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] Anahita Deylamsalehi, M.D.[3]

Overview

Appropriate wound care is essential for the management of all diabetic foot ulcers. Uninfected diabetic ulcers do not require antibiotic therapy. In the contrary for acutely infected wounds, empiric antibiotic therapy with coverage against Gram-positive cocci should be start right after obtaining a post-debridement specimen for aerobic and anaerobic culture. Infections with antibiotic-resistant organisms and those that have chronic or severe ulcers or have been previously treated usually require broader spectrum regimens. Treatment strategies are dependent on ulcer's grade, presence of infection and perfusion. For an effective treatment which lower the chance of the future diabetic foot ulcers control of blood sugar, pressure off-loading and treatment of other comorbidities are also critical. Aim of treatment should be focused on improving prognosis and decreasing complications such as amputation. In very severe ulcers or when the patient has the history of previous MRSA infection or colonization within the past year and in regions with high prevalence of MRSA infection, MRSA should be also covered by antibiotic treatments. For an ideal treatment physicians should evaluate the severity of ulcers and possible risk factors of pseudomonas aeruginosa or extended-spectrum β-lactamase (ESBL)–producing organisms.

Diabetic Foot Ulcer

The Cochrane Collaboration has reviewed hydrocolloids[1], hydrogels[2], and alginates[3].

The International Working Group on the Diabetic Foot (IWGDF) recommends[4]:

  • "Dressings should be selected principally on the basis of exudate control, comfort, and cost"

Hydrocolloids and hydrogels are available as generic bandages.

Diabetic Foot Infection

Principles of Therapy Adapted from Diabetes Care. 2013;36(9):2862-71.[5] and Clin Infect Dis. 2012;54(12):e132-73.[6]


Indications for Hospitalization
Consultation
Adjunctive Therapy

Selection of Antibiotic Regimen

1. Is there high risk of MRSA?
2. Is the infected wound chronic or treated with antibiotics in the past month?
3. Are there risk factors for infection with Pseudomonas aeruginosa or extended-spectrum β-lactamase (ESBL)–producing organisms?
4. What is the severity status?
Clinical Manifestation PEDIS Grade IDSA Severity
Wound lacking purulence or any manifestations of inflammation 1 Uninfected
2 Mild
Infection in a patient who is metabolically stable and systemically well, but with ≥1 of the following characterisitics: 3 Moderate
Infection in a patient with metabolic instability (eg, acidosis, severe hyperglycemia, or azotemia) or systemic toxicity as manifested by ≥2 of the following: 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 (Grade 2) Oral (or topical for superficial infections) Outpatient 1–2 wk
Moderate (Grade 3) Oral (or initial Route of administration|parenteral]]) Outpatient (or inpatient) 1–3 wk
Severe (Grade 4) 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.

    Uninfected (Grade 1)

  ▸  No Evidence of Infection

    Mild (Grade 2)

  ▸  Acute Infection Without Recent Antibiotic Use

  ▸  High Risk for MRSA

    Moderate to Severe (Grade 3–4)

  ▸  Chronic Infection or Recent Antibiotic Use

  ▸  High Risk for MRSA

  ▸  High Risk for Pseudomonas aureuginosa

  ▸  Polymicrobial Infection

Uninfected Wound, No Evidence of Infection
Uninfected wounds should be managed with appropriate wound care.
Antibiotic therapy is not recommended.
Mild DFI, Acute Infection Without Recent Antibiotic Use
Preferred Regimen
Dicloxacillin 125–250 mg PO qid
OR
Clindamycin 150–300 mg PO qid
OR
Cephalexin 500 mg PO qid
OR
Levofloxacin 750 mg PO qd
OR
Amoxicillin-Clavulanate 500 mg PO bid (or 250 mg PO tid)
Usually active against community-associated MRSA, but check macrolide sensitivity and consider ordering a D-test before using for MRSA.
Relatively broad-spectrum oral agent that includes anaerobic coverage.
Mild DFI, High Risk for MRSA
Preferred Regimen
Doxycycline 100 mg PO q12h
OR
TMP–SMX 80-160 mg/400-800 mg PO q12h
Active against many MRSA & some gram-negatives; uncertain against streptococci.
Moderate to Severe DFI, Chronic Infection or Recent Antibiotic Use
Preferred Regimen
Levofloxacin 750 mg IV/PO q24h
OR
Cefoxitin 1 g IV q4h (or 2 g IV q6–8h)
OR
Ceftriaxone 1–2 g/day IV/IM q12–24h
OR
Ampicillin–Sulbactam 1.5–3 g IV/IM q6h
OR
Moxifloxacin 400 mg IV/PO q24h
OR
Ertapenem 1 g IV/IM q24h
OR
Tigecycline 100 mg IV, then 50 mg IV q12h
OR
Imipenem–Cilastatin 0.5–1 g IV q6–8h
Alternative Regimen
Levofloxacin 750 mg IV/PO q24h
OR
Ciprofloxacin 600–1200 mg/day IV q6–12h
OR
Ciprofloxacin 1200–2700 mg IV q6–12h (for more severe cases)
PLUS
Clindamycin 150–300 mg PO qid
Active against MRSA.
Not active against MRSA; consider when ESBL-producing pathogens suspected.
Moderate to Severe DFI, High Risk for MRSA
Preferred Regimen
Linezolid 600 mg IV/PO q12h
OR
Daptomycin 4 mg/kg IV q24h
OR
Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L)
Moderate to Severe DFI, High Risk for Pseudomonas aeruginosa
Preferred Regimen
Piperacillin–Tazobactam 3.375 g IV q6–8h
Moderate to Severe DFI, Polymicrobial Infection
Preferred Regimen
Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L)
OR
Linezolid 600 mg IV/PO q12h
OR
Daptomycin 4 mg/kg IV q24h
PLUS
Piperacillin–Tazobactam 3.375 g IV q6–8h
OR
Imipenem–Cilastatin 0.5–1 g IV q6–8h
OR
Ertapenem 1 g IV/IM q24h
OR
Meropenem 1 g IV q8h
Alternative Regimen
Vancomycin 15–20 mg/kg IV q8–12h (trough: 10–20 mg/L)
OR
Linezolid 600 mg IV/PO q12h
OR
Daptomycin 4 mg/kg IV q24h
PLUS
Ceftazidime 2 g IV q8h
OR
Cefepime 2 g IV q8h
OR
Aztreonam 2 g IV q6–8h
PLUS
Metronidazole 15 mg/kg IV, then 7.5 mg/kg IV q6h


