Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus (IWGDF 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This is the first guideline on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes published by the IWGDF. We followed the GRADE Methodology to devise clinical questions in the PACO (Population, Assessment, Comparison, Outcome) and PICO (Population, Intervention, Comparison, Outcome) format, conducted a systematic review of the medical literature, and developed recommendations with the rationale. The recommendations are based on the evidence from our systematic review, expert opinion when evidence was not available, and also taking into account weighing of the benefits and harms, patient preferences, feasibility and applicability, and costs related to an intervention. We here present the 2023 Guidelines on the diagnosis and treatment of active Charcot neuro-osteoarthropathy in persons with diabetes mellitus and also suggest key future topics of research.

Diagnosis and treatment of active charcot neuro-osteoarthropathy in persons with diabetes mellitus: A systematic review.

BACKGROUND: There are uncertainties regarding the diagnostic criteria, optimal treatment methods, interventions, monitoring and determination of remission of Charcot neuro-osteoarthropathy (CNO) of the foot and ankle in people with diabetes mellitus (DM). The aims of this systematic review are to investigate the evidence for the diagnosis and subsequent treatment, to clarify the objective methods for determining remission and to evaluate the evidence for the prevention of re-activation in people with CNO, DM and intact skin. METHODS: We performed a systematic review based on clinical questions in the following categories: Diagnosis, Treatment, Identification of Remission and Prevention of Re-Activation in people with CNO, DM and intact skin. Included controlled studies were assessed for methodological quality and key data from all studies were extracted. RESULTS: We identified 37 studies for inclusion in this systematic review. Fourteen retrospective and observational studies relevant to the diagnosis of active CNO with respect to clinical examination, imaging and blood laboratory tests in patients with DM and intact skin were included. We identified 18 studies relevant to the treatment of active CNO. These studies included those focused on offloading (total contact cast, removable/non-removable knee high devices), medical treatment and surgical treatment in the setting of active CNO. Five observational studies were identified regarding the identification of remission in patients who had been treated for active CNO. We did not identify any studies that met our inclusion criteria for the prevention of re-activation in patients with DM and intact skin who had been previously treated for active CNO and were in remission. CONCLUSIONS: There is a paucity of high-quality data on the diagnosis, treatment, and prognosis of active CNO in people with DM and intact skin. Further research is warranted to address the issues surrounding this complex disease.

Biomarkers for Early Detection of Charcot Arthropathy: A Prospective Study on Type 2 Diabetes Patients with Severe Neuropathy.

BACKGROUND: Charcot arthropathy (CA) is a progressive noninfectious inflammatory disease that causes irreversible destruction to pedal architecture in diabetic neuropathy (DN) patients. The debilitating prognosis demands early detection to prevent the development and progression of this disorder. Dysregulated and persistent production of inflammatory cytokines is reported as the key element in initiating osteoclastogenesis in CA. The study analyzed the potential association of markers of inflammation and bone turnover of prediagnostic serum samples on CA. METHODS: Seventy-one type 2 severe DN patients were selected based on inclusion-exclusion criteria. Serum samples of interleukin 6 (IL-6), osteoprotegerin (OPG), bone alkaline phosphatase (BALP), and C-reactive protein (CRP) were analyzed. These patients were followed for the development of symptoms of CA for 12 months. In the year of monitoring, 7 patients developed CA (group 1), whereas the remaining 64 patients did not develop CA (group 2). RESULTS: The rate of development of CA in patients with severe DN was 9.8%. In this group, significantly increased median values of HbA1c (group 2: 8.00 [7.00-9.00], group 1: 10.00 [9.25-11.50], P = .013); IL-6 (group 2: 1.21 [0.72-2.16], group 1: 11.08 [6.65-63.64], P = .008); and CRP (group 2: 1.25 [0.78-3.20], group 1: 3.31 [1.18-41.33], P = .041) were found. The receiver operating characteristic analysis showed that IL-6 was more strongly associated with the onset of CA (IL-6: area under the curve = 0.808; P = .008) than CRP. Cut-off values of ≥6.6 for IL-6 show potential to rule out CA in high-risk patients, with a positive predictive value of 26.1%, a negative predictive value of 97.9%, a sensitivity of 85.7%, and a specificity of 73.4%. CONCLUSION: In our study population, we found that an exacerbated inflammatory state, reflected by IL-6 values, generally occurred in DN patients before the clinical detection of CA. LEVEL OF EVIDENCE: Level II, prospective comparative study.

