Diabetic foot medical therapy

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alonso Alvarado, M.D. [2], Vishnu Vardhan Serla M.B.B.S. [3]

Overview

Foot ulcers in diabetes require multidisciplinary assessment, usually by diabetes specialists and surgeons. Treatment consists of appropriate bandages, antibiotics (against staphylococcus, streptococcus and anaerobe strains), debridement and arterial revascularisation. It is often 500 mg to 1000 mg of flucloxacillin, 1 g of amoxicillin and also metronidazole to tackle the putrid smelling bacteria. Specialists are investigating the role of nitric oxide in diabetic wound healing. Nitric oxide is a powerful vasodilator, which helps to bring nutrients to the oxygen deficient wound beds. Specialists are using forms of light therapy such as LLLT to treat diabetic ulcers.

Diabetic Foot Infection Adapted from Diabetes Care. 2013;36(9):2862-71. and Clin Infect Dis. 2012;54(12):e132-73.

Principles of Therapy

• Diabetic foot infection (DFI) is diagnosed clinically by the presence of at least two signs or symptoms of inflammation:

• Local swelling or induration
• Erythema
• Local tenderness or pain
• Local warmth
• Purulent discharge (thick, opaque to white or sanguineous secretion)

• Hospitalization is appropriate for the following conditions:

• Severe (grade 4) infections
• Moderate (grade 3) infections with complicating features

• Severe peripheral arterial disease or limb ischemia
• Lack of home support

• Patients unable to comply with the required outpatient treatment regimen for psychological or social reasons
• Patients not responding to outpatient treatment

• Properly obtained specimens for culture prior to initiating empiric antibiotic therapy provide useful information for guiding antibiotic therapy, particularly in those with chronic or previously treated infections which are commonly caused by obligate anaerobic organisms.

• Infected wounds should be cultured by obtaining tissue samples during any surgical procedure or by tissue biopsy or wound base curettage.
• Bone cultures are optimal for detecting the pathogen in osteomyelitis, but blood cultures are only necessary for those with a severe (grade 4) infection.
• Cultures may be unnecessary for mild infections in patients who have not recently received antibiotic therapy and who are at low risk for methicillin-resistant Staphylococcus aureus (MRSA) infection; these infections are predictably caused solely by staphylococci and streptococci.
• Cultures may yield organisms that are commonly considered to be contaminants (eg, coagulase-negative staphylococci, corynebacteria), but these may be true pathogens in DFIs and are often resistant to the empiric antibiotics.

• Conditions to request consultation from specialists:

• Urgent surgical intervention should be sought for DFIs accompanied by gas in the deeper tissues, an abscess, or necrotizing fasciitis, and less urgent surgery for DFIs with substantial nonviable tissue or extensive bone or joint involvement.
• Consult a vascular surgeon to consider revascularization if ischemia complicates a DFI.
• Infectious diseases specialists should be consulted when cultures yield multiple or antibiotic-resistant organisms, the patient has substantial renal impairment, or the infection does not respond to appropriate medical or surgical therapy in a timely manner.

• No adjunctive therapy has been proven to improve resolution of infection, but for selected diabetic foot wounds that are slow to heal, clinicians might consider using bioengineered skin equivalents, growth factors, granulocyte colony-stimulating factors, hyperbaric oxygen therapy, or negative pressure wound therapy.

Antibiotic Therapy

• Clinically uninfected wounds should not be treated with antibiotic therapy. For all infected wounds, antibiotic therapy combined with appropriate wound care is recommended.

• For clinically infected wounds, consider the questions below:

1. Is there high risk of MRSA?

• Methicillin-resistant Staphylococcus auerus (MRSA) coverage should be considered in the following conditions:

• Prior history of MRSA infection or colonization within the past year
• High local prevalence of MRSA infection or colonization (50% for a mild and 30% for a moderate soft tissue infection)
• Clinically severe diabetic foot infection

2. Has patient received antibiotics in the past month?

• If so, include agents active against gram-negative bacilli in regimen.
• If not, agents targeted against just aerobic gram-positive cocci may be sufficient.

3. Are there risk factors for infection with Pseudomonas aeruginosa or extended-spectrum β-lactamase (ESBL)–producing organisms?

