Executive summary: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections

Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.     

A current approach to diabetic foot infections

Foot infections are a common, complex, and serious problem in diabetic patients. Infections usually begin in foo ulcers, which are associated with neuropathy, vasculopathy, and various metabolic disturbances. These infections are potentially limb and sometimes life threatening. Etiologic agents are usually aerobic gram-positive cocci, but chronic or serious infections often contain gram-negative rods and anaerobes. Chronic infections can lead to contiguous bone infection. Diagnosing osteomyelitis may require imaging studies (especially magnetic resonance imaging) and occasionally bone biopsy. In addition to proper cleansing, debridement, and local wound care, diabetic foot infections require carefully selected antibiotic therapy. Serious infections necessitate hospitalization for initial parenteral broad-spectrum antibiotic therapy, but appropriately selected patients with mild infections can be treated as outpatients with oral (or even topical) agents. Initial antibiotic selection is usually empiric; modifications may be needed based on the results of properly obtained cultures and the clinical response. Therapy should be active against staphylococci and streptococci, with broader-spectrum agents indicated if polymicrobial infection is likely. Levels of most antibiotics, except fluoroquinolones, are often subtherapeutic in infected foot tissues. The duration of therapy ranges from a week (for mild soft tissue infections) to over 6 weeks (for osteomyelitis). No single antibiotic agent or combination has proven to be optimal. With appropriate local, surgical, and antimicrobial therapy, most diabetic foot infections can now be successfully treated.     

Expert opinion on the management of infections in the diabetic foot

This update of the International Working Group on the Diabetic Foot incorporates some information from a related review of diabetic foot osteomyelitis (DFO) and a systematic review of the management of infection of the diabetic foot. The pathophysiology of these infections is now well understood, and there is a validated system for classifying the severity of infections based on their clinical findings. Diagnosing osteomyelitis remains difficult, but several recent publications have clarified the role of clinical, laboratory and imaging tests. Magnetic resonance imaging has emerged as the most accurate means of diagnosing bone infection, but bone biopsy for culture and histopathology remains the criterion standard. Determining the organisms responsible for a diabetic foot infection via culture of appropriately collected tissue specimens enables clinicians to make optimal antibiotic choices based on culture and sensitivity results. In addition to culture-directed antibiotic therapy, most infections require some surgical intervention, ranging from minor debridement to major resection, amputation or revascularization. Clinicians must also provide proper wound care to ensure healing of the wound. Various adjunctive therapies may benefit some patients, but the data supporting them are weak. If properly treated, most diabetic foot infections can be cured. Providers practising in developing countries, and their patients, face especially challenging situations.     

Outcomes of subatmospheric pressure dressing therapy on wounds of the diabetic foot

The purpose of this retrospective study was to evaluate outcomes of people with large diabetic foot wounds treated with subatmospheric pressure dressing therapy immediately following surgical wound debridement. Data were abstracted from the medical records of 31 consecutive patients with diabetes, 77.4% male (n = 24), aged 56.1 +/- 11.7 years, presenting for care at two large multidisciplinary wound care centers. All patients received surgical debridement for indolent diabetic foot wounds and were subsequently started on a regimen of subatmospheric pressure dressing therapy delivered using a vacuum-assisted closure device for a mean of 4.7 +/- 4.2 weeks (mode = 2 weeks) using a protocol that called for cessation of therapy when the wound bed approached 100% coverage with granulation tissue with no exposed tendon, joint capsule, or bone. Outcomes evaluated included time to complete wound closure, proportion of patients achieving wound healing at the level of initial debridement, and complications associated with use of the device. The mean duration of wounds before therapy was 25.4 +/- 23.8 weeks. In patients treated with subatmospheric pressure dressing therapy, 90.3% (n = 28) of wounds healed at the level of debridement without the need for further bony resection in a mean 8.1 +/- 5.5 weeks. The remaining 9.7% (n = 3) went on to higher level amputation (below knee amputation = 3.2%, [n = 1] and transmetatarsal amputation = 6.5% [n = 2]). Complications included periwound maceration (19.4% [n = 6]), periwound cellulitis (3.2% [n = 1]), and deep space infection (3.2% [n = 1]). The authors concluded that appropriate use of subatmospheric pressure dressing therapy to achieve a rapid granular bed in diabetic foot wounds may have promise in treatment of this population at high risk for amputation and that a large, randomized trial is now indicated.     