Novel Topical Esmolol Hydrochloride (Galnobax) for Diabetic Foot Wound: Phase 1/2, Multicenter, Randomized, Double-Blind, Vehicle-Controlled Parallel-Group Study.

We aimed to assess safety and dose-finding efficacy of esmolol hydrochloride (Galnobax) for healing of diabetic foot ulcer (DFU). This is phase 1/2 multicenter, randomized, double-blind vehicle-controlled study. Participants having diabetes and noninfected, full-thickness, neuropathic, grade I or II (Wagner classification) DFU, area 1.5-10 cm2, and unresponsive to standard wound care (at least 4 weeks) were randomized to receive topical Galnobax 14% twice daily (BID), Galnobax 20% BID, Galnobax 20% once daily (OD)+vehicle, or vehicle BID with standard of care. The primary efficacy end point was the reduction in area and volume of target ulcer from baseline to week 12 or wound closure, whichever was earlier. The wound duration was 12.5 weeks (5-49.1 weeks) and wound area 4.10 ± 2.41 cm2 at baseline. The ulcer area reduction was 86.56%, 95.80%, 80.67%, and 82.58% (p = 0.47) in the Galnobax 14%, Galnobax 20%, Galnobax20%+vehicle, and vehicle only groups, respectively. Ulcer volume reduction was 99.40% in the Galnobax14%, 83.36% in Galnobax20%, 55.41% in the Galnobax20%+vehicle, and 84.57% in vehicle group (p = 0.86). The systemic concentration of esmolol was below the quantification limit (10 ng/mL) irrespective of doses of Galnobax (Cmax esmolol acid 340 ng/mL for 14% Galnobax, AUC 2.99 ± 4.31 h*µg/mL after single dose). This is the first clinical study of the short acting beta blocker esmolol hydrochloride used as novel formulation for healing of DFU. We found that esmolol when applied topically over wounds had minimal systemic concentration establishing its safety for wound healing in patients with diabetes. Esmolol hydrochloride is a safe novel treatment for DFU.

Efficacy and Safety of Topical Solution of Diperoxochloric Acid for Neuropathic Diabetic Foot Ulcer: Results from a Phase 3, Multicentre, Randomized, Active-controlled, Parallel-group Study.

Diabetic foot ulcer (DFU), if untreated, accounts for lower-limb amputations affecting patients' quality-of-life. Diperoxochloric acid (DPOCL) is known to heal DFU by its antibacterial and fibroblast stimulating activity. This was a phase 3, multicentre, randomized, double-blind, active-controlled, parallel-group study conducted to evaluate the efficacy and safety of topic solution of DPOCL compared with isotonic sodium chloride solution (ISCL). Adult patients with type 1 or 2 diabetes with random blood glucose levels of <250 mg/dL, with ≤ than three full-thickness foot ulcers were enrolled. Primary efficacy endpoint was complete wound closure and secondary was wound surface area. Adverse events were analyzed as safety endpoint. Of 311 enrolled patients, 289 were randomized 1:1 to DPOCL (139) and ISCL (150) treatment (10-weeks [8-Visits]). Percentage of patients with complete wound closure at visit-8, were significantly higher (P = .0156) in DPOCL arm (76% [105/139]) compared to ISCL (62% [93/150]) arm. At end-of-study, mean wound surface area in DPOCL arm (0.639 cm2) was significantly lower (P = .0209) compared to ISCL (0.818 cm2) arm. One death was reported in control arm which was not considered as treatment-related. No important safety finding were observed. Results indicate that, DPOCL can be considered as effective and safe treatment option for DFU compared to ISCL, although future confirmatory studies are warranted.

