A Comprehensive Review of the Pathogenesis, Diagnosis, and Management of Diabetic Foot Infections.

GENERAL PURPOSE: To review an approach to diabetic foot infections (DFIs), including acute osteomyelitis, while also discussing current practices and the challenges in diagnosis and management. TARGET AUDIENCE: This continuing education activity is intended for physicians, physician assistants, nurse practitioners, and nurses with an interest in skin and wound care. LEARNING OBJECTIVES/OUTCOMES: After participating in this educational activity, the participant will1. Identify the risk factors for developing DFIs.2. Outline diagnostic techniques for assessing DFIs.3. Select the assessment techniques that support a diagnosis of osteomyelitis.4. Choose the appropriate pharmacologic and nonpharmacologic treatment options for patients who have DFIs. ABSTRACT: Diabetic foot ulcers result from a combination of peripheral neuropathy, vascular compromise, and repetitive trauma. Approximately 50% of individuals with diabetic foot ulcers will develop a diabetic foot infection (DFI), and 20% of individuals with a DFI will develop osteomyelitis. Herein, the authors review an approach to DFIs including acute osteomyelitis and discuss current practices and challenges in diagnosis and management.The diagnosis of a skin and soft tissue DFI is based on clinical criteria. A bone biopsy is considered the criterion standard for diagnosis of osteomyelitis; however, biopsy is not always feasible or available. Consequently, diagnosis can be made using a combination of clinical, biochemical, and radiographic findings. X-ray is the recommended imaging modality for initial evaluation; however, because of its lower relative sensitivity, advanced imaging may be used when clinical suspicion remains after negative initial testing.The microbiology of skin and soft tissue DFIs and osteomyelitis is similar. Staphylococcus aureus and other Gram-positive cocci are the most common pathogens identified. Deep cultures are preferred in both DFI and osteomyelitis to identify the etiologic pathogens implicated for targeted antimicrobial therapy. Management also requires a multidisciplinary approach. Surgical debridement in those with deep or severe infections is necessary, and surgical resection of infected bone is curative in cases of osteomyelitis. Finally, appropriate wound care is critical, and management of predisposing factors, such as peripheral neuropathy, peripheral arterial disease, tinea, and edema, aids in recovery and prevention.

Retrospective study of the efficacy of vascularized tissue transfer for treating antibiotic-resistant bacteria-infected wound: Comparison with clean and antibiotic-sensitive bacteria-infected wound.

ABSTRACT: If wounds are infected with bacteria resistant to an empirical antibiotic regimen, effective wound treatment will be delayed. This can delay wound healing and lengthen hospital stays, increasing the costs to patients. Long-term antibiotic use can also result in minor and major complications, such as diarrhea, antibiotic resistance, or life-threatening leukopenia. Multidrug-resistant (MDR) bacteria make wound treatment even more difficult. Traditionally, surgeons thought that adequate infection control should be established before soft tissue coverage. However, wounds infected by MDR do not heal well with this traditional method and there are no optimal treatment guidelines for MDR bacteria-contaminated wounds.We reviewed 203 patients who underwent vascularized flap surgery from 2012 to 2019 to cover wounds. Class IV and I wounds were compared according to the Centers for Disease Control and Prevention classification. Class IV was further classified as antibiotic-resistant (ARB) and antibiotic-sensitive (ASB) bacteria. Wound size, mode, location, pathogens, healing time, and basic demographics were evaluated. Data were compared using Cramer's V and one-way ANOVA or independent t tests.The average healing time was longer in the ARB (19.7 [range 7-44] days) and ASB (17.9 [range 2-36] days) groups than in the Clean group (16.5 [range 7-28] days). Healing time differed in the 3 groups (P = .036). It was longer in the class IV group than in the class I group (P = .01). However, it was not statistically different between the ARB and ASB groups (P = .164).In our study the difference in healing time was small when vascularized tissue transfer was done in ARB-infected wound compared with ASB-infected and clean wound. It is necessary to perform surgery using vascularized tissue for the infected wound of antibiotic-resistant bacteria.

The implementation of an infection control bundle within a Total Care Burns Unit.