Principles and practice of antibiotic therapy of diabetic foot infections

Foot infections are a common and serious problem in diabetic patients. They usually occur as a consequence of a skin ulceration, which initially is colonized with normal flora, and later infected with pathogens. Infection is defined clinically by evidence of inflammation, and appropriate cultures can determine the microbial etiology. Aerobic gram-positive cocci are the most important pathogens; in chronic, complex or previously treated wounds, gram-negative bacilli and anaerobes may join in a polymicrobial infection. In all diabetic foot infections a primary consideration is whether or not surgical intervention is required, e.g. for undrained pus, wound debridement or revascularization. Antibiotic regimens are usually selected empirically initially, then modified if needed based on results of culture and sensitivity tests and the patient's clinical response. Initial therapy, especially in serious infections, may need to be broad-spectrum, but definitive therapy can often be more targeted. Severe infections usually require intravenous therapy initially, but milder cases can be treated with oral agents. Treatment duration ranges from 1-2 weeks (for mild soft tissue infection) to more than 6 weeks (for osteomyelitis). The choice of a specific agent should be based on the usual microbiology of these infections, data from published clinical trials, the severity of the patient's infection, and the culture results. Extension of infection into underlying bone can be difficult to diagnose and may require imaging tests, e.g. magnetic resonance scans. Cure of osteomyelitis usually requires resection of infected bone, but can be accomplished with prolonged antibiotic therapy. Various non-antimicrobial adjunct therapies may sometimes be helpful. Published in 2000 by John Wiley & Sons, Ltd.     

Diagnosing diabetic foot osteomyelitis

Bone involvement during an infection of the diabetic foot represents a serious complication associated with a high risk of amputation, prolonged antibiotic treatment and hospitalization. Diabetic foot osteomyelitis (DFOs) require a multidisciplinary approach given the usual complexity of these situations. DFO should be suspected in most cases especially in the most severe forms of soft tissue diabetic foot infections (DFIs) where the prevalence of bone infection may be up to 60%. Suspicion is based on clinical signs in particular a positive probe‐to‐bone (PTB) test, elevated inflammatory biomarkers especially erythrocyte sedimentation rate and abnormal imaging assessment using plain X‐ray as a first‐line choice. The combination of PTB test with plain X‐ray has proven effective in the diagnosis of DFO. The confirmation (definite) diagnosis of DFO is based on the results of a bone sample examination obtained by either surgical or percutaneous biopsy. Sophisticated imaging examinations such as Magnetic Resonance Imaging (MRI) and nuclear imaging techniques are useful where doubt persists after first‐line imaging assessment. These techniques may also help localize the bone infection site and increase the diagnostic performance of percutaneous bone biopsy. The quality of the microbiological documentation of DFO is likely to improve the adequacy of the antimicrobial therapy especially when medical (ie, no surgical resection of the infected bone tissues) is considered. The use of new (molecular) techniques for the identification of the bone pathogens have not yet proven superiority on classic cultural techniques for the management of such patients.     

Initial antibiotic therapy for postoperative moderate or severe diabetic foot infections: Broad versus narrow spectrum,empirical versus targeted

Aim

To retrospectively evaluate clinical and microbiological outcomes after combined surgical and medical therapy for diabetic foot infections (DFIs), stratifying between the empirical versus the targeted nature, and between an empirical broad versus a narrow-spectrum, antibiotic therapy.

Methods

We retrospectively assessed the rate of ultimate therapeutic failures for each of three types of initial postoperative antibiotic therapy: adequate empirical therapy; culture-guided therapy; and empirical inadequate therapy with a switch to targeted treatment based on available microbiological results.