Intensive Glycemic Control for Diabetic Foot Ulcer Healing: A Multicentric, Randomized, Parallel Arm, Single-Blind, Controlled Study Protocol (INGLOBE Study).

Hyperglycemia impairs healing of diabetic foot ulcer (DFU). But there is no evidence regarding benefit of intensive glucose control for healing of DFU. We plan to conduct a randomized, parallel arm, controlled study to assess the role of intensive glycemic management in comparison to conventional glucose control for healing of DFU. Participants with neuropathic DFU (infected or uninfected) having hemoglobin A1c (HbA1c) >8% and without evidence of osteomyelitis from 7 tertiary care hospitals will be enrolled. They will undergo a 2-week run-in phase for optimization of comorbidities, ulcer debridement, and counseling regarding self-monitoring of blood glucose (SMBG). Subsequently, they will be randomized to "intensive glycemic control" arm defined by glycemic targets of fasting blood glucose (FBG) <130 mg/dL, postprandial BG <180 mg/dL, and HbA1c <8%, with basal-bolus insulin regimen and frequent titration of insulin to achieve glycemic targets. The "conventional" arm will continue on prior treatment (oral antidiabetic drugs) with no titration unless meeting rescue criteria. Ulcer area will be calculated by automated wound assessment device (WoundlyClinial app) weekly for first 4 weeks, and less frequently until the 24th week. Standard treatment for DFU, off-loading, and counseling for foot care will be provided in both arms. The primary outcome measure will be number of wounds closed at 12th and 24th weeks. A multivariate regression analysis will be performed to identify the predictors of wound healing with baseline HbA1c, diabetes duration, wound size, wound duration, and background therapies as independent variable. This study will provide the much needed guidance to set optimum glucose targets in people with DFU.

Surgical strategies for prevention of amputation of the diabetic foot.

Prevention of amputation has become a key objective of clinicians providing care to patients with high-risk diabetic foot problems. In this regard, the multidisciplinary diabetic foot team (MDFT) has been embraced as the most effective way to manage patients with foot ulcers, infections, and Charcot feet. Importantly, such specialized teams have also integrated various surgical specialties to enable more expedient management of these often complex conditions. Experienced diabetic foot surgeons over the last three or four decades have contributed much to this discipline, whereby foot-sparing reconstructive procedures or minor amputations have become fundamental strategies for limb preservation teams. Central to limb salvage, of course, is the recognition of underlying vascular insufficiency and the importance of prompt (endo)vascular intervention. Restoration of adequate perfusion is essential to allow the podiatric, orthopaedic, or plastic surgeon to perform indicated functional reconstructive or minor amputation procedures. This evidence-based overview discusses the various indications and surgical principles inherent in modern concepts aimed at preventing amputation in the high-risk diabetic foot.

Long term outcomes after incident diabetic foot ulcer: Multicenter large cohort prospective study (EDI-FOCUS investigators) epidemiology of diabetic foot complications study: Epidemiology of diabetic foot complications study.

AIMS: This long-term prospective study evaluated limb amputation and mortality after the first neuropathic diabetic foot ulcer (DFU). METHODS: A total of 2880 patients with neuropathic DFU (DFU group) and a similar number of patients of diabetes without DFU (nDFU) matched for age and diabetes duration were prospectively assessed at five referral-centers over 14 years. Pre-defined outcome was death during follow-up. Various diabetic co-morbidities and amputation were assessed as mortality predictors. RESULTS: Overall, 501 (17.4%) patients in DFU group died compared to 89 (3.1%) (p < 0.01) in nDFU group during a median follow-up of 7(1-14) years. The 5- and 10-year mortality was 22% and 71% in the DFU group with a median survival of 7.72 (7.37-8.08) years compared to 3% (p < 0.01) and 5% (p < 0.01) and survival of 12.6 (10.5-12.7) years (p < 0.001) in nDFU group. 29.3% patients had limb amputations. The mortality risk was independent of glycemic control [OR 1.03 (0.80-1.32; p = 0.83)]. However, diabetes duration > 10 years [OR 1.31(1.02-1.70, p = 0.035)], nephropathy [OR 1.47 (1.04-2.09, p < 0.030)], minor 1.85 (1.40-2.44; p < 0.001) or major amputation 2.96 (2.01-4.34, p < 0.001)] predicted mortality. CONCLUSIONS: Every one-in-three individual with neuropathic DFU has amputation and every sixth individual has an early demise. Prevalent nephropathy and incident amputation following DFU predicts mortality.