AIM: To evaluate the impact of the implementation of a best practice infection prevention and control bundle on healthcare associated burn wound infections in a paediatric burns unit. BACKGROUND: Burn patients are vulnerable to infection. For this patient population, infection is associated with increased morbidity and mortality, thereby representing a significant challenge for burns clinicians who care for them. METHODS: An interrupted time series was used to compare healthcare associated burn wound infections in paediatric burn patients before and after implementation of an infection prevention and control bundle. Prospective surveillance of healthcare associated burn wound infections was conducted from 2012 to 2014. Other potential healthcare associated infection rates were also reviewed over the study period, including urinary tract infections, pneumonia, upper respiratory tract infections and sepsis. An infection prevention and control bundle developed in collaboration between the paediatric burn unit and infection control clinicians was implemented in 2013 in addition to previous standard practice. RESULTS: During the study period a total of 626 patients were admitted to the paediatric burns unit. Healthcare associated burn wound infections reduced from 34 in 2012 to 0 in 2014 following the implementation of the infection prevention and control bundle. Pneumonia and sepsis also reduced to 0 in 2013 and 2014, however one upper respiratory tract infection occurred in 2013 and urinary tract infections persisted in 2013. CONCLUSION: The implementation of an infection prevention and control bundle was effective in reducing healthcare associated burn wound infections, pneumonia and sepsis within our paediatric burns unit. Urinary tract infections remain a challenge for future improvement.

Cathelicidin ΔPb-CATH4 derived from Python bivittatus accelerates the healing of Staphylococcus aureus-infected wounds in mice.

The effects of ΔPb-CATH4, a cathelicidin derived from Python bivittatus, were evaluated against Staphylococcus aureus-infected wounds in mice. These effects were comparable to those of classical antibiotics. ΔPb-CATH4 was resistant to bacterial protease but not to porcine trypsin. A reduction in the level of inflammatory cytokines and an increase in the migration of immune cells was observed in vitro. Thus, ΔPb-CATH4 can promote wound healing by controlling infections including those caused by multidrug-resistant bacteria via its immunomodulatory effects.

What Makes Wounds Chronic.

Chronic wounds present a unique therapeutic challenge to heal. Chronic wounds are colonized with bacteria and the presence of a biofilm that further inhibits the normal wound healing processes, and are locked into a very damaging proinflammatory response. The treatment of chronic wounds requires a coordinated approach, including debridement of devitalized tissue, minimizing bacteria and biofilm, control of inflammation, and the use of specialized dressings to address the specific aspects of the particular nonhealing ulcer.

Biofilm and Chronic Nonhealing Wound Infections.

In this review, the author summarizes the role of biofilm formation in chronic nonhealing wound infections along with characteristics of biofilm formation, diagnosis, detection, and treatment. Because biofilms are still not clearly understood, treatment and diagnosis are currently difficult.

Biologic and Synthetic Cellular and/or Tissue-Based Products and Smart Wound Dressings/Coverings.

Cellular and/or tissue-based products (CTPs) have advanced greatly in the past several decades and improve the ability to heal wounds more efficiently. Products can be characterized as nonviable cells, tissue based, animal; nonviable cells, tissue based, human; viable human cells, cultured in vitro, animal substrate; viable human cells, cultured in vitro, synthetic substrate; viable human cells, noncultured, intact tissue. There are approximately 77 different CTPs at the time of this writing, with many more being investigated. Cellular and/or tissue-based product selection, application, postapplication course, and patient selection depend on patient attributes, CTP specifications, and surgeon preference.

Bacteria and Antibiotics in Wound Healing.

This review of the literature concerning bacteria, antibiotics and tissue repair shows there are extensive data supporting microbial interference with wound healing once bacterial burden exceeds 104 CFU per unit of measure, The mechanism of bacterial interference lies largely in prolonging the inflammatory phase of tissue repair. Reducing the microbial bioburden allows tissue repair to continue. Systemic and topical antimicrobials appear critical to reducing the bioburden and facilitating repair. The current controversy over the use of antimicrobials in patients with chronically infected wounds, in particular, revolves around the definition of infection. The reliance on classic clinical signs of inflammation to support antimicrobial use in these patients is tenuous due to the lack of correlation of these signs with the microbial burden known to impair tissue repair.

Functional ambulatory status as a potential adjunctive decision-making tool following wound, level of ischemia, and severity of foot infection assessment.