Results

We included data from 332 patients who underwent 716 DFI episodes of surgical debridement, including partial amputations. Clinical failure occurred in 40 of 194 (20.6%) episodes where adequate empirical therapy was given, in 77 of 291 (26.5%) episodes using culture-guided (and correct) therapy from the start, and in 73 of 231 (31.6%) episodes with switching from empirical inadequate therapy to culture-targeted therapy. Equally, a broad-spectrum antibiotic choice could not alter this failure risk. Group comparisons, Kaplan–Meier curves and Cox regression analyses failed to show either statistical superiority or inferiority of any of the initial antibiotic strategies.

Conclusions

In this study, the microbiological adequacy of the initial antibiotic regimen after (surgical) debridement for DFI did not alter therapeutic outcomes. We recommend that clinicians follow the stewardship approach of avoiding antibiotic de-escalation and start with a narrow-spectrum regimen based on the local epidemiology.     

Local care and medical treatment for ischemic diabetic ulcers

Optimal medical treatment of ischemic diabetic ulcers is multifactorial. Infection is very common and it is necessary to distinguish between limb or life threatening infections and non-limb-threatening infections. The major pathogen associated with non-limb-threatening infection is staphylococcus aureus; oral antibiotics such as amoxicillin/clavulanate or clindamycin can be used. For severe infection, empiric antibiotic therapy is broader-spectrum covering staphylococci, streptococci, gram-negative bacilli and enterococci; intravenous administration is the rule. Duration of antibiotic therapy depends on severity and depth of infection, and on requirement of surgical debridment. Granulocyte colony-stimulating factor is a growth factor stimulating proliferation and function of neutrophils. As an adjunctive therapy for limb-threatening infections, it is associated with a lower rate of amputation. Increasing arterial perfusion if the patient is unsuitable for reconstructive surgery or angioplasty is desirable. Iloprost is an analogue of epoprostenol with effects on platelet aggregability and vasodilatation. It improves ulcer healing, decreases pain, slightly diminishes the rate of amputation. Systemic hyperbaric oxygen therapy can perhaps improve clinical outcome but additional research is needed to define the specific indications and benefits of this treatment modality. Local care is not rationalized and depends on local habits. Debridment is required. Non necrotic wounds can be covered by modern dressing (hydrophilic dressing, alginates, hydrocolloid). Necrotic wounds are dryed until surgical revascularization, or excised if they are limited and superficial. Pinch grafts are very useful for arterial ulcers. The place of topical growth factor like PDGF (platelet derived growth factor) and of living skin equivalents (dermagraft, apligraf) is not defined in ischaemic diabetic ulcers. Treatment of edema is necessary, because it retards or complicates healing. Inelastic bandages can be useful with good tolerance if ischemia is not critical. Pneumatic foot compression is under evaluation. Electric stimulation could be an adjuncting treatment, but with a problem of compliance. Reducing plantar pressure is always necessary.     

Diagnosis and Management of Candida and Other Fungal Infections of the Head and Neck

Fungi are common inhabitants of the oral and nasal mucosa, and therefore the differentiation between colonization and pathogenicity in the setting of upper respiratory tract infection symptoms can be difficult. Fungal head and neck infections occur in both immunocompetent and immunocompromised persons, and patients with neutropenia, diabetes mellitus, corticosteroid use, and HIV infection are particularly susceptible to serious and potentially life-threatening infections. Invasive fungal head and neck infections generally require extensive surgical debridement and prolonged systemic antifungal therapy, and frequently carry a poor prognosis when the underlying immunosuppression cannot be corrected. In contrast, noninvasive fungal head and neck infections often respond to short courses of systemic or topical antifungal therapy, or require limited surgical debridement alone.     

