Non-surgical options for DFUs: Medication and Adjunctive Therapy

Pharmacotherapy and Complementary Medicine
(Medication and Adjunctive Therapy)

The non-surgical treatment for diabetic foot ulcers (DFUs) involving various medications and therapies. However, due to varying levels of evidence, this article will only introduce few common treatment methods and some alternative therapies. Professional medical advice should be sought when applying these treatments in practice.

Medication：Antibiotic Therapy

Correct identification of infection and proper use of antibiotics to treat ulcer wounds are critical for improving the prognosis of patients with DFUs. The Infectious Diseases Society of America (IDSA) recommends at least one week of antibiotic therapy for wounds with two or more inflammatory signs (erythema, fever, tenderness, pain, induration) or purulent secretions1. Antibiotics are not recommended as prophylactic drugs for patients without infections2.

What are the symptoms of infection?

"Foot Infection: The Five Early Signs You Need to Know"

Adjunctive Therapies

1. Non-surgical debridement1,3

   Autolytic： such as hydrogel

   Enzymatic：such as collagenase from Clostridium

   Mechanical：such as hydro-surgery

   Biological：such as maggot debridement therapy

   There are many options for non-surgical debridement, but they should be used under the evaluation and advice of a physician. Surgical debridement remains the primary debridement method recommended by the International Working Group on the Diabetic Foot guidelines (IWGDF guidelines)4,5.

2. Topical Medications

   Include growth factor ointments, immunomodulators, plant extract creams, and other topical medications1,3.

   The American Diabetes Association (ADA) recommends the use of clinically proven dressings and medications to treat DFU wounds6.

   "The Crucial Role of Medication in Wound Care"

   
3. Negative Pressure Wound Therapy (NPWT)1,6

   By using a sealed vacuum device to collect and remove wound exudate, NPWT not only improves tissue perfusion and promotes granulation tissue formation but also cleanses the wound, reducing the frequency of dressing changes.

   IWGDF recommends considering the use of Negative Pressure Wound Therapy to assist with post-operative wound healing4,5.

4. Oxygen Therapy1

   Includes both topical oxygen therapy and systemic hyperbaric oxygen therapy. Oxygen therapy aids in cell proliferation, collagen synthesis, re-epithelialization, and bacterial resistance for the patient’s wound.

   Although some literature has indicated the benefits of oxygen therapy for DFU patients3, due to the need for specific equipment and resources, IWGDF only recommends it as an adjunctive treatment when standard care is ineffective and where resources are available5.

5. Bioengineered Skin Substitutes3

   May involve autologous or allogeneic transplants of tissues (such as the amniotic membrane, fibroblasts, keratinocytes) and cellular matrices. These matrices can act as scaffolds, providing a better environment that facilitates the migration and revascularization of active cells such as fibroblasts.

   Currently, IWGDF does not recommend these types of skin substitutes as routine wound care dressings4,5, with only a few being used as adjunctive therapy when standard care is ineffective.

   Which dressings are recommended by IWGDF?

   "Essentials of DFU Wound Care: Analysis of IWGDF Clinical Guidelines"

   
6. Other Therapies

   Include instrumental treatments (such as electrotherapy, laser, phototherapy, etc.), other oral medications, as well as the more emerging stem cell therapy or gene therapy, etc1,3,5.

Reference：
• Everett E et al. Ann N Y Acad Sci. 2018;1411(1):153-165.
• Senneville É et al. Diabetes Metab Res Rev. 2023;e3687.
• Dixon D et al. Drugs. 2021;81(1):29-56.
• Schaper NC et al. Diabetes Metab Res Rev. 2023;e3657.
• Chen P et al. Diabetes Metab Res Rev. 2023;e3644.
• Lim JZM et al. Journal of the Royal Society of Medicine. 2017;110(3):104-109.