The Society for Vascular Surgery Lower Extremity Threatened Limb Classification System has been developed to stratify amputation risk on the basis of extent of the wound, level of ischemia, and severity of foot infection (WIfI). However, there are no currently validated metrics to assess, grade, and consider functional status, especially ambulatory status, as a major consideration during limb salvage efforts. Therefore, we propose an adjunct to the current WIfI system to include the patient's ambulatory functional status after initial assessment of limb threat. We propose a functional ambulatory score divided into grade 0, ambulation outside the home with or without an assistive device; grade 1, ambulation within the home with or without an assistive device; grade 2, minimal ambulation, limbs used for transfers; and grade 3, a person who is bed-bound. Adding ambulatory function as a supplementary assessment tool can guide clinical decision making to achieve optimal future functional ambulatory outcome, a patient-centered goal as critical as limb preservation. This adjunct may aid limb preservation teams in rapid, effective communication and clinical decision making after initial WIfI assessment. It may also improve efforts toward patient-centered care and functional ambulatory outcome as a primary objective. We suggest a score of functional ambulatory status should be included in future trials of patients with chronic limb-threatening ischemia.

MMP-9 responsive dipeptide-tempted natural protein hydrogel-based wound dressings for accelerated healing action of infected diabetic wound.

The infected diabetic wound ulcer is a significant problem for the diabetic patients, which leads to removal of affected foot site due to its delayed/non-healing tissues. The poly-microbial infections and active matrix metalloproteinases (MMP) are the significant influencing factors to delayed healing in diabetic mice. The main purposes of present investigation are to evaluation the targeted inactivation of MMP and avoid polymicrobial infections by using a combined therapeutic effect of metal chelating dipeptide (L-carnosine) and curcumin with the biocompatible silk protein hydrogel (L-car@cur/SF) dressing in the infected diabetic wound ulcer. The in vitro biological assay methods, such as, cell viability, anti-oxidant activity, anti-inflammatory macrophage cells and inhibition collagenase exhibited that the designed hydrogel matrix to be human cell compatible and could be accelerate for significant diabetic healing potential. The activation of cur/SF matrix by the L-carnosine was persuading the inactivation of matrix metalloproteinase-9 (MMP-9) through its potent chelating effects of Zn2+ ions from the MMP-9 active center. The L-car@cur/SF hydrogel was demonstrated for the effective MMP-9 inactivation and bacterial inhibition via in vivo mice wound site, which indorsed the diabetic wound healing efficiency in streptozotocin-tempted diabetic mice.

Assessment of the Efficacy of Tributylammonium Alginate Surface-Modified Polyurethane as an Antibacterial Elastomeric Wound Dressing for both Noninfected and Infected Full-Thickness Wounds.

Risk factors of nonhealing wounds include persistent bacterial infections and rapid onset of dehydration; therefore, wound dressings should be used to accelerate the healing process by helping to disinfect the wound bed and provide moisture. Herein, we introduce a transparent tributylammonium alginate surface-modified cationic polyurethane (CPU) wound dressing, which is appropriate for full-thickness wounds. We studied the physicochemical properties of the dressing using Fourier transform infrared, 1H NMR, and 13C NMR spectroscopies and scanning electron microscopy, energy-dispersive X-ray, and thermomechanical analyses. The surface-modified polyurethane demonstrated improved hydrophilicity and tensile Young's modulus that approximated natural skin, which was in the range of 1.5-3 MPa. Cell viability and in vitro wound closure, assessed by MTS and the scratch assay, confirmed that the dressing was cytocompatible and possessed fibroblast migratory-promoting activity. The surface-modified CPU had up to 100% antibacterial activity against Staphylococcus aureus and Escherichia coli as Gram-positive and Gram-negative bacteria, respectively. In vivo assessments of both noninfected and infected wounds revealed that the surface-modified CPU dressing resulted in a faster healing rate because it reduced the persistent inflammatory phase, enhanced collagen deposition, and improved the formation of mature blood vessels when compared with CPU and commercial Tegaderm wound dressing.

A review of interventions to reduce pain in chronic wounds.

Reduction of chronic wound pain has the potential to improve patients' quality of life, expedite the healing process and, ultimately, relieve pressure on community services. Despite this, education on pain assessment in the management of chronic wounds is lacking. This literature review seeks to provide evidence-based recommendations to reduce chronic wound pain and inform the practice of community nurses. The results of a thematic analysis indicate that a honey dressing or native collagen matrix dressing and conditioning exercises for the lower leg can reduce pain, and nitroglycerin ointment is especially effective. The review also highlights the need for an individualised approach to the assessment and treatment of pain in patients with chronic wounds.