References

  1. Dumville JC, Deshpande S, O'Meara S, Speak K (2013). "Hydrocolloid dressings for healing diabetic foot ulcers". Cochrane Database Syst Rev (8): CD009099. doi:10.1002/14651858.CD009099.pub3. PMC 7111300 Check |pmc= value (help). PMID 23922167.
  2. Dumville JC, O'Meara S, Deshpande S, Speak K (2013). "Hydrogel dressings for healing diabetic foot ulcers". Cochrane Database Syst Rev (7): CD009101. doi:10.1002/14651858.CD009101.pub3. PMC 6486218. PMID 23846869.
  3. Dumville JC, O'Meara S, Deshpande S, Speak K (2013). "Alginate dressings for healing diabetic foot ulcers". Cochrane Database Syst Rev (6): CD009110. doi:10.1002/14651858.CD009110.pub3. PMC 7111427 Check |pmc= value (help). PMID 23799857.
  4. Rayman G, Vas P, Dhatariya K, Driver V, Hartemann A, Londahl M; et al. (2020). "Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes (IWGDF 2019 update)". Diabetes Metab Res Rev. 36 Suppl 1: e3283. doi:10.1002/dmrr.3283. PMID 32176450 Check |pmid= value (help).
  5. Wukich DK, Armstrong DG, Attinger CE, Boulton AJ, Burns PR, Frykberg RG; et al. (2013). "Inpatient management of diabetic foot disorders: a clinical guide". Diabetes Care. 36 (9): 2862–71. doi:10.2337/dc12-2712. PMC 3747877. PMID 23970716.
  6. Lipsky BA, Berendt AR, Cornia PB, Pile JC, Peters EJ, Armstrong DG; et al. (2012). "2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections". Clin Infect Dis. 54 (12): e132–73. doi:10.1093/cid/cis346. PMID 22619242.
  7. 7.0 7.1 Frykberg, Robert G. (1998). "Diabetic foot ulcers: Current concepts". The Journal of Foot and Ankle Surgery. 37 (5): 440–446. doi:10.1016/S1067-2516(98)80055-0. ISSN 1067-2516.
  8. Apelqvist J, Bakker K, van Houtum WH, Schaper NC, International Working Group on the Diabetic Foot (IWGDF) Editorial Board (2008). "Practical guidelines on the management and prevention of the diabetic foot: based upon the International Consensus on the Diabetic Foot (2007) Prepared by the International Working Group on the Diabetic Foot". Diabetes Metab Res Rev. 24 Suppl 1: S181–7. doi:10.1002/dmrr.848. PMID 18442189.
  9. Holstein PE, Sørensen S (1999). "Limb salvage experience in a multidisciplinary diabetic foot unit". Diabetes Care. 22 Suppl 2: B97–103. PMID 10097908.
  10. Frykberg RG, Armstrong DG, Giurini J, Edwards A, Kravette M, Kravitz S; et al. (2000). "Diabetic foot disorders: a clinical practice guideline. American College of Foot and Ankle Surgeons". J Foot Ankle Surg. 39 (5 Suppl): S1–60. PMID 11280471.
  11. American Diabetes Association (1999). "Consensus Development Conference on Diabetic Foot Wound Care: 7-8 April 1999, Boston, Massachusetts. American Diabetes Association". Diabetes Care. 22 (8): 1354–60. doi:10.2337/diacare.22.8.1354. PMID 10480782.
  12. 12.0 12.1 12.2 Armstrong, DG; Harkless, LB; Nguyen, H; Krasner, D; Hogge, J (2000). "The potential benefits of advanced therapeutic modalities in the treatment of diabetic foot wounds". Journal of the American Podiatric Medical Association. 90 (2): 57–65. doi:10.7547/87507315-90-2-57. ISSN 8750-7315.
  13. Wieman TJ, Smiell JM, Su Y (1998). "Efficacy and safety of a topical gel formulation of recombinant human platelet-derived growth factor-BB (becaplermin) in patients with chronic neuropathic diabetic ulcers. A phase III randomized placebo-controlled double-blind study". Diabetes Care. 21 (5): 822–7. doi:10.2337/diacare.21.5.822. PMID 9589248.
  14. Veves A, Falanga V, Armstrong DG, Sabolinski ML, Apligraf Diabetic Foot Ulcer Study (2001). "Graftskin, a human skin equivalent, is effective in the management of noninfected neuropathic diabetic foot ulcers: a prospective randomized multicenter clinical trial". Diabetes Care. 24 (2): 290–5. doi:10.2337/diacare.24.2.290. PMID 11213881.


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