An evidence-based approach to diabetic foot infections

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Abstract

Foot infections are a major complication of diabetes mellitus and contribute to the development of gangrene and lower extremity amputation. Recent evidence indicates that persons with diabetes are at greater risk for infection because of underlying neuropathy, peripheral vascular disease, and impaired responses to infecting organisms. This article reviews the underlying pathophysiology, causes, microbiology, and current management concepts for this potentially limb-threatening complication. Multidisciplinary management consisting of teams of specialists with a focus on limb preservation can make significant improvements in outcomes, including a reduction in rates of lower extremity amputation.

Section snippets

Pathophysiology

Although not all foot infections are the result of bacterial invasion of ulcerations, this sequence of events is a common pathway leading to serious diabetic lower extremity sepsis. Predisposing factors for limb-threatening lower extremity infection are similar to those for ulceration and include neuropathy, macrovascular and microvascular impairments, as well as decreased resistance to infection, which is often referred to as immunopathy [19], [20], [21].

Loss of protective sensation resulting

Microbiology

Polymicrobial involvement is the rule in severe diabetic foot infections, whereas mild infections are often monomicrobial. Gram-positive cocci predominate in most infections, but gram-negative rods and anaerobic organisms are also frequently isolated from deeper or limb-threatening infections [7], [21], [35], [36], [37], [38], [39], [40]. In the latter circumstances, 3 to 5 organisms can often be cultured. As indicated, the most common organisms cultured are the aerobic gram-positive cocci. The

Clinical presentation (classification)

Foot infection in diabetic patients is most frequently a sequela to neuropathic or neuroischemic foot ulceration [6], [7], [12], [20], [38]. The open lesion allows entry of microbes that flourish in the presence of an impaired host response [1], [38], [53]. In patients with vascular insufficiency, the infection rapidly progresses and can quickly evolve into a limb- or life-threatening situation. Because of the neuropathic patients' loss of protective sensation, the emergent nature of an

Management

The severity of the infection, medical status of the patient, and history of medication allergies will usually guide antibiotic therapy [6], [7], [38], [55]. Initial antimicrobial treatment of diabetic foot infections therefore requires careful consideration of these factors in concert with an understanding of antibiotic spectrums of activity, toxicities, and interactions. Once definitive reliable cultures are reported, initial antibiotic regimens should be revised to narrow the coverage to

Treatment of non–limb-threatening infections

These relatively mild infections are often associated with superficial ulcers and can usually be managed without hospitalization. Persons with underlying critical ischemia or deep infection should not be considered in this category. Most non–limb-threatening infections are primarily monomicrobial, with aerobic gram-positive cocci, such as S aureus, Staphylococcus epidermidis, and streptococci (including enterococci) predominating [39], [63], [67], [68]. Nevertheless, gram-negative organisms can

Treatment of limb-threatening infections

Severe, limb-threatening infections include those with ≥2 cm of cellulitis, lymphangitis, deep ulceration or abscess, necrosis, gangrene, osteomyelitis, or critical ischemia [35], [53], [66], [67]. These patients require immediate hospitalization for surgical drainage, metabolic control, and parenteral antibiotic therapy [12], [19], [66], [73]. Fever or systemic signs of infection, including leukocytosis, may not be present in up to 50% of cases because of diabetes-related immunosuppression [12]

Management of osteomyelitis

Osteomyelitis is frequently associated with moderate to severe diabetic foot infections and complicates management [12], [37], [84], [85], [107]. In a series of 2,000 foot infections, Calhoun and Mader [107] noted that osteomyelitis was the most common clinical presentation. In a report of an antibiotic clinical trial for diabetic foot infections, 59 of 96 patients (61%) had underlying osteomyelitis [37]. An earlier study by Newman et al [89] found that osteomyelitis was present in 68% of the

Summary

Management of diabetic foot infections requires a thorough knowledge of the multiple factors involved, including the relevant microbiological characteristics of these infections. Equally important, the practitioner must maintain a current understanding of appropriate diagnostic and treatment protocols. Because no one specific antibiotic regimen will always be appropriate, management of the infected diabetic foot usually requires a combination of therapies. Typically, these include a variety of

References (115)

  • B.A. Lipsky

    Evidence-based antibiotic therapy of diabetic foot infections

    FEMS Immunol Med Microbiol

    (1999)
  • D.L. Steed

    Foundations of good ulcer care

    Am J Surg

    (1998)
  • P.A. Blume et al.

    Diagnosis of pedal osteomyelitis with Tc-99m HMPAO labeled leukocytes

    J Foot Ankle Surg

    (1997)
  • C.J. Palestro et al.

    Rapid diagnosis of pedal osteomyelitis in diabetics with a technetium-99m-labeled monoclonal antigranulocyte antibody

    J Foot Ankle Surg

    (2003)
  • W.B. Morrison et al.

    Work-up of the diabetic foot

    Radiol Clin North Am

    (2002)
  • S.D. Croll et al.