Microscopic study of chronic charcot arthropathy foot bones contributes to understanding pathogenesis - A preliminary report.

INTRODUCTION: Charcot arthropathy (CA) is non-infective, chronic destructive condition affecting the pes architecture of long standing diabetic patients with neuropathy. Even though several theories have emerged to disclose its pathogenesis, inflammatory cytokine induced osteoclastogenesis stands as the chief culprit. Studies on micro-architecture of foot bones of acute stage CA patients, describes mainly destructive phase of bone remodelling. Increased osteoclast cell activity is reported in all studies communicated. No study has to the best of our knowledge detailed the microscopic structure of chronic stage CA foot bones. AIM: To study the microscopic structure of foot bones in patients with chronic CA. MATERIALS AND METHODS: Foot bones were collected from the feet of chronic CA patients (six in number) who underwent corrective foot surgery in the Department of Podiatric Surgery of a tertiary care hospital. Control samples were collected from the feet of age matched non-diabetic controls (2 in number). The samples were fixed in formalin, decalcified in 10% nitric acid, processed, sectioned and stained with haematoxylin and eosin. Histopathology and histomorphometry analysis were performed by two different pathologists. RESULTS: Trabeculae of chronic CA foot bones exhibited mainly a lamellar architecture, with reduced number of osteocytes and plenty of empty lacunae. Trabecular connectivity was lost and trabeculae showed considerable thinning. Trabecular osteoids lined by active osteoblast cells was a remarkable observation. Bone area was also considerably reduced in chronic CA foot bones. CONCLUSION: Chronic stage CA foot bones presented features of both healing and fragile bone. The compromised bone quality may be due to thin and fragmented trabecular structure and reduced cellularity.

Emergence of Fluconazole-resistant Candida Infections in Diabetic Foot Ulcers: Implications for Public Health.

BACKGROUND: It is well documented in the literature that fungal infections are common in diabetic foot ulcers (DFUs). This has led to an overuse of antifungal agents, namely fluconazole, with a consequent risk of emergence of resistance to this drug. Previous studies have shown a 3.9% prevalence of fluconazole resistance in DFU, but limited data exist regarding the change in resistance pattern over the last decade. OBJECTIVES: Our aim was to study the prevalence of resistance to fluconazole in patients with DFU and culture-proven fungal infections. MATERIALS AND METHODS: We retrospectively studied 1438 patients with type 2 diabetes and nonhealing foot ulcers who had fungal cultures performed during the course of their treatment. The data were collected for all patients who presented to our foot clinic over a period of 18 months. RESULTS: The prevalence of positive fungal culture was 17.38% (250/1438). 151/200 positive cultures belonged to Candida species. Resistance to fluconazole was observed in 9.3% (17/200). The most common organism with resistance to fluconazole was Candida auris (10/17). CONCLUSIONS: High prevalence of fluconazole resistance is a potential cause of concern, and the rational use of this drug is important in the community. The above results could have an impact on public health, as fluconazole is one of the safest and effective oral antifungal agents available. The spread of resistance could have implications for its use in other situations including systemic fungal infections.

Role of Procalcitonin as a Predictor of Clinical Outcome in Acute Diabetic Foot Infections: A Prospective Study.

