Dr. Gujral's Speciality Clinics

Diabetic Foot Infections

Background: Foot infections are the most common problems in persons with diabetes. These individuals are predisposed to foot infections because of a compromised vascular supply secondary to diabetes. Local trauma and/or pressure (often in association with lack of sensation because of neuropathy), in addition to microvascular disease, may result in a variety of diabetic foot infections.

The spectrum of foot infections in diabetes ranges from simple superficial cellulitis to chronic osteomyelitis. Infections in patients with diabetes are difficult to treat because these patients have impaired microvascular circulation, which limits the access of phagocytic cells to the infected area and results in a poor concentration of antibiotics in the infected tissues. For this reason, cellulitis is the most easily treatable and reversible form of foot infections in patients with diabetes. Deep skin and soft tissue infections also usually are curable, but they can be life threatening and result in substantial long-term morbidity.

In terms of the infecting microorganisms and the likelihood of successful treatment with antimicrobial therapy, acute osteomyelitis in people with diabetes is essentially the same as in those without diabetes. Chronic osteomyelitis in patients with diabetes mellitus is the most difficult infection to cure. Adequate surgical debridement, in addition to antimicrobial therapy, is necessary to cure chronic osteomyelitis.

Patients with diabetes also can have a combined infection involving bone and soft tissue called fetid foot. This extensive soft tissue and bone infection causes a foul exudate, is chronic, and usually requires extensive surgical debridement and/or amputation.

Individuals with diabetes also may have peripheral vascular disease that involves the large vessels, in addition to microvascular and capillary disease that results in peripheral vascular disease with gangrene. Dry gangrene usually is managed with expectant care, and gross infection usually is not present. Wet gangrene usually has an infectious component and requires surgical debridement and/or antimicrobial therapy to control the infection.

Except for chronic osteomyelitis, infections in patients with diabetes are caused by the same microorganisms that can infect the extremities of those without diabetes. Gas gangrene is conspicuous because of its low incidence in patients with diabetes, but deep skin and soft tissue infections, which are due to gas-producing organisms, frequently occur in patients with diabetes. In general, people with diabetes have infections that are more severe and take longer to cure than equivalent infections in other people.

Pathophysiology: Diabetes mellitus is a disorder that primarily affects the microvascular circulation. In the extremities, microvascular disease due to "sugar-coated capillaries" limits the blood supply to the superficial and deep structures. Pressure due to ill-fitting shoes or trauma further compromises the local blood supply at the microvascular level, predisposing the patient to infection. The infection may involve the skin, soft tissues, bone, or all of these tissues.

Diabetes also accelerates macrovascular disease, which is evident clinically as accelerating atherosclerosis and/or peripheral vascular disease. Most diabetic foot infections occur in the setting of good dorsalis pedis pulses; this finding indicates that the primary problem in diabetic foot infections is microvascular compromise. Impaired microvascular circulation hinders white cell migration into the area of infection and limits the ability of antibiotics to reach the site of infection in an effective concentration. Diabetic neuropathy may be encountered in conjunction with vasculopathy. This may allow for incidental trauma that goes unrecognized (eg, blistering, penetrating foreign body).

In chronic osteomyelitis, a sequestrum and involucrum form; these represent islands of infected bone. Bone fragments that are isolated have no blood supply. Administered antibiotics do not penetrate the devascularized infected bone fragments; they can enter the area of osteomyelitis only via the remaining blood supply. Therefore, antibiotic therapy alone cannot cure patients with chronic osteomyelitis without surgical debridement to remove these isolated infected elements. Surgical debridement is essential to remove the infected bony fragments that the antibiotics cannot reach so that affected areas can be treated with antimicrobial therapy.

Frequency:

Internationally: Diabetic foot infections range from cellulitis to chronic osteomyelitis, and, globally, they are the most common skeletal and soft tissue infections in patients with diabetes.

Mortality/Morbidity: Mortality is not common, except in unusual circumstances. The mortality risk is highest in patients with chronic osteomyelitis and in those with acute necrotizing soft tissue infections.

Race: The incidence of diabetic foot infections is similar to that of diabetes in various ethnic groups.

Sex: No important sex differences exist.

Age: Diabetic foot infections most frequently affect elderly patients.

History: Patients may or may not have a history of trauma or previous infection.