Risk Factors for Hand Wound Infections in People with Diabetes: A Case-control Study.

Hand infection has been associated with increased morbidity in people with diabetes mellitus. PURPOSE: This study was conducted to determine risk factors for hand wound infection in patients with diabetes mellitus. METHODS: A 1:3 matched prospective case-control study was conducted from December 2006 to December 2016. All study patients were consecutively identified through the inpatient records upon admission to the University of the Philippines Manila, Philippine General Hospital (Manila, Philippines), for a hand wound infection necessitating surgical treatment and were followed until hospital discharge, wound healing, or death. Adults (≥18 years old) with diabetes mellitus for at least 6 months and with (study group) or without (control group) a hand wound infection were eligible to participate. Persons with a history of amputation or who were in a chronic debilitated state were excluded. Infection was defined as the presence of inflammation and purulent discharge. Eligible control patients were consecutively recruited from the outpatient clinics and were matched to the study patients by age (± 5 years) and gender. Demographic (eg, age, gender, education, occupation, tobacco use) and clinical data (body mass index [BMI], duration of diabetes, HbA1c levels, wound location and duration, delay in treatment, neuropathy, surgical procedures, length of hospital stay, and presence of arteriovenous [AV] fistula) were collected from patient records and entered into Excel spreadsheets for analysis. Regression analysis was performed and reported as odds ratio (OR) with 95% confidence intervals (CI). Level of significance was set P <.05. RESULTS: Participants included 30 study and 90 control patients. No significant differences between study and control patients were noted in terms of BMI, duration of diabetes, presence of peripheral neuropathy, occupation, or education. Significantly more study patients had elevated HbA1c (86 vs. 30; P = .0001), used tobacco (17 vs. 8; P = .0001), and had an AV fistula (3 vs. 0; P = .015). After multivariate analysis, HbA1c ≥48 mmoL/moL (OR = 18.8; 95% CI: 2.3-153.8; P = .006) and tobacco use (OR = 10.7; 95% CI: 3.5-32.7; P = .0001) were identified as independent risk factors for hand/upper extremity infection. CONCLUSION: Patients with diabetes who smoked or exhibited elevated HbA1c levels were at higher risk of having a hand infection. Further research and efforts to help people with diabetes stop smoking and maintain good glycemic control may help decrease the burden of hand infection.

25-Hydroxyvitamin D Deficiency: Impacting Deep-Wound Infection and Poor Healing Outcomes in Patients With Diabetes.

BACKGROUND: The Kingdom of Bahrain has a high incidence of diabetes and associated foot complications. Simultaneously, low 25-hydroxyvitamin D (25[OH]D) levels are common in this population and may be associated with the traditional clothing used in desert climates. METHODS: This investigation compared 25(OH)D levels and glycemic control with quantifiable wound healing parameters in a prospective, analytic, nonexperimental, cross-sectional pilot study. Consecutive consenting adult patients (N = 80) who presented to the regional wound care unit in January 2016 with either an existing or new wound were included. Collected data included three-dimensional wound photography, NERDS and STONEES criteria, and an X-ray with a positive probe-to-bone test. Blood values for 25(OH)D and hemoglobin A1c (HbA1c) were collected simultaneously. RESULTS: Diabetes mellitus (types 1 and 2) was present in 90% of the sample patients. No patient had sufficient 25(OH)D levels; 15% had insufficient levels (30-50 ng/mL), and deficiency (levels <#20 ng/mL) was found in 85% of the sample. Males were slightly less affected by 25(OH)D deficiency compared with females (82.4% vs 91.3%). Poor glycemic control (HbA1c levels >#6.8%) was found in 69.4% (n = 50) of the persons with diabetes included in the sample. Those with both diabetes mellitus and a 25(OH)D deficiency (76.3%; n = 61) were more likely to demonstrate healing difficulty (40.9%; n = 25) or present with a stalled or deteriorating wound (44.2%, n = 27). A 3° F or higher periwound surface temperature elevation over a mirror image site was present in 82.5% of all wounds. Exposed bone in the ulcer base was found in 50% of the cases. For persons with diabetes, general linear modeling statistical analysis (adjusted R value = 47.9%) linked poor wound healing with three studied variables: 25(OH)D deficiency, poor glycemic control, and an exposed bone in the wound bed. CONCLUSIONS: Vitamin D may be an overlooked factor in the pathophysiology of diabetic foot ulcer development and subsequent delay in wound healing outcomes. The authors recommend adding 25(OH)D deficiency to the list of multifactorial aggravating factors providers should consider correcting in this subgroup of patients.

