What Are the Risk Factors for the Development of Diabetic Foot Ulcer?
Answer: The American Diabetic Association has identified the following as general risk factors: 1) diabetes for ≥10 years; 2) male sex; 3) poor glucose control; and 4) presence of cardiovascular, retinal, or renal complications. The following foot-related conditions are associated with increased risk for ulcers and amputation: 1) peripheral sensory neuropathy resulting in the loss of protective sensation; 2) peripheral motor neuropathy resulting in altered biomechanics of the feet as manifested by increased localized pressure on the foot resulting in erythema, and hemorrhage under a callus; 3) peripheral vascular disease manifesting in decreased or absent pulse, or loss of hair and thin, shiny skin; 4) history of foot ulcers or amputation; and 5) severe nail pathology . Lavery et al.  reported that neuropathy, foot deformity, high plantar pressures, and a history of lower extremity amputation are significantly associated with foot ulceration. Vascular and renal diseases are associated with delayed wound healing but are not significantly associated with ulceration per se. Because of the significant role played by neuropathy, it is strongly recommended that the feet of all patients with diabetes should be routinely evaluated for neuropathy. Edelson et al.  found that even in patients hospitalized for acute infected foot, lower extremity examination is not routinely performed. In addition to history, foot wounds should be carefully inspected, pulses palpated, ulcers probed, and neuropathic changes evaluated for sensory and vibratory perception . A monofilament (Semmes–Weinstein 10-g monofilament wire system) is used to test for sensory perception.
How Do the Microorganisms Enter the Foot?
Answer: Bacteria enter the foot most commonly through an open wound such as an ulcer . Less frequently, bacteria enter the foot through the cracks created by tinea pedis (in the webbed space between the toes), paronychia, or direct puncture. Most diabetic foot ulcers are due to a combination of neuropathy (both sensory and motor) and vascular insufficiency. These ulcers are found in areas of the foot where repeated mechanical stress occurs, for example, plantar surface of the metatarsal heads . The area will start out as an area of erythema. A blister and subsequently an ulcer with surrounding callus will develop if irritation continues. Because most of the infections are due to a break in the skin, such as an ulcer or cracks associated with tinea pedis, it is important that measures are taken to prevent these lesions. Prevention of foot irritation can be achieved by advising the patient to use well-fitted shoes.
Is Antibiotic Therapy Indicated for All Patients With Diabetic Foot Ulcer?
Answer: Antibiotic therapy is indicated only in patients whose foot ulcer shows signs of inflammation, has purulent discharge, or has a suspected underlying osteomyelitis . However, when a foot ulcer persists for more than 4 weeks, even in the absence of signs of infection, careful workup should be performed. Therapy of foot ulcer should include antibiotic therapy, off-loading (removal of local irritation either by bed rest or the application of total contact cast), as well as workup for neuropathy and vascular insufficiency. Controlling the infected foot ulcer will improve foot function and quality of life, maintain health status, avoid amputation, and reduce the total cost of care [7–10].
What Are the Common Etiologic Agents Associated With Diabetic Foot Infections?
Answer: When confronted with a patient with suspected infected diabetic foot infection, it is important to determine from the outset the suspected depth of infection to determine the antimicrobial agents for empiric therapy. If possible, cultures should be obtained. In superficial foot infections, gram-positive cocci such as Staphylococcus and Streptococcus are the most common bacteria isolated . In foot infections that involve the deep structures, especially when putrid drainage is present, both aerobic and anaerobic bacteria are commonly isolated . Superficial swab cultures are misleading and should not be performed. After debridement, swab of the tissue may be obtained for culture. Preferably, a culture of tissue aspirate or curettage is submitted for aerobic and anaerobic cultures. Because of the difficulties in growing anaerobes, especially when culture is taken from an open wound, special techniques for transport and culture are needed for better yield. The role of anaerobes in foot infection should not be underestimated. In a study on diabetic foot patients with bacteremia , 5 of 11 bacteremic patients had anaerobes in the blood. Only one of these patients had anaerobes cultured from the infected site. In contrast, all the patients with bacteremia due to aerobic agents had the same organisms grown from the infected foot site.
Which Patients With Diabetic Foot Infections Can Be Treated in the Office?
Answer: Patients with mild superficial infections or non-limb-threatening infections may be treated in the outpatient setting using an oral agent. These patients have a superficial skin infection or ulceration, without purulent discharge, and no cellulitis, osteomyelitis, or systemic toxicity . Patients with manifestations of potentially limb-threatening infections (ulcerations extending to deep tissues, purulent discharge, cellulitis, systemic toxicity, and tissue necrosis with or without osteomyelitis) or life-threatening infections (bacteremia, marked tissue necrosis with or without gangrene, systemic toxicity, and shock) should be hospitalized for more aggressive management of infections as well as glucose control.
Which Antibiotics Are Most Appropriate for the Office Patients With Diabetic Foot Infections?
