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2 Overview of diabetic foot infections Masood Ziaee,MD Des,11, 2008

3 FOOT ULCERS IN DIABETES “Rule of 15” 15% of diabetes patientsFoot ulcer in lifetime 15% of foot ulcersOsteomyelitis 15% of foot ulcersAmputation Clinical Care of the Diabetic Foot, 2005 ©2006. American College of Physicians. All Rights Reserved.

4 INTRODUCTION Important factors for development of diabetic foot infections include 1. Neuropathy 2. Peripheral vascular disease 3. Hyperglycemia. ONLINE 16.3

5 INTRODUCTION (Neuropathy) Autonomic neuropathy can cause diminished sweat secretion resulting in dry, cracked skin, facilitating microorganism entry. Motor neuropathy can lead to foot deformities. ONLINE 16.3

6 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. ONLINE 16.3

7 MICROBIOLOGY Most diabetic foot infections are polymicrobial, with up to five or seven different specific organisms involved. ONLINE 16.3

8 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. ONLINE 16.3

9 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. ONLINE 16.3

10 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. ONLINE 16.3

11 CLASSIFICATION (Wagner ) Grade 0 — No ulcer in a high risk foot. Grade 1 — Superficial ulcer involving the full skin thickness but not underlying tissues. ONLINE 16.3

12 CLASSIFICATION (Wagner ) Grade 2 — Deep ulcer, penetrating down to ligaments and muscle, but no bone involvement or abscess formation. ONLINE 16.3

13 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. ONLINE 16.3

14 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. ONLINE 16.3

15 Laboratory evaluation Laboratory evaluation should include : 1. CBC 2. BS 3. Electrolytes 4. ESR 5. CRP ONLINE 16.3

16 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. ONLINE 16.3

17 Laboratory evaluation Risk for osteomyelitis Evaluation for osteomyelitis is an important consideration in the management of diabetic foot infections. ONLINE 16.3

18 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 ONLINE 16.3

19 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). ONLINE 16.3

20 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. ONLINE 16.3

21 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. ONLINE 16.3

22 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. ONLINE 16.3

23 CLASSIFICATION OF INFECTION  Mild infection  Moderate infection  Severe infection

24 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. ONLINE 16.3

25 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). ONLINE 16.3

26 ONLINE 16.3 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

27 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. ONLINE 16.3

28 ONLINE 16.3 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

29 Antibiotic dosing Clindamycin300 to 450 mg every 6 to 8 hours Linezolid600 mg every 12 hours Penicillin500 mg every 6 hours Trimethoprim-sulfamethoxazole2 double strength tablets every 12 hours Doxycycline100 mg orally every 12 hours Amoxicillin-clavulanate2000/125 mg every 12 hours Ciprofloxacin750 mg every 12 hours Levofloxacin750 mg every 24 hours Moxifloxacin400 mg every 24 hours Oral agents for empiric treatment of mild to moderate diabetic foot infections ONLINE 16.3

30 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. ONLINE 16.3

31 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. ONLINE 16.3

32 Moderate infection Infection in a patient who is 1. 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. ONLINE 16.3

33 Moderate infection Empiric therapy of deep ulcers with extension to fascia should include activity against streptococci, MRSA, aerobic gram negative bacilli and anaerobes. ONLINE 16.3

34 ONLINE 16.3 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 3 g every 6 hoursAmpicillin-sulbactam 4.5 g every 8 hoursPiperacillin/tazobactam 3.1 g every 4 hoursTicarcillin-clavulanate Carbapenems 500 mg every 6 hoursImipenem 1 g every 8 hoursMeropenem Alternative regimens 500 mg IV every 8 hoursMetronidazole PLUS one of the following: 2 g every 8 to 12 hoursCeftazidime 2 g every 12 hoursCefepime 400 mg IV every 12 hoursCiprofloxacin 2 g every 6 to 8 hoursAztreonam

35 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). ONLINE 16.3

36 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 ONLINE 16.3

37 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). ONLINE 16.3

38 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. ONLINE 16.3

39 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 ONLINE 16.3

40 Duration of therapy Duration of antibiotic therapy in the setting of osteomyelitis

41 ONLINE 16.3 Antibiotic therapy for osteomyelitis DosingAntibiotic Infectious agent 1-2 g intravenously every 6 hoursNafcillin MSSA 1-2 g intravenously every 6 hoursOxacillin 1 g intravenously every 8 hoursCefazolin 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 Vancomycin MRSA* 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 Vancomycin Coagulase negative staphylococci 750 mg orally twice dailyCiprofloxacin Gram negative organisms (including Pseudomonas) 750 mg orally once dailyLevofloxacin 2g intravenously every 8 hoursCeftazidime 2 g intravenously every 12 hoursCefepime Vancomycin PLUS an agent with activity against gram negative organisms Empiric therapy

42 Duration of therapy in osteomyelitis Bony ablation with no residual infected soft tissue 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

43 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

44 Adjunctive therapies Adjunctive therapies for treatment of diabetic foot infections include 1. Vacuum assisted wound closure 2. Hyperbaric oxygenoxygen 3. Granulocyte colony-stimulating factor (G-CSF). Granulocyte colony-stimulating factor ONLINE 16.3

45 Reference November 2008 ONLINE 16.3

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