Bacteriological study of diabetic foot infections

AIMS: The polymicrobial nature of diabetic foot infection has been well documented in the literature. Patients with diabetic foot infection not exposed to antibiotics are not well studied before. The relative frequency of bacterial isolates cultured from community-acquired foot infections that are not exposed to antimicrobial agents for 30 days is studied. In addition, the bacterial comparative in vitro susceptibility to the commonly used antibacterial agents is assessed. METHODS: This is a prospective study in which the infected wounds of 86 consecutive diabetic patients seen in the diabetic foot clinic in Adan Teaching Hospital were cultured when visiting the clinic. The patients did not receive antimicrobial therapy 30 days prior to taking the cultures. The specimen was cultured using aerobic and anaerobic microbiological techniques. Isolates were tested for susceptibility to commonly used antimicrobial therapy. RESULT: Staphylococcus aureus was the most common isolate, being recovered from 38.4% of cases. Other organisms were Pseudomonas aeruginosa (17.5%) and Proteus mirabilis (18%), anaerobic gram-negative organisms (10.5%), mainly Bacteroides fragilis. Imipenem, meropenem, and cefepime were the most effective agents against gram-negative organisms. Vancomycin was the most effective against gram-positive organisms. CONCLUSION: S. aureus and P. aeruginosa were the most common causes of diabetic foot infections. Anaerobic organisms are still a common cause for infection, although the prevalence is less. These wounds may require use of combined antimicrobial therapy for initial management.     

Osteomyelitis

Bone and joint infections are painful for patients and frustrating for both them and their doctors. The high success rates of antimicrobial therapy in most infectious diseases have not yet been achieved in bone and joint infections owing to the physiological and anatomical characteristics of bone. The key to successful management is early diagnosis, including bone sampling for microbiological and pathological examination to allow targeted and long-lasting antimicrobial therapy. The various types of osteomyelitis require differing medical and surgical therapeutic strategies. These types include, in order of decreasing frequency: osteomyelitis secondary to a contiguous focus of infection (after trauma, surgery, or insertion of a joint prosthesis); that secondary to vascular insufficiency (in diabetic foot infections); or that of haematogenous origin. Chronic osteomyelitis is associated with avascular necrosis of bone and formation of sequestrum (dead bone), and surgical debridement is necessary for cure in addition to antibiotic therapy. By contrast, acute osteomyelitis can respond to antibiotics alone. Generally, a multidisciplinary approach is required for success, involving expertise in orthopaedic surgery, infectious diseases, and plastic surgery, as well as vascular surgery, particularly for complex cases with soft-tissue loss.     

Advances in the treatment of diabetic foot infections

Lower extremity infections are frequent causes of substantial morbidity and mortality in the diabetic population, and these infections consume a large portion of resources expended on diabetic complications. Gram-positive cocci, particularly Staphylococcus aureus, are the most important pathogens in diabetic foot infections. These organisms are predominant both in mild infections (which are often monomicrobial), as well as in more severe and chronic infected wounds that more often have a polymicrobial cause. Appropriate clinical assessment and culturing of infections are critical in establishing the presence and severity of infection, in detecting osteomyelitis, and in directing the optimal treatment approach. Following necessary debridement and other surgical interventions (e.g., bone resection, revascularization), appropriate antibiotic therapy is a cornerstone of managing the infected lower extremity. Peripheral vascular (i.e., arterial) insufficiency and the increasing prevalence of antibiotic resistance are primary barriers to successfully managing these infections. Fortunately, alternative delivery systems (e.g., antibiotic beads, impregnated sponges) and novel antibiotics (e.g., levofloxacin, linezolid) are providing possible solutions to the challenges posed by this physically, emotionally, and financially devastating condition.     

Diabetic Foot Infections: Update on Management

Purpose of Review

Diabetic foot infections (DFIs) are common in patients with diabetes mellitus complicated by foot ulcers and can be classified in different categories based on their severity. In this report, we present the diagnosis and management of DFIs according to their classification.

Recent Findings

While appropriate antibiotic regiments and surgical techniques for the treatment of DFIs are well established, new technologies and techniques for example in medical imaging, wound care modalities, and supplementary therapy approaches show potentially promising results in preventing DFIs.

Summary

As with every complex disease, fine tuning DFI management can be challenging as it requires careful evaluation of different parameters. It demands timely action, close collaboration of different specialties, and patient cooperation.