BACKGROUND: Prediction of outcome in diabetic foot infection (DFI) remains difficult due to lack of active signs of infection, and apparently normal white blood cell (WBC) count. Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) have been studied previously in this regard and were not useful. Hence, we evaluated procalcitonin (PCT) as a prognostic marker in this study. OBJECTIVES: We aimed to study the role of PCT, CRP, and ESR levels in predicting clinical outcome of acute DFI. MATERIALS AND METHODS: A total of 250 subjects (197 men, 53 women) with acute DFI were enrolled. WBC count, ESR, CRP, and PCT were done for all subjects at admission after obtaining informed consent. Subjects were managed according to hospital protocol and followed up for 1 month. Clinical outcome was assessed based on mobility and morbidity status of the subject. RESULTS: Old age, anemia, hyponatremia, hypoalbuminemia, and elevated serum creatinine were risk factors for poor outcome. Presence of cardiac failure, diabetic retinopathy, peripheral vascular disease, previous amputations, and positive bone culture had negative influence on clinical outcome. Elevated WBC count, ESR, CRP, and serum PCT were significantly associated with bad outcome. Elevated PCT (>2 ng/ml) [odds ratio (OR) (95% confidence interval (CI)), 2.03 (1.13-5.19), P < 0.001], gangrene [OR (95% CI), 2.2 (1.02-4.73), P = 0.04], and sepsis [OR (95% CI), 10.101 (4.34-23.25), P < 0.001] were good predictors of clinical outcome in acute DFI. CONCLUSION: PCT proved to be a reliable marker of acute DFI and good predictor of clinical outcome than existing markers WBC count, ESR, and CRP. Hence it should be useful for clinicians while managing acute DFI.

Epidemiology of diabetic foot infections in a reference tertiary hospital in India

Abstract Introduction The present study attempts to examine the microbial profile and antibiotic susceptibility of diabetic foot infections in the intensive care unit of a tertiary referral centre for diabetic foot. As part of the study, we also attempted to find the prevalence of blaNDM-like gene among carbapenem-resistant gram negative infections. Methodology A prospective study of 261 patients with diabetic foot infections was performed during the period between January 2014 and June 2014. Results A total of 289 isolates were obtained from 178 tissue samples from 261 patients, 156 (59.7%) males and 105 (40.2%) females, with a mean age of 58 years (-15 years), having diabetic foot infection. No growth was seen in thirty eight (17.6%) tissue samples. Out of the total samples, 44.3% were monomicrobial and 55.7% were polymicrobial. Gram negative pathogens were predominant (58.5%). Seven of the total isolates were fungal; 0.7% showed pure fungal growth and 1.7% were mixed, grown along with some bacteria. The most frequently isolated bacteria were Staphylococcus aureus (26.9%), followed by Pseudomonas aeruginosa (20.9%). Of the 58.5% gram negative pathogens, 16.5% were Enterobacteriaceae resistant to carbapenems. Among these isolates, 4 (25%) were positive for blaNDM-like gene. Among the rest, 18.6% were carbapenem-resistant Pseudomonas, among which 4 (36.3%) were blaNDM. Among the Staphylococci, 23.7% were methicillin-resistant Staphylococcus aureus. Conclusions Our results support the recent view that gram negative organisms, depending on the geographical location, may be predominant in DFIs. There is an increase in multidrug-resistant pathogens, especially carbapenem resistance and this is creeping rapidly. We need to be more judicious while using empiric antibiotics.

Epidemiology of diabetic foot infections in a reference tertiary hospital in India.