Health-related Quality of Life and Wound Care Practices Among Patients With Chronic Wounds in a Southwestern Nigerian Community

INTRODUCTION: Chronic wounds (CWs) are a common problem around the world. Although known to affect quality of life, patients' perception may vary among cultures. OBJECTIVE: The purpose of this article is to determine the effects of CWs on health-related quality of life (HRQoL) and identify wound care practices among a select population in southwestern Nigeria. MATERIALS AND METHODS: This is a descriptive study of 60 patients with CWs receiving outpatient care. Adult patients > 18 years of age with a wound duration > 3 months were chosen by convenience nonprobability sampling at the point of care. A pretested, semistructured, interviewer-administered questionnaire and a guided interview was provided to each patient to complete; collected data were coded to ensure confidentiality and input into computer software for statistical analysis. RESULTS: The average respondent age was 48.3 years (range, 18-80 years). Male to female ratio was 1:1.2, with 71.7% married, 96.7% of the Yoruba ethnic group, and 40% traders by occupation. The average wound duration was 23.2 months (range, 3-240 months). Trauma was the most common etiology of CWs followed by infection. There was no relationship between wound duration and patients' gender. Most patients accessed care from more than 1 source simultaneously. The presence of CWs adversely affected the quality of life (R = -.288; P = .025). Many patients had varying degrees of abnormality in their mental health. CONCLUSIONS: Chronic wounds are associated with poorer HRQoL, and simultaneous reception of wound care from multiple sources was common. These findings also suggest a need to pay increased attention to psychological aspects of patients with CWs.

Combat-Related Extremity Wounds: Injury Factors Predicting Early Onset Infections.

We examined risk factors for combat-related extremity wound infections (CEWI) among U.S. military patients injured in Iraq and Afghanistan (2009-2012). Patients with ≥1 combat-related, open extremity wound admitted to a participating U.S. hospital (≤7 days postinjury) were retrospectively assessed. The population was classified based upon most severe injury (amputation, open fracture without amputation, or open soft-tissue injury defined as non-fracture/non-amputation wounds). Among 1271 eligible patients, 395 (31%) patients had ≥1 amputation, 457 (36%) had open fractures, and 419 (33%) had open soft-tissue wounds as their most severe injury, respectively. Among patients with traumatic amputations, 100 (47%) developed a CEWI compared to 66 (14%) and 12 (3%) patients with open fractures and open soft-tissue wounds, respectively. In a Cox proportional hazard analysis restricted to CEWIs ≤30 days postinjury among the traumatic amputation and open fracture groups, sustaining an amputation (hazard ratio: 1.79; 95% confidence interval: 1.25-2.56), blood transfusion ≤24 hours postinjury, improvised explosive device blast, first documented shock index ≥0.80, and >4 injury sites were independently associated with CEWI risk. The presence of a non-extremity infection at least 4 days prior to a CEWI diagnosis was associated with lower CEWI risk, suggesting impact of recent exposure to directed antimicrobial therapy. Further assessment of early clinical management will help to elucidate risk factor contribution. The wound classification system provides a comprehensive approach in assessment of injury and clinical factors for the risk and outcomes of an extremity wound infection.

Evaluation of early wound leakage as a risk factor for prosthetic joint infection.