• Anti-pseudomonal agent is usually unnecessary except for patients with risk factors:

• High local prevalence of Pseudomonas aeruginosa infection
• Frequent exposure of the foot to water
• Warm climate

• Coverage of ESBL-producing gram-negative organisms should be considered in countries in which they are relatively common.

4. What is the infection severity status?

• DFI is classified based on its severity according to the Infectious Diseases Society of America (IDSA) guideline or the PEDIS grade developed by International Working Group on the Diabetic Foot (IWGDF). [see Table below]
• Selection of empiric antimicrobial regimen should be determined by the severity of DFI and the likely etiologic agents.

• Mild (grade 2) to moderate (grade 3) DFI without recent antibiotic treatment:

• Highly bioavailable oral antibiotics against aerobic gram-positive cocci may be sufficient.

• Severe (grade 4) DFI:

• Broad-spectrum antibiotics are recommended while culture results and susceptibility data are pending.

Clinical Manifestation PEDIS Grade IDSA Severity No symptoms or signs of infection 1 Uninfected Local infection involving only the skin and the subcutaneous tissue without involvement of deeper tissues and without signs of SIRS If erythema, must be >0.5 cm to ≤2 cm around the ulcer. Exclude other causes of an inflammatory response of the skin (eg, trauma, gout, acute Charcot neuro-osteoarthropathy, fracture, thrombosis, venous stasis). 2 Mild Local infection with erythema >2 cm or involving structures deeper than skin and subcutaneous tissues (eg, abscess, osteomyelitis, septic arthritis, fasciitis) without signs of SIRS 3 Moderate Local infection with the signs of SIRS, as manifested by ≥2 of the following: Temperature >38 °C or <36 °C Heart rate >90 beats/min Respiratory rate >20 breaths/min or PaCO2 <32 mm Hg White blood cell count >12,000 or <4,000 cells/μL or ≥10% immature (band) forms 4 Severe

5. What is the appropriate route, setting, and duration of antibiotic therapy?

Site of Infection, by Severity or Extent Route of Administration Setting Duration of Therapy Soft-tissue only Mild Oral (or topical for superficial infections) Outpatient 1–2 wk; may extend to 4 wk Moderate Oral (or initial parenteral) Outpatient (or inpatient) 1–3 wk Severe Initial parenteral, switch to oral when possible Inpatient, then outpatient 2–4 wk Bone or joint No residual infected tissue Parenteral or oral Inpatient, then outpatient 2–5 d Residual infected soft tissue Parenteral or oral Inpatient, then outpatient 1–3 wk Residual infected, viable bone Initial parenteral, switch to oral when possible Inpatient, then outpatient 4–6 wk Residual dead bone or no surgery Initial parenteral, switch to oral when possible Inpatient, then outpatient ≥3 mo

Empiric Therapy

▸ Click on the following categories to expand treatment regimens.

Mild     High suspicion of MRSA   ▸  Low suspicion of MRSA     Moderate   ▸  High suspicion of MRSA   ▸  Low suspicion of MRSA   ▸  High suspicion of P. aureuginosa     Severe   ▸  Broad-spectrum regimen

High suspicion of MRSA ▸ Doxycycline 100 mg PO q12h OR ▸ TMP/SMZ Low suspicion of MRSA Preferred Regimen ▸ Dicloxacillin 250 mg PO q6h OR ▸ Cephalexin 500mg PO q12h OR ▸ Amoxicillin-clavulanic acid 850/125 mg PO q12h OR ▸ Clindamycin 300-450 mg PO q6h High suspicion of MRSA Preferred Regimen High suspicion of MRSA ▸ Linezolid OR ▸ Daptomycin OR ▸ Vancomycin Low suspicion of MRSA Preferred Regimen ▸ Levofloxacin' OR ▸ Moxifloxacin OR ▸ cefoxitin OR ▸ Ceftriaxone OR ▸ Tigecylin OR ▸ Imipenem-cilastatin High suspicion of P. aureuginosa Preferred Regimen ▸ Piperacilin-tazobactam 'Broad-spectrum regimen Preferred Regimen ▸ Vancomycin PLUS ▸ Ceftazidime OR ▸ Cefepime OR ▸ Piperacillin-Tazobactam OR ▸ Aztreonam OR ▸ [[