INTRODUCTION: The present study attempts to examine the microbial profile and antibiotic susceptibility of diabetic foot infections in the intensive care unit of a tertiary referral centre for diabetic foot. As part of the study, we also attempted to find the prevalence of blaNDM-like gene among carbapenem-resistant gram negative infections. METHODOLOGY: A prospective study of 261 patients with diabetic foot infections was performed during the period between January 2014 and June 2014. RESULTS: A total of 289 isolates were obtained from 178 tissue samples from 261 patients, 156 (59.7%) males and 105 (40.2%) females, with a mean age of 58 years (-15 years), having diabetic foot infection. No growth was seen in thirty eight (17.6%) tissue samples. Out of the total samples, 44.3% were monomicrobial and 55.7% were polymicrobial. Gram negative pathogens were predominant (58.5%). Seven of the total isolates were fungal; 0.7% showed pure fungal growth and 1.7% were mixed, grown along with some bacteria. The most frequently isolated bacteria were Staphylococcus aureus (26.9%), followed by Pseudomonas aeruginosa (20.9%). Of the 58.5% gram negative pathogens, 16.5% were Enterobacteriaceae resistant to carbapenems. Among these isolates, 4 (25%) were positive for blaNDM-like gene. Among the rest, 18.6% were carbapenem-resistant Pseudomonas, among which 4 (36.3%) were blaNDM. Among the Staphylococci, 23.7% were methicillin-resistant Staphylococcus aureus. CONCLUSIONS: Our results support the recent view that gram negative organisms, depending on the geographical location, may be predominant in DFIs. There is an increase in multidrug-resistant pathogens, especially carbapenem resistance and this is creeping rapidly. We need to be more judicious while using empiric antibiotics.

A comparative study of zoledronic acid and once weekly Alendronate in the management of acute Charcot arthropathy of foot in patients with diabetes mellitus.

AIM: The aim of this study was to assess and compare the response to two forms of treatment-immobilization with zoledronic acid injection and immobilization with oral weekly Alendronate, in patients with diabetes mellitus and acute Charcot arthropathy (CA) of foot in terms of clinical and radiological parameters. MATERIAL AND METHODS: Patients attending the endocrinology and podiatry clinic with history of diabetes mellitus and Acute CA were taken for study. The patients were randomized into two treatment groups. Group Z-zoledronic acid injection along with total contact cast (TCC). Group A-Tab. Alendronate 70 mg. once a week till the complete clinical resolution of acute CA along with TCC. Forty-five patients were randomized and 40 of them completed the study. The primary end point was complete clinical resolution of acute CA-defined as temperature difference between normal and affected foot <1°F. RESULTS: Among the 40 patients, 30 (75%) had complete clinical resolution. The mean number of days taken for complete clinical resolution since the initiation of treatment (either Zoledronic acid or Alendronate) was approximately 122 days. There was no significant difference in a number of days required for complete clinical resolution, between the two forms of therapy. There was more than 50% reduction in the visual score between the baseline and the final scan. The target to non-target ratio in the skeletal phase also showed an average of 40% reduction from the baseline to the final skeletal scintigraphy. CONCLUSION: Both Intravenous Zoledronic acid and oral alendronate had comparable efficacy with respect to the time taken for attaining complete clinical resolution of acute CA of foot. However, Alendronate therapy was cost effective among the two. (99m)Tc MDP bone scan can be used as an adjuvant to the clinical parameters in assessing the response to therapy.

Foot care practice - the key to prevent diabetic foot ulcers in India.

BACKGROUND: The magnitude of diabetic foot ulcers (DFUs) and the amputation rates due to DFUs remain high even in developing and developed countries. Yet, the influence of knowledge, attitude, and practice (KAP) of diabetic foot care (DFC) on DFU incidence is not studied much. OBJECTIVE: To study causal relationship between knowledge, attitude and practice (KAP) on DFC between diabetic patients with and without DFUs; and the risk factors associated with DFUs. METHODS: A consecutive of 203 diabetic patients (103 with DFU and 100 without DFU) were included in the study. Their demographic details, medical history, and personal habits were recorded. KAP on DFC was assessed using a questionnaire. Responses were recorded, scored, and analyzed. RESULTS: Of the cohort, 67.5% were males, mean age: 59.9 ± 11.4 years. Patients without DFU had good knowledge on DFC compared to those with DFU (86% versus 69.9%) (p<0.001). Incidence of DFU was 9% and 39.8% (p<0.001) among patients who practiced and not practiced DFC respectively. 88% patients with and without DFUs; showed favorable attitude toward adopting DFC. Risk factors - diabetic peripheral neuropathy, peripheral vascular disease, retinopathy, nephropathy, smoking, tobacco chewing and alcohol consumption were significantly (p<0.001) associated with DFUs. CONCLUSIONS: An inverse relationship between DFU and foot care knowledge as well as practice was observed. Apart from tight glycemic control, diabetic patients must be educated and motivated on proper foot care practice and life style modifications for preventing DFUs.