Answer: Because gram-positive cocci such as Staphylococci and Streptococci are the causative agents in most patients with mild infections, use of oral narrow-spectrum agents has been shown to be effective. Lipsky et al.  compared oral Clindamycin 300 mg every 6 hours with oral Cephalexin 500 mg every 6 hours in the outpatient treatment of these infections and found both drugs when used alone were equally effective. Amoxicillin/clavulanate 500 mg every 8 hours or 875 mg every 12 hours given orally may be effective  (Table 1).
It is important to stress that treatment of the bacterial infections even in mild cases is only part of the overall treatment strategy. Debridement (if needed) should be performed as soon as possible, as should vascular augmentation (if needed), and the events that led to the development should be investigated, for example, repeated stress injury due to an ill-fitting shoe, dermatophyte infection of the foot, and neuropathic foot. The presence of callus is an indication of an ill-fitting shoe or a deformed foot. Pressure relief in the form of shoe modification, orthotics, and occasionally corrective surgery may be necessary.
What Are the Indications for Hospitalization in a Patient With Diabetic Foot Infection?
Answer: All patients with limb- and life-threatening infections as classified by Grayson et al.  should be hospitalized. Patients with ulcers that extend into deep tissues, with surrounding cellulitis, tissue necrosis, osteomyelitis, systemic toxicity, or bacteremia, should be admitted for the initiation of intravenous antimicrobial therapy (with spectrum against aerobes and anaerobes [Table 1]) and surgical intervention. Careful attention should be placed on blood sugar control as well. Delay in intervention is a frequent reason for limb loss.
Which Diagnostic Test Is Most Useful to Detect Osteomyelitis? Which of the Tests for Vascular Disease Should Be Done Routinely on Hospitalized Diabetic Patients With Foot Infection?
Answer: All chronic ulcers should be suspected to have an underlying osteomyelitis and should be probed with a sterile metal probe to determine if the bone can be reached. This simple test was found by Grayson et al.  to have a positive predictive value of 89%. This procedure should be performed only by a practitioner who is familiar with foot anatomy.
Table 2 lists the diagnostic imaging techniques and their sensitivity and specificity. Radiograph of the foot is a cost-effective examination to determine the presence of bone infection . However, because of the poor vascularity in many diabetic patients, radiographic changes of osteomyelitis may not appear even after 2 weeks of infection. Radionuclide scans are more sensitive but have poor specificity. A Technicium bone scan may be positive in the presence of osteomyelitis, fracture, and gout. The test should not be used as a routine screening tool. Leukocyte scans are expensive and may be helpful in differentiating infectious from noninfectious pathology. This test should not be used as a screening tool. Computed tomographic examination and magnetic resonance imaging (MRI) are useful adjunctive measures as well. Because of the presence of inflammation and edema, MRI will show extensive signal abnormalities. MRI should never be used as a substitute for surgery for determining tissue viability or the extent of disease.
Surgical debridement may be used as a diagnostic as well as a therapeutic procedure. Therefore, it is the most expedient and cost-effective method of patient treatment. All ulcers that extend into the deep structures need surgical debridement to determine the depth of the ulcer, the extent of devitalized and infected soft tissue, and the presence of osteomyelitis. Debridement will also reveal the extent of vascularity or lack thereof. If the bone is still viable, bone aspiration or biopsy for histopathology and culture should be performed to confirm the presence of osteomyelitis and to determine the etiologic agent of the infection. Some surgeons prefer to have direct visualization and decide whether to perform local amputation or biopsy.
Noninvasive arterial studies are performed to assess for healing potential of the area supplied by the vessels. Toe pressure waves provide excellent prognostic information . For example, when the toe pressures were greater than 30 mm Hg post–toe amputation, healing is usually successful. In contrast, when the toe pressure was less than 20 mm Hg, only 9% of toe amputation wounds healed. The toe brachial index is a good indicator of flow. A normal toe brachial index is 0.75. An index of less than 0.25 indicates severe occlusive disease. Therefore, toe pressure waves and toe brachial indices should be part of foot evaluation. We do not recommend the use of transcutaneous oxygen to determine vascularity because it is time consuming, it is subject to the experience of technician, and it may miss isolated islands of poor skin vascularity present in many diabetic patients.
When Is Limb Amputation Indicated?
Answer: The ultimate aim in the treatment of an infected diabetic foot is to restore function—specifically ambulation—if possible. Healing will not occur in the presence of devitalized tissues or poor vascularity even with aggressive antimicrobial therapy. Timely surgical consultation and intervention will help restore function early. We have demonstrated that early aggressive surgical debridement and focal toe or transmetatarsal amputation reduced the number of patients requiring above ankle amputation . Function after a ray resection or a transmetatarsal amputation is generally excellent. Ray resection refers to resection of a toe, its proximal metatarsal head, and as much of the diaphysis as necessary to achieve thorough debridement. Patients function well with either a first ray or a fifth ray resection. An isolated midfoot ray resection will also lead to a near normal gait if appropriate orthotic management is instituted. When the disease extends beyond the midfoot, a below-knee amputation should be considered. The prognosis of restoration of ambulation is still good.