     

Foot ulceration and infections in elderly diabetics

Foot lesions occur commonly among patients with diabetes, particularly the elderly and those with sensory neuropathy. Because of serious or recurrent infections and impaired healing processes, initially trivial lesions may progress to chronic nonhealing wounds, gangrene, or untreatable infections that can lead to limb amputation. Strategies to prevent amputation depend on understanding the multifactorial nature of diabetic foot disease; providing effective ongoing preventive care, including patient education; and prompt and aggressive treatment of foot lesions when they occur. The approach to treatment of infections depends on many factors, including the severity of the soft tissue infection, whether or not underlying bone or joints are involved, the types of infecting organisms, the patient's social situation, and his other medical problems. Proper diagnostic studies followed by appropriate antimicrobial therapy and local wound care can usually lead to resolution of these potentially serious infections.     

Swab cultures accurately identify bacterial pathogens in diabetic foot wounds not involving bone.

AIMS: Current clinical practice assumes swab cultures from wounds are unreliable. However, this assumption is based upon data culled only from wounds in which osteomyelitis and/or gangrene were present. This study aimed to re-evaluate the accuracy of swab cultures vs. deep tissue cultures in diabetic wounds of varying depth and severity. METHODS: A total of 60 infected diabetic foot wounds were cultured. Two specimens were taken from each wound: superficial swab before debridement and deep tissue specimen towards the end of surgical debridement. RESULTS: In 37 wounds (62%), the micro-organisms isolated from the swab specimen and those isolated from the deep tissue specimen were identical. In another 12 wounds (20%), the swab culture contained all micro-organisms isolated from the deep tissue culture, but also contained additional micro-organisms. Analysis according to the depth of the wound, demonstrated that swabs identified all micro-organisms isolated from the deep tissue specimens in 36/40 wounds (90%) that did not extend to bone as opposed to 13/20 wounds (65%) that extended to bone. CONCLUSIONS: Swab cultures are valuable in identifying pathogens in diabetic foot wounds when bone is not involved. When surgical debridement is contraindicated or delayed, swab cultures can be used to select appropriate antibiotic therapy.     

Vibrio vulnificus infection

We report 3 cases of Vibrio vulnificus infections from Taiwan. Patient 1, who manifested symptoms of primary septicemia, died after 2 days. Patient 2, who had a wound infection and signs and symptoms of sepsis but negative blood cultures, responded to tobramycin and chloramphenicol plus surgical debridement, and recovered after 26 days of hospitalization. Patient 3 had secondary septicemia originating from a wound inflicted by a shrimp. Originally, the patient seemed to respond to ceftazidime and amikacin treatment along with surgical debridement, but subsequently died from adult respiratory distress syndrome (ARDS) induced by several episodes of aspiration which occurred after initial clinical improvements. We conclude that, for patients with severe wounds and evidence of V. vulnificus infection, an appropriate, powerful antibiotic, such as one of the third generation cephalosporins should be used as initial therapy unless the nature of the infection indicates other treatment.     

Infections associated with prosthetic knee and prosthetic hip

Arthroplasty of the knee and hip is a common procedure. There is a risk of infection with primary arthroplasty, with an incidence of 1% to 2%. Significant cost and morbidity are associated with infection of the prosthetic joint. Most infections (60% to 70%) are caused by staphylococci, but approximately 10% are caused by streptococci and/or enterococci, whereas the remainder are caused by gram-negative enteric aerobes or anaerobic flora. Surgical revision is often required for cure because the biofilm that adheres to the infected prosthesis precludes antibiotic therapy from being effective. Biofilm formation occurs consistently as a consequence of host protein deposition on the prostheses, which serve as ligands for bacterial receptors. Once established, biofilm infections require removal of the prosthesis in order to effect a cure. Clinical and radiologic features are not specific for the diagnosis. Culture is specific but not sensitive enough to establish a pathogen in all cases. Surgical approaches are varied and range from debridement with retention of the prostheses to amputation of the limb. The most favored approach is the two-stage delayed reimplantation, in which patients receive specific antibiotic therapy for 6 weeks or more. Several additional antibiotics other than vancomycin are available for methicillin-resistant staphylococcal infection, but these are still unproven in the treatment of osteomyelitis or prosthetic joint infection.     