Physical: Findings after physical examination may include the following:

Cellulitis

Cellulitis may involve tender and erythematous non�raised skin lesions on the lower extremity that may or may not be accompanied by lymphangitis.

Lymphangitis suggests a group A streptococcal etiology.

If bullae are present, Staphylococcus aureus is the most likely pathogen, but group A streptococci occasionally may cause bullous lesions.

No ulcer or wound exudate is present in patients with cellulitis.

Deep skin and soft tissue infections

Patients with deep skin and soft tissue infections may be acutely ill, with painful induration of the soft tissues in the extremity.

These infections are particularly common in the thigh area, but they may be seen anywhere on the leg or foot.

Wound discharge usually is not present. In mixed infections that may involve anaerobes, crepitation may be noted over the afflicted area.

Extreme pain and tenderness indicate the possibility of a compartment syndrome, which may be diagnosed with the aid of a CT scan. Similarly, extreme pain may be an indication of infection with clostridial species (ie, gas gangrene).

The tissues are not tense, and bullae may be present.

If a discharge is present, it often is foul.

Acute osteomyelitis

Unless peripheral neuropathy is present, the patient has pain at the site of the involved bone.

Usually, fever and regional adenopathy are absent.

Chronic osteomyelitis

In chronic osteomyelitis, the patient’s temperature usually is less than 102�F.

Discharge is not uncommonly foul.

No lymphangitis is observed.

Pain may or may not be present, depending on the degree of peripheral neuropathy.
The deep penetrating ulcers and sinuses usually are located between the toes or on the plantar surface of the foot.
In patients with diabetes, chronic osteomyelitis usually does not occur on the medial malleoli, shins, or heels.
Importantly, deep penetrating foot ulcers or deep sinus tracts are diagnostic of chronic osteomyelitis.

Causes: The microbiologic features of diabetic foot infections vary according to the tissue infected.

In patients with diabetes, superficial skin infections such as cellulitis are caused by the same organisms as those in healthy hosts, namely group A streptococci and S aureus. However, in unusual epidemiologic circumstances, organisms such as Pasteurella multocida (eg, from dog or cat bites or scratches) may be noted and should always be considered.

Group B streptococcal cellulitis is uncommon in healthy hosts and not uncommon in patients with diabetes. In people with diabetes, group B streptococci may cause urinary tract infections and catheter-associated bacteriuria in addition to cellulitis, skin and/or soft tissue infections, and chronic osteomyelitis. Such infections may be complicated by bacteremia.

In patients with diabetes, deep soft tissue infections can be associated with gas-producing gram-negative bacilli. Clinically, these infections appear as necrotizing fasciitis, compartment syndrome, or myositis. Gas gangrene is uncommon in persons with diabetes.

Acute osteomyelitis usually occurs as a result of foot trauma in an individual with diabetes. The distribution of organisms is the same as in an individual without diabetes who has acute osteomyelitis.

In chronic osteomyelitis, the pathogens are group A and group B streptococci, aerobic gram-negative bacilli, and Bacteroides fragilis, among others.

Pseudomonas aeruginosa generally is not a pathogen in chronic osteomyelitis in patients with diabetes.

P aeruginosa frequently is cultured from samples obtained from a draining sinus tract or deep penetrating ulcers in patients with diabetes. However, these organisms are superficial colonizers and generally are not the cause of the bone infection.

Because Pseudomonas organisms are water-borne, superficial ulcers may be contaminated by bacteria in wet socks or dressings. To the author’s knowledge, no well-documented cases of biopsy-proven P aeruginosa infection have been reported in patients with chronic osteomyelitis.

Bone biopsy performed under aseptic conditions in the operating room reveals that chronic osteomyelitis in patients with diabetes is not due to P aeruginosa.

B fragilis is an important bone pathogen in chronic osteomyelitis in patients with diabetes.

Other pathogens implicated in chronic osteomyelitis in patients with diabetes include Escherichia coli, Proteus mirabilis, and Klebsiella pneumoniae.

Fetid foot represents a combined deep skin and soft tissue infection caused by pathogens involved in chronic osteomyelitis.