BACKGROUND AND PURPOSE: Prosthetic joint infection (PJI) is a serious complication resulting from total knee arthroplasty (TKA) or total hip arthroplasty (THA). In this study, patients with a PJI are compared with patients with an uncomplicated postoperative course to identify relevant risk factors for PJI. METHODS: A matched case-control study was performed with patients undergoing fast-track, elective unilateral TKA or THA. The following data were collected: demographics, surgery-related characteristics (perioperative blood loss, use of cement, body temperature), and postoperative characteristics (hematoma formation, wound leakage, blood transfusion, length of stay [LOS]). CONCLUSIONS: When the PJI group was compared with the control group, there was significantly more wound leakage during hospital stay (88% vs. 36%, p = .001) and early wound dressing changes in the first 3 days after surgery (88% vs. 40%, p = .002). Hematoma formation was observed more in the PJI patients group (44% vs. 10%, p = .005). A trend test revealed a significant association between the total number of wound dressing changes and development of PJI (p < .001); 72% of PJI patients had a length of stay of ≥4 days compared with 34% of controls (odds ratio 10.5; 95% CI [2.1-52.3]; p = .004). IMPLICATIONS FOR PRACTICE: Early postoperative wound drainage and hematoma formation directly correlate with PJI. This resulted in a significantly higher number of dressing changes and longer LOS. The nurse practitioner has a central role in postoperative care and is the first to recognize signs of an adverse postoperative clinical course.

Targeting miR-223 in neutrophils enhances the clearance of Staphylococcus aureus in infected wounds.

Argonaute 2 bound mature microRNA (Ago2-miRNA) complexes are key regulators of the wound inflammatory response and function in the translational processing of target mRNAs. In this study, we identified four wound inflammation-related Ago2-miRNAs (miR-139-5p, miR-142-3p, miR-142-5p, and miR-223) and show that miR-223 is critical for infection control. miR-223Y/- mice exhibited delayed sterile healing with prolonged neutrophil activation and interleukin-6 expression, and markedly improved repair of Staphylococcus aureus-infected wounds. We also showed that the expression of miR-223 was regulated by CCAAT/enhancer binding protein alpha in human neutrophils after exposure to S. aureus peptides. Treatment with miR-223Y/--derived neutrophils, or miR-223 antisense oligodeoxynucleotides in S. aureus-infected wild-type wounds markedly improved the healing of these otherwise chronic, slow healing wounds. This study reveals how miR-223 regulates the bactericidal capacity of neutrophils at wound sites and indicates that targeting miR-223 might be of therapeutic benefit for infected wounds in the clinic.

The impact of foot infection on infrainguinal bypass outcomes in patients with chronic limb-threatening ischemia.

BACKGROUND: Despite advances in endovascular therapy, infrainguinal bypass continues to play a major role in achieving limb salvage. In this study, we sought to compare outcomes of infrainguinal bypass in patients with limb-threatening ischemia who presented with or without foot infection. METHODS: We conducted a retrospective cohort study of patients who underwent infrainguinal bypass for chronic limb-threatening ischemia at a single institution. End points of interest included long-term mortality, 45-day readmission, postoperative length of stay (LOS), major amputation, and time to wound healing. Multivariable Cox, logistic, and robust regressions were used to model time to event outcomes, readmission rates, and LOS. RESULTS: There were 454 infrainguinal bypass procedures analyzed. Demographics and baseline characteristics were similar, except congestive heart failure and diabetes were more common in the infection group. Presence of foot infection had no impact on mortality (hazard ratio [HR], 0.78; P = .243). Significant predictors of long-term mortality included increasing age, hypoalbuminemia, and congestive heart failure; preoperative use of clopidogrel was protective. Presence of foot infection was an independent predictor of major amputation. In the multiple regression model, the presence of foot infection was independently associated with amputation rate (HR, 2.14; 95% confidence interval, 1.42-3.22; P < .001); use of venous conduit and increasing age and body mass index were protective. Foot infection was an independent predictor of prolonged LOS (mean LOS was 1.54 days longer in patients with vs those without infection; P = .001). Other independent predictors of prolonged LOS included intraoperative blood loss and reoperation; history of continuous preoperative aspirin use and normal baseline renal function and albumin levels were associated with decreased LOS. Readmission was influenced by reoperation (odds ratio [OR], 2.51; P < .001) but not by presence of foot infection (OR, 1.21; P = .349). There was a strong trend for prolonged wound healing time in patients with diabetes (HR, 1.58; P = .05) but not in those with foot infection (OR, 0.74; P = .36). CONCLUSIONS: Among patients requiring infrainguinal bypass for limb-threatening ischemia, infection was more common in patients with diabetes and was a significant predictor of major amputation and prolonged LOS. Infection was not predictive of mortality, wound healing time, or readmission. These findings lend support to the inclusion of infection in risk stratification schemes for patients with chronic limb-threatening ischemia, as recommended in the Society for Vascular Surgery Wound, Ischemia, and foot Infection (WIfI) classification system, because of its adverse impacts on limb salvage.