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Overview of diabetic foot infections

Masood Ziaee ,MD

Des ,11, 2008

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FOOT ULCERS IN DIABETES

“Rule of 15” 15% of diabetes patients Foot ulcer in lifetime

15% of foot ulcers Osteomyelitis

15% of foot ulcers Amputation

Clinical Care of the Diabetic Foot, 2005

©2006. American College of Physicians. All Rights Reserved.

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INTRODUCTION

Important factors for development of diabetic foot infections include

1. Neuropathy

2. Peripheral vascular disease

3. Hyperglycemia.

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INTRODUCTION (Neuropathy)

Autonomic neuropathy can cause diminished sweat secretion resulting in dry, cracked skin, facilitating microorganism entry.

Motor neuropathy can lead to foot deformities.

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INTRODUCTION

Peripheral arterial disease can lead to impaired blood supply needed for healing of ulcers and infections.

Hyperglycemia impairs neutrophil function and reduces host defenses.

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MICROBIOLOGY 

 Most diabetic foot infections are polymicrobial, with up to five or seven different specific organisms involved.

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MICROBIOLOGY 

Superficial diabetic foot infections are likely to be due to Aerobic gram-positive cocci :

S. aureus, S. agalactiae, S. pyogenes, and coagulase-negative staphylococci

Methicillin-resistant S. aureus should be presumed and empiric antibiotic treatment should include activity against this organism, particularly for patients who are severely ill at the time of presentation.

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MICROBIOLOGY 

Ulcers that are deep, chronically infected, and/or previously treated with antibiotics are more likely to be polymicrobial.

Such wounds may involve the above organisms in addition to Enterococci, Enterobacteriaceae, Pseudomonas Aeruginosa, and Anaerobes.

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MICROBIOLOGY 

Wounds with extensive local inflammation, necrosis, or gangrene with signs of systemic toxicity should be presumed to have anaerobic organisms in addition to the above pathogens.

Potential pathogens include anaerobic streptococci,

Bacteroides species, and Clostridium species.

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CLASSIFICATION (Wagner )

Grade 0 — No ulcer in a high risk foot. Grade 1 — Superficial ulcer involving the full skin thickness but

not underlying tissues.

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CLASSIFICATION (Wagner )

Grade 2 — Deep ulcer, penetrating down to ligaments and muscle, but no bone involvement or abscess formation.

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CLASSIFICATION (Wagner )

Grade 3 — Deep ulcer with cellulitis or abscess formation, often with osteomyelitis.

Grade 4 — Localized gangrene. Grade 5 — Extensive gangrene involving the whole foot.

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DIAGNOSIS

Made on the basis of clinical manifestations :1. Erythema

2. Warmth

3. Tenderness

4. Swelling are observed

5. Pus is grossly visible at an ulcer site or sinus tract.

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Laboratory evaluation

Laboratory evaluation should include :

1. CBC

2. BS

3. Electrolytes

4. ESR

5. CRP

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Laboratory evaluation

Organisms cultured from superficial swabs are not reliable for predicting the pathogens responsible for deeper infection.

Deep tissue cultures are required; for evaluation of osteomyelitis, bone biopsy is needed.

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Laboratory evaluation

Risk for osteomyelitis 

 Evaluation for osteomyelitis is an important consideration in the management of diabetic foot infections.

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Factors increase the likelihood of osteomyelitis

Grossly visible bone or ability to probe to bone

Ulcer size larger than 2 x 2 cm Ulcer depth >3 mm Ulcer duration longer than 1 to 2 weeks ESR >70 mm/h

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Evaluation for osteomyelitis

Patients with diabetic foot infections should have initial evaluation with conventional radiographs.

Those with one or more of the above factors whose radiographs are indeterminate for osteomyelitis should undergo magnetic resonance imaging (MRI).

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The following concepts may help guide radiographic modality selection

1. If the patient is diabetic and has symptoms referable to the foot, MRI is the test of choice.

2. If the patient has symptoms referable to the spine, MRI is the test of choice to evaluate for vertebral osteomyelitis.

3. If MRI is not available, CT is the alternative test of choice.

4. If metal hardware precludes MRI or CT, a nuclear study is the test of choice.

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Osteomyelitis

Evidence of osteomyelitis by these imaging modalities should prompt a bone biopsy to confirm the diagnosis and to guide antimicrobial therapy.

In the absence of osteomyelitis by these alternative imaging modalities, osteomyelitis is unlikely.

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MANAGEMENT 

Management of diabetic foot infections requires

1. Attentive wound management

2. Good nutrition

3. Antimicrobial therapy

4. Glycemic control

5. Fluid and electrolyte balance.

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CLASSIFICATION OF INFECTION

Mild infection Moderate infection Severe infection

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Mild infection

Presence of 2 manifestations of 1. Inflammation (purulence, or erythema, pain,

tenderness, warmth, or induration),

2. Any Cellulitis/erythema extends 2 cm around the ulcer,

3. Infection is limited to the skin or superficial subcutaneous tissues

4. No other local complications or systemic illness.

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Mild infection

1. Treated with outpatient oral antimicrobial therapy.

2. Empiric therapy include activity against skin flora including streptococci and methicillin-resistant S. aureus (MRSA).

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Oral agents for empiric treatment of mild to moderate diabetic foot infections

Regimens with activity against streptococci and MRSA

1-Clindamycin

2-Linezolid

3-Penicillin + Trimethoprim-sulfamethoxazole or doxycycline

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Mild infection 

3.Patients who fail to respond to treatment with agents active against streptococci and MRSA should receive extended antimicrobial coverage to include activity against aerobic gram negative bacilli and anaerobes.