Other Problems to be Considered:

Cellulitis - Leukoclastic angitis, diabetic dermopathy, chronic venostatic change, superficial thrombophlebitis

Deep skin and soft tissue infections - Gas gangrene, synergistic gangrene, Vibrio vulnificus infection, Aeromonas hydrophilia infection

Acute osteomyelitis - Sickle cell crisis, Lyme arthritis, sarcoid arthritis, blunt bone trauma, bone tumor

Chronic osteomyelitis - Squamous cell carcinoma, bone tumor, neuropathic joint

Lab Studies:

Cellulitis

The CBC count and erythrocyte sedimentation rate (ESR) are slightly or moderately elevated in cellulitis. Elevations are not diagnostic and, therefore, are unhelpful.

Blood culture results usually are negative. If positive, they usually indicate the presence of group A or group B streptococci. Cultures of skin via aspiration or biopsy generally are unrewarding.

Skin and soft tissue infections

The CBC count and ESR are mildly or moderately elevated.

If bullae are present, Gram stain and culture results in aspirated exudate from a bullous lesion may provide clues to the etiology of the infection.

Blood culture results may be positive.

Acute osteomyelitis

The CBC count usually reveals a leukocytosis, and the ESR is moderately or highly elevated.

Blood culture results usually are negative. When positive, the findings most frequently indicate the presence of S aureus.

Chronic osteomyelitis

The CBC count often is within the reference range. Usually, the ESR is very highly elevated; it may exceed 100 mm/h.

The platelet count often is elevated in chronic osteomyelitis.

Blood culture results usually are negative in patients with chronic osteomyelitis.

Imaging Studies:

Cellulitis: Image studies are not applicable.

Deep skin and soft tissue infections

In a patient with diabetes considered to have a deep soft tissue infection, plain radiography, CT scan, or MRI may be performed to rule out a compartment syndrome and to demonstrate the presence of gas or a foreign body in the deep tissues.

A finding of excessive gas signifies a mixed aerobic-anaerobic infection in contrast to gas gangrene (clostridial myonecrosis).

Acute osteomyelitis

For long bones, plain radiographic findings generally become abnormal after 10-14 days. Soft tissue swelling and periosteal elevation are the earliest signs of acute osteomyelitis on a plain radiograph.

Bone scan findings are positive within 24 hours in acute osteomyelitis.

A bone scan is preferred to gallium or indium scans in the assessment of acute osteomyelitis.

Gallium or indium scans offer no additional information, and the findings are not more specific than those of bone scans in the diagnosis of osteomyelitis.

Indium scans often show false-negative results in acute or chronic osteomyelitis.

Chronic osteomyelitis

When osteomyelitis becomes chronic, plain radiographic findings invariably are abnormal.

Bone scans usually are unnecessary unless diagnostic confusion exists with another disorder.

A bone tumor is best differentiated from chronic osteomyelitis with the aid of bone scanning or MRI prior to definitive bone biopsy.

Other Tests:

Patients with diabetic foot infections and peripheral vascular disease may benefit from vascular surgical evaluation to bypass large-vessel occlusive disease. However, large-vessel bypass does not cure the microvascular component of diabetic foot infections.

Procedures:

Aspiration of a sample from the leading edge of the erythematous border in a patient with cellulitis usually is not necessary, but a sample may be aspirated if the likely organism must be identified on initial presentation. However, the yield is low, likely to be less than 5%.

Samples from deep skin and soft tissue infections may be aspirated. Gram stains and/or cultures may be used to identify the organism.

Aside from blood culturing, radiography, and nuclear imaging studies, bone biopsy is not necessary in acute osteomyelitis because the pathogens are predictable.

Bone biopsy performed under aseptic conditions in the operating room is the preferred way to identify the causative pathogen in chronic osteomyelitis. Because surgical debridement is critical in treating chronic osteomyelitis, bone biopsy specimens usually are not obtained during the surgical debridement procedure.

Histologic Findings: Involucrum and/or sequestrum may be present in the cortical bone in cases of chronic osteomyelitis. Subperiosteal elevation and/or infection may involve the cortex in acute osteomyelitis.

Staging: Staging is applicable only in cases of chronic osteomyelitis that require surgery.

Medical Care:

Immobilization is important in acute or chronic osteomyelitis.

Surgical Care: Chronic osteomyelitis cannot be cured without adequate surgical debridement.

Consultations:

Appropriate consultation with a surgeon should be obtained for debridement and/or amputation in chronic osteomyelitis.

A general or vascular surgeon should be consulted for the debridement or decompression of compartment syndromes in patients with deep skin and soft tissue infections.