    Role of magnetic resonance imaging in the diagnosis of osteomyelitis in diabetic foot infection

    J Vasc Surg

    (1996)
  • R.M. Bridges et al.

    Diabetic foot infectionspathophysiology and treatment

    Surg Clin North Am

    (1994)
  • Gibbons GW, Eliopoulos GM. Infection of the diabetic foot. In: Kozak GP, Campbell DR, Frykberg RG, Habershaw GM, eds....
  • Reiber GE. Epidemiology of foot ulcers and amputations in the diabetic foot. In: Bowker JH, Pfeifer MA, eds. Levin and...
  • G.E. Reiber et al.

    Causal pathways for incident lower-extremity ulcers in patients with diabetes from two settings

    Diabetes Care

    (1999)
  • R.E. Pecoraro et al.

    Pathways to diabetic limb amputation; basis for prevention

    Diabetes Care

    (1990)
  • R.G. Frykberg

    Diabetic foot ulcerspathogenesis and management

    Am Fam Physician

    (2002)
  • R.G. Frykberg et al.

    Diabetic foot disorders; a clinical practice guideline

    J Foot Ankle Surg

    (2000)
  • S.D. Ramsey et al.

    Incidence, outcomes, and cost of foot ulcers in patients with diabetes

    Diabetes Care

    (1999)
  • Centers for Disease Control and Prevention. Diabetes surveillance, 1999. US Department of Health and Human Services....
  • American Diabetes Association. Facts and figures. Available at: http://www.diabetes.org/main/info/facts/facts.jsp....
  • American Diabetes Association. Diabetes 1993 vital statistics. Alexandria, VA: American Diabetes Association,...
  • M. Eneroth et al.

    Clinical characteristics and outcome in 223 diabetic patients with deep foot infections

    Foot Ankle Int

    (1997)
  • A.I. Adler et al.

    Lower-extremity amputation in diabetesthe independent effects of peripheral vascular disease, sensory neuropathy, and foot ulcers

    Diabetes Care

    (1999)
  • G.E. Reiber et al.

    Risk factors for amputation in patients with diabetes mellitus

    Ann Intern Med

    (1992)
  • Boyko EJ, Lipsky BA. Infection and diabetes. In: Harris MI, Cowie C, Stern MP, editors. Diabetes in America, 2nd ed....
  • J.L. Wheat

    Infection and diabetes mellitus

    Diabetes Care

    (1980)
  • B.R. Shah et al.

    Quantifying the risk of infectious diseases for people with diabetes

    Diabetes Care

    (2003)
  • G.M. Caputo et al.

    Assessment and management of foot disease in patients with diabetes

    N Engl J Med

    (1994)
  • E.J. Boyko et al.

    A prospective study of risk factors for diabetic foot ulcerthe Seattle Diabetic Foot Study

    Diabetes Care

    (1999)
  • C.A. Abbott et al.

    The North-West Diabetes Foot Care Studyincidence of, and risk factors for, new diabetic foot ulceration in a community-based patient cohort

    Diabet Med

    (2002)
  • R.G. Frykberg et al.

    Role of neuropathy and high foot pressures in diabetic foot ulceration

    Diabetes Care

    (1998)
  • A.J.M. Boulton et al.

    Pathogenesis of diabetic foot ulceration and measurements of neuropathy

    Wounds

    (2000)
  • P.E. Holstein et al.

    Limb salvage experience in a multidisciplinary diabetic foot unit

    Diabetes Care

    (1999)
  • F.W. LoGerfo et al.

    Vascular and microvascular disease of the foot in diabetes—implications for foot care

    N Engl J Med

    (1984)
  • J.D. Bagdade et al.

    Impaired leukocyte function in patients with poorly controlled diabetes

    Diabetes

    (1974)
  • M. Delamaire et al.

    Impaired leukocyte functions in diabetic patients

    Diabet Med

    (1997)
  • D.G. Armstrong et al.

    Value of white blood cell count with differential in the acute diabetic foot infection

    J Am Podiatr Med Assoc

    (1996)
  • T. Kastenbauer et al.

    Evaluation of granulocyte-colony stimulating factor (Filgrastim) in infected diabetic foot ulcers

    Diabetologia

    (2003)
  • A.W. Karchmer et al.

    Foot infections in diabetesevaluation and management

    Curr Clin Topics Infect Dis

    (1994)
  • J.H. Calhoun et al.

    Treatment of diabetic foot infectionsWagner classification, therapy, and outcome

    Foot Ankle

    (1988)
  • M.L. Grayson et al.

    Use of ampicillin/sulbactam versus imepenem/cilistatin in the treatment of limb-threatening foot infections in diabetic patients

    Clin Infect Dis

    (1994)
  • Lipsky BA. Infectious problems of the foot in diabetic patients. In: Bowker JH, Pfeifer MA, eds. Levin and O'Neal's The...
  • Lipsky BA, Itani K, Norden C. Linezolid versus ampicillin-sulbactam/amoxicillin-clavulanate for treatment of diabetic...
  • K.S. Scher et al.

    The septic foot in patients with diabetes

    Surgery

    (1988)

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