, or duration of preoperative antibiotic therapy did not improve the postoperative outcomes of operated diabetic foot infections or prevent their failures. In turn, this lack of influence leaves space for enhanced antibiotic stewardship in the management of DFI.

Empirical antibiotic prescription guidelines were developed at the University Medical Center Ho Chi Minh City in 2020, which included recommendations for the use of antibiotics to treat diabetic foot infections (DFIs). This study investigated the treatment outcomes when implementing empirical antibiotic guidelines. This retrospective study included 120 inpatients with DFIs at the Department of Endocrinology, University Medical Center Ho Chi Minh City. This study had 2 periods (before and after implementation of hospital antibiotic guidelines): Period 1 from July 2019 to June 2020 and Period 2 from July 2021 to June 2022, with 60 random patients in each period. Treatment outcomes were assessed as follows: improvement (defined as the absence of fever and a white blood cell count within the normal range) at 72 hours and 7 days; duration of hospitalization; and clinical status at hospital discharge. After implementing empirical antibiotic guidelines, a greater proportion of improvement in the first 7 days of hospitalization (75.0% vs 56.7%, P = .03), and a shorter median duration of hospitalization (12.5 days vs 15.0 days, P = .02) were observed in patients with DFIs. All the patients showed improvement at the time of hospital discharge. The study findings revealed the encouraging effects of implementing empirical antibiotic prescription guidelines for DFI treatment.

Diabetic foot ulcer (DFU) is a common and complex complication in patients with diabetes mellitus. The study of antibiotic-loaded bone cement for the treatment of infected diabetic foot is limited. We aimed to assess the efficacy of antibiotic-loaded bone cement for the treatment of infected diabetic foot.

The MEDLINE, Embase, BIOSIS, the Cochrane Central Register of Controlled Trials (CENTRAL), and Web of Knowledge databases were systematically searched up to May 2023 with no language restrictions. We assessed eligible studies for the efficacy of antibiotic-loaded bone cement for the treatment of infected diabetic foot. The standard mean differences (SMDs) or the risk ratios (RRs) were calculated for continuous or dichotomous data, respectively. Data were analysed using the Cochrane Collaboration's RevMan 5.0 software.

Nine articles with 565 patients were analysed in our meta-analysis. The wound healing time in ABC group was significantly shorter than that in the control group (SMD = -1.64, 95% CI -2.27 to -1.02 p < 0.00001, I2 = 88%). The ABC group had a significantly decreased number of debridements (SMD = -2.47, 95% CI -4.24 to -0.70, p < 0.00001, I2 = 95%). The pooled data showed no significant difference (RR = 0.41, 95% CI 0.12 to 1.39, p = 0.84, I2 = 0%).

This is the first meta-analysis comparing the efficacy of antibiotic-loaded bone cement for the treatment of infected diabetic foot. Antibiotic-loaded bone cement treatment significantly shortened the wound healing time and reduced the number of debridements without increasing the incidence of complications.

PROSPERO CRD42023406017.