Offloading difficult wounds and conditions in diabetic patient

Wounds in the diabetic population represent a significant medical and economic burden. Early recognition and prompt management can facilitate healing of these wounds. The scope of potential interventions includes debridement, infection control, offloading, protective dressings, active dressings (such as growth factors and living skin constructs), revascularization, proper nutrition, and patient education, If foot pressures are to be reduced, healing to progress, and prevention of ulceration to be a realistic goal, offloading is imperative. The following article discusses offloading of difficult wounds and Charcot foot at various stages of treatment. A user-friendly written and pictorial compendium and an algorithm of care are offered, as well as pedorthic management of foot amputations.     

Outpatient management of uncomplicated lower-extremity infections in diabetic patients

Most diabetic foot infections are believed to be caused by both aerobic and anaerobic bacteria and to require hospitalization and parenteral antimicrobial therapy. We prospectively evaluated diabetic patients with non-limb-threatening lower-extremity infections not yet treated with antibiotics. The patients were randomized to outpatient treatment with oral clindamycin hydrochloride or cephalexin for 2 weeks and evaluated every 3 to 7 days. In 56 assessable patients, curettage yielded a mean of 2.1 microorganisms. Aerobic gram-positive cocci were isolated in 50 cases (89%), and were the sole pathogen in 21 (42%) of these. Aerobic gram-negative bacilli and anaerobes were isolated in 20 (36%) and 7 (13%) cases, respectively, and almost always in polymicrobial infections. Fifty-one infections (91%) were eradicated, 42 (75%) after 2 weeks of treatment; only 5 (9%) were initially treatment failures, and 3 (5%) were subsequently cured with further outpatient oral antibiotic treatment. After a mean follow-up of 15 months, no further treatment was required in 43 (84%) of the cured patients. Previously untreated lower-extremity infections in diabetic patients are usually caused by aerobic gram-positive cocci, and generally respond well to outpatient management with oral antibiotic therapy.     

A retrospective, longitudinal study to evaluate healing lower extremity wounds in patients with diabetes mellitus and ischemia using standard protocols of care and platelet-rich plasma gel in a Japanese wound care program

Chronic wounds, especially in patients with diabetes mellitus (DM), are a major health challenge in Japan. The goal of wound care centers (WCCs) in Japan is to facilitate healing and prevent lower extremity amputations (LEAs) using standardized protocols of patient and wound care. The standard treatment algorithm includes a complete patient and wound assessment, history, physical exam, and a variety of diagnostic tests that determine the need for infection control intervention, revascularization, excision and debridement, growth factor/platelet rich plasma (PRP) gel therapy, skin graft/ flap, wound protection, and education. All patient and wound data are entered in a secure central database for all WCCs. To evaluate the outcomes of standard care regimens compared to the use of a topical PRP gel treatment in patients with a variety of complex wounds, a retrospective, longitudinal study was conducted. Wound outcomes from 39 patients with 40 chronic, nonhealing, lower extremity wounds were evaluated between two time periods: between first presentation at the WCC (T1) and after using standard topical treatments (T2) and between T2 and after using the PRP gel treatment (T3). Patient average age was 66.8 years (SD: 10.60) and mean wound duration was 99.7 days before treatment (SD: 107.73); and the majority of patients (85%) had DM. Wounds were classified as ischemic diabetic (n = 24), diabetic (n = 10), ischemic (n = 5), and pressure ulcer (n = 1). DFUs were Wagner III (77%) and lV (23%). Of those, 60% were in patients with arteriosclerotic obliterans (ASO). Infection (abscess, cellulitis, osteomyelitis, and/or gangrene) was present in all wounds and treated using debridement, antibiotic therapy, and surgery as deemed appropriate. During the first treatment period (T1 to T2) of 75.3 days, which included revascularization and/or debridement along with standard of care, none of the wounds healed and the average wound area, depth, and volume increased. Following topical PRP gel treatment, 83% of wounds healed within 145.2 days (T2 to T3) (P = 0.00002). Only one patient required an LEA. The results of this study suggest that good healing outcomes and a low amputation rate can be obtained with a protocol of supportive care (including revascularization procedures) and the PRP gel treatment. Prospective controlled studies comparing the use of this PRP gel to other advanced treatments are warranted.