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Oral agents for empiric treatment of mild to moderate diabetic foot infections

Regimens with activity against streptococci, MRSA, aerobic

gram negative bacilli and anaerobes

Trimethoprim-sulfamethoxazole +Amoxicillin-clavulanate

Clindamycin+Ciprofloxacin or levofloxacin or moxifloxacin

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Antibiotic dosing

Clindamycin 300 to 450 mg every 6 to 8 hours

Linezolid 600 mg every 12 hours

Penicillin 500 mg every 6 hours

Trimethoprim-sulfamethoxazole 2 double strength tablets every 12 hours

Doxycycline 100 mg orally every 12 hours

Amoxicillin-clavulanate 2000/125 mg every 12 hours

Ciprofloxacin 750 mg every 12 hours

Levofloxacin 750 mg every 24 hours

Moxifloxacin 400 mg every 24 hours

Oral agents for empiric treatment of mild to moderate diabetic foot infections

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Mild infection 

4.If infection in a clinically stable patient fails to respond to more than one antibiotic course, some favor discontinuing antimicrobial therapy to optimize the yield of culture specimens obtained a few days later .

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Duration of therapy

Oral antibiotic therapy in conjunction with attentive wound care until there is evidence that the infection has resolved (usually about 1 to 2 weeks).

Antibiotics need not be administered for the entire duration that the wound remains open.

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Moderate infection

Infection in a patient who is1. Systemically well and metabolically stable

2. Which has 1 of the following characteristics: cellulitis extending >2 cm, lymphangitic streaking, spread beneath the superficial fascia, deep-tissue abscess, gangrene, and involvement of muscle, tendon, joint or bone.

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Moderate infection

 Empiric therapy of deep ulcers with extension to fascia should include activity against streptococci, MRSA, aerobic gram negative bacilli and anaerobes.

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Parenteral agents for empiric treatment of moderate to severe diabetic foot infections

Vancomycin +regimens active against aerobic gram negative bacilli and anaerobes:

Beta-lactam/beta-lactamase inhibitors

Ampicillin-sulbactam 3 g every 6 hours

Piperacillin/tazobactam 4.5 g every 8 hours

Ticarcillin-clavulanate 3.1 g every 4 hours

Carbapenems

Imipenem 500 mg every 6 hours

Meropenem 1 g every 8 hours

Alternative regimens

Metronidazole PLUS one of the following : 500 mg IV every 8 hours

Ceftazidime 2 g every 8 to 12 hours

Cefepime 2 g every 12 hours

Ciprofloxacin 400 mg IV every 12 hours

Aztreonam 2 g every 6 to 8 hours

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Duration of therapy

1. Patients with infection also requiring surgical debridement should receive intravenous antibiotic therapy perioperatively.

2. In the absence of osteomyelitis, antibiotic therapy should be administered in conjunction with attentive wound care until signs of infection appear to have resolved (2 to 4 weeks of therapy is usually sufficient).

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Duration of therapy

3.If there is a good response to parenteral therapy, oral agents can be used to complete the course of treatment.

4.If clinical evidence of infection persists beyond the expected duration, consider issues of patient adherence to therapy, development of antibiotic resistance, an undiagnosed deep abscess, or ischemia

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Severe infection

Infection in a patient with Limb threatening diabetic foot infections.

Systemic toxicity or metabolic instability (eg, fever, chills, tachycardia, hypotension, confusion, vomiting, leukocytosis, acidosis, severe hyperglycemia, or azotemia).

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Severe infection

 Limb threatening diabetic foot infections should be treated with parenteral antibiotic therapy and, in most cases, surgical debridement.

Empiric therapy should include activity against streptococci, MRSA, aerobic gram negative bacilli and anaerobes.

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Duration of therapy

Patients requiring amputation of the involved limb should receive intravenous antibiotic therapy perioperatively.

If the entire area of infection is fully resected, a brief course of oral antibiotic therapy (about a week) following surgery is usually sufficient

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Duration of therapy

Duration of antibiotic therapy in the setting of osteomyelitis

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Antibiotic therapy for osteomyelitis

 Infectious agent

Antibiotic Dosing

MSSA 

Nafcillin 1-2 g intravenously every 6 hours

Oxacillin 1-2 g intravenously every 6 hours

Cefazolin 1 g intravenously every 8 hours

MRSA* Vancomycin

30 mg/kg intravenously every 24 hours in 2 equally divided doses; not to exceed 2 g/24 hours unless concentrations in serum are inappropriately low

Coagulase negative staphylococci Vancomycin

30 mg/kg intravenously every 24 hours in 2 equally divided doses; not to exceed 2 g/24 hours unless concentrations in serum are inappropriately low

Gram negative organisms (including Pseudomonas)

Ciprofloxacin 750 mg orally twice daily

Levofloxacin 750 mg orally once daily

Ceftazidime 2g intravenously every 8 hours

Cefepime 2 g intravenously every 12 hours

Empiric therapy Vancomycin PLUS an agent with activity against gram negative organisms

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Duration of therapy in osteomyelitis

Bony ablation with no residual infected soft tissue

24-72 hrs

Bony ablation with residual infected soft tissue

2-4 wks

Non-ablative bony resection back to viable but potentially or definitely infected bone

4-6 wks

Retained dead bone min 3 months

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Duration of therapy

Mild infection : 1-2 weeks Moderate infection : 2 to 4 weeks, unless

osteomyelitis Severe infection : soft tissue up to 4 weeks

unless osteomyelitis Osteomyelitis: depends on degree of resection

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Adjunctive therapies

Adjunctive therapies for treatment of diabetic foot infections include

1. Vacuum assisted wound closure

2. Hyperbaric oxygen

3. Granulocyte colony-stimulating factor (G-CSF).

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Reference

November 2008

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