An infectious disease specialist should be consulted in the treatment of all patients with diabetic foot infections to optimize the antimicrobial therapy.

Drug Category: Antibiotics -- Appropriate monotherapy for cellulitis includes cefazolin or clindamycin. Although gram-negative organisms are the unusual causes of cellulitis, even in diabetes, if they are suspected, a fluoroquinolone (eg, levofloxacin) may be used in conjunction with clindamycin.

In patients with diabetes, deep skin and severe soft tissue infections usually are due to mixed aerobic and anaerobic organisms. These infections may be treated with monotherapy involving meropenem or piperacillin and tazobactam. Alternatively, clindamycin plus levofloxacin or metronidazole may be used.

Acute osteomyelitis, which usually is due to S aureus, may be treated with cefazolin, clindamycin, and an antistaphylococcal penicillin (eg, nafcillin).

In chronic osteomyelitis, coverage must be directed against S aureus, group A and group B streptococci, aerobic gram-negative bacilli (excluding P aeruginosa), and B fragilis. Monotherapy for chronic osteomyelitis may include ampicillin and sulbactam, piperacillin and tazobactam, or meropenem. In chronic osteomyelitis, antimicrobial therapy without adequate debridement does not eliminate the infection.

Combination therapy for diabetic foot infections involves levofloxacin plus clindamycin.

Further Inpatient Care:

Surgical debridement in chronic osteomyelitis is the single-most important therapeutic intervention. Chronic osteomyelitis cannot be cured without adequate surgical debridement. In some cases, amputation may be required.

If amputation is performed, physical therapy and rehabilitation may be started on an inpatient basis and completed on an outpatient basis.

Further Outpatient Care:

Cellulitis: No further care is necessary.

Skin and soft tissue infection: Additional debridement generally is indicated. If the foot is involved, the best care plan is aggressive therapy to avoid surgery beyond transmetatarsal amputation, ie, limit surgical extirpation to the forefoot.

Acute osteomyelitis: Monitor the patient’s condition to ensure that the infection has resolved.

Chronic osteomyelitis: Ensure that debridement is complete and that no further remnants of infected bone remain.

In/Out Patient Meds:

Cellulitis, skin and soft tissue infections, acute osteomyelitis, and chronic osteomyelitis may be treated with oral medications in an outpatient setting on a case-by-case basis.

If oral antibiotic therapy with excellent bioavailability is selected, it is equivalent to intravenous therapy. Therefore, home intravenous therapy for osteomyelitis is seldom needed. For virtually all infecting organisms, even those that are highly resistant, numerous oral antibiotics can be used in place of intravenous antibiotics.

In chronic osteomyelitis, neither oral nor intravenous medications are effective without adequate surgical debridement.

Deterrence/Prevention:

Patients with diabetes must be careful to avoid foot trauma and to properly care for their feet to minimize the possibility of infection.

Complications:

Bacteremia may accompany cellulitis, skin or soft tissue infections, and/or acute osteomyelitis, but these are not complications per se.

If chronic osteomyelitis is left untreated for years, it may lead to complications such as amyloidosis or squamous cell carcinoma at the site of drainage through the skin.

Bacteremia and septic shock rarely, if ever, occur as a result of chronic osteomyelitis.

Prognosis:

The prognosis for cases of cellulitis, skin and/or soft tissue infections, or acute osteomyelitis depends on the adequacy of antimicrobial therapy and surgical debridement as indicated.

For cases of chronic osteomyelitis, the prognosis is directly related to the vascular supply in the affected limb and the adequacy of surgical debridement.

Patient Education:

Patients must understand that chronic osteomyelitis cannot be cured with antibiotics alone and that adequate surgical debridement is necessary.

Patients who are unwilling to undergo the surgical procedure must understand the long-term complications of chronic osteomyelitis. Long-term suppressive therapy may decrease the incidence of septic complications, but it does not affect the long-term complications, which may include amyloidosis or squamous cell carcinoma at the drainage site.

Medical/Legal Pitfalls:

Patients with chronic osteomyelitis should be advised that if the infection is not adequately treated with sufficient surgical debridement and/or amputation, systemic complications may occur over time.

Possible systemic complications include bacteremia and/or systemic infection, amyloidosis, and squamous cell carcinoma at the affected site.

Further Reading

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