Cost of treating diabetic foot ulcers in five different countries.

Most estimates in the literature for the economic cost of treating a diabetic foot ulcer (DFU) are from industrialized countries. There is also marked heterogeneity between the complexity of cases considered in the different studies. The goal of the present article was to estimate treatment costs and costs to patients in five different countries (Chile, China, India, Tanzania, and the United States) for two hypothetical, but well-defined, DFUs at the extreme ends of the complexity spectrum. A co-author, who is a treating physician in the relevant country, was asked to choose treatment plans that represented the typical application of local resources to the DFU. The outcomes were pre-defined as complete healing in case 1 and trans-tibial amputation in case 2, but the time course of treatment was determined by each investigator in a manner that would be typical for their clinic. The costs, in local currencies, for each course of treatment were estimated with the assistance of local hospital administrators. Typical reimbursement scenarios in each country were used to estimate the cost burden to the patient, which was then expressed as a percentage of the annual per capita purchasing power parity-adjusted gross domestic product. There were marked differences in the treatment plans between countries based on the availability of resources and the realities of local conditions. The costs of treatment for case 1 ranged from Int$102 to Int$3959 in Tanzania and in the United States, respectively. The cost for case 2 ranged from Int$3060 to Int$188,645 in Tanzania and in the United States, respectively. The cost burden to the patient varied from the equivalent of 6 days of average income in the United States for case 1 to 5.7 years of average annual income for case 2 in India. Although these findings do not take cost-effectiveness into account, they highlight the dramatic economic burden of a DFU for patients in some countries.

Spectrum and prevalence of fungi infecting deep tissues of lower-limb wounds in patients with type 2 diabetes.

The prevalence rate and spectrum of fungi infecting deep tissues of diabetic lower-limb wounds (DLWs) have not been previously studied. Five hundred eighteen (382 male and 136 female) consecutive patients with type 2 diabetes hospitalized due to infected lower-limb wounds were enlisted in this study. Deep tissue (approximately 0.5- x 0.5-cm size) taken perioperatively from the wound bed was cultured for fungi. Fungi was found in 27.2% (141/518) of the study population. Candida parapsilosis (25.5%), Candida tropicalis (22.7%), Trichosporon asahii (12.8%), Candida albicans (10.6%), and Aspergillus species (5.0%) were the most predominant fungal isolates. Of the fungal isolates, 17.7% were resistant to itraconazole, 6.9% were resistant to amphotericin B, 6.9% were resistant to voriconazole, 3.9% were resistant to fluconazole, and 1.5% were resistant to flucytosine. Of the population, 79.7% (413/518) had bacterial infection in deep tissue. The predominant isolates were Enterococcus faecalis (14.1%), Staphylococcus aureus (12.2%), and Pseudomonas aeruginosa (10.8%). Mixed fungal and bacterial infections were seen in 21.4% of patients, while 5.8% had only fungal infection and 58.3% had only bacterial infections. Another 14.5% had neither bacteria nor fungi in the deep tissue. Patients with higher glycosylated hemoglobin levels had significantly more fungal infections. Our study reveals that deep-seated fungal infections are high in DLWs. In the context of delayed wound healing and amputation rates due to DLWs, it is important to study the pathogenicity of fungi in deep tissues of DLWs and their possible contribution to delayed wound healing. The role of antifungal agents in wound management needs to be evaluated further.