What Is the Role of Hyperbaric Oxygen, Growth Factors, and Other Biotech Agents?
Answer: Hyperbaric oxygen may retard progression of a rapidly advancing infection, but it is not a substitute for debridement of all devitalized tissue. The cost-benefit ratio is low, especially when it interferes with surgical debridement. It should be considered as an adjunct treatment to surgical intervention.
The new modalities of treatment should be considered as supplemental therapy to good surgical debridement, appropriate antibiotic therapy, and adequate blood supply. Growth factors will be effective only when the necrotic tissue and debris are removed from the wound, when antibiotic activities are present in the tissues to reduce infection, and when the blood supply is adequate to promote wound healing. Similarly, biografts are used as an adjunctive treatment and will be effective only when the basic wound care has been rendered.
1. American Diabetes Association. Preventive foot care in people with diabetes. Diabetes Care 2001;24:S56–7.
2. Lavery LA, Armstrong DG, Vela SA, et al. Practical criteria for screening patients at high risk for diabetic foot ulceration. Arch Intern Med 1998; 26:157–62.
3. Edelson GW, Armstrong DG, Lavery LA, et al. The acutely infected diabetic foot is not adequately evaluated in an inpatient setting. Arch Intern Med 1996; 156:2373–8.
4. Armstrong DG, Lavery LA, Vela SA, et al. Choosing a practical screening instrument to identify patients at risk for diabetic foot ulceration. Arch Intern Med 1998; 158:289–92.
5. Tan JS, File TMJ. Diagnosis and treatment of diabetic foot infections. Baillieres Best Pract Res Clin Rheumatol 1999; 13:149–61.
6. Sumpio BE. Foot ulcers. N Engl J Med 2000; 343:787–93.
7. American Diabetes Association. Consensus development conference on diabetic foot wound care. Diabetes Care 1999;22:1354–60.
8. Ragnarson-Tenvall G, Apelqvist J. Cost-effective management of diabetic foot ulcers. Pharmacoeconomics 1997; 12:42–53.
9. Ramsey SD, Newton K, Blough D, et al. Incidence, outcomes, and cost of foot ulcers in patients with diabetes. Diabetes Care 1999; 22:382–7.
10. Tan JS, Friedman NM, Hazelton-Miller C, et al. Can aggressive treatment of diabetic foot infections reduce the need for above-ankle amputation? Clin Infect Dis 1996; 23:286–91.
11. Lipsky B, Pecoraro R, Larson S, et al. Outpatient management of uncomplicated lower-extremity infections in diabetic patients. Arch Intern Med 1990; 150:790–7.
12. Sapico FL, Canawati HN, Witte JL, et al. Quantitative aerobic and anaerobic bacteriology of infected diabetic feet. J Clin Microbiol 1980; 12:413–20.
13. Sapico FL, Bessman AN, Canawati HN. Bacteremia in diabetic patients with infected lower extremities. Diabetes Care 1982; 5:101–4.
14. Grayson ML. Diabetic foot infections. Antimicrobial therapy. Infect Dis Clin North Am 1995; 9:143–61.
15. Joseph WS. Treatment of lower extremity infections in diabetics. Drugs 1991; 42:984–96.
16. Grayson ML, Gibbons GW, Balogh K. Probing to bone in infected pedal ulcers: A clinical sign of underlying osteomyelitis in diabetic patients. JAMA 1995; 273:721–3.
17. Eckman M, Greenfield S, Mackey W, et al. Foot infections in diabetic patients. Decision and cost-effectiveness analyses. JAMA 1995; 273:712–20.
18. Seabrook GR, Towne JB. Management of foot lesions in the diabetic patient. In: Rutherford RB, ed. Vascular Surgery. 5th ed. Philadelphia: WB Saunders Co; 2000:1093–1101.
Crerand S, Dolan M, Laing P, et al. Diagnosis of osteomyelitis in neuropathic foot ulcers. J Bone Joint Surg 1996; 78BR:51–55.
Cook TA, Rahim N, Simpson HC, et al. Magnetic resonance imaging in the management of diabetic foot infection. Br J Surg 1996; 83:245–8.
Croll SD, Nicholas GG, Osborne MA, et al. Role of magnetic resonance imaging in the diagnosis of osteomyelitis in diabetic foot infections. J Vasc Surg 1996; 24:266–70.
Keenan AM, Tindel NL, Alavi A. Diagnosis of pedal osteomyelitis in diabetic patients using current scintigraphic techniques. Arch Intern Med 1989; 149:2262–6.
Lipman BT, Collier BD, Carrera GF, et al. Detection of osteomyelitis in the neuropathic foot: nuclear medicine, MRI and conventional radiography. Clin Nucl Med 1998; 23:77–82.
Blume PA, Dey HM, Daley LJ, et al. Diagnosis of pedal osteomyelitis with Tc99m HMPAQ labeled leukocytes. J Foot Ankle Surg 1997; 36:120–6.