A Guide To Emerging Advances In Diabetic Foot Ulcer Healing

By Lee C. Rogers, DPM

In one open-labeled Phase I study currently enrolling patients at Heinrich-Heine University in Dusseldorf, Germany, investigators plan to inject bone marrow-derived stem cells intramuscularly and intra-arterially in those with CLI. They will measure ABI, walking distance, capillary oxygen saturation and venous plethysmography as outcomes.

RT-PCR: Is It Faster Than Waiting For Culture Results?
Of the events that can lead to a diabetic foot amputation, infection is probably the most rapid and life threatening factor. Therefore, it is imperative to recognize infection and begin effective treatment quickly. The diagnosis of foot infection in those with diabetes is a clinical one. Signs and symptoms include erythema, edema, purulence and odor. These signs and symptoms are sometimes accompanied by constitutional signs like fever, leukocytosis and a loss of glucose control. A culture is not necessary to diagnose a diabetic foot infection but clinicians should obtain it when an infection is clinically evident so they can narrow the antibiotic spectrum. Culture and sensitivity results generally take three to five days.

One can obtain a more rapid result with real-time polymerase chain reaction (RT-PCR). Clinicians can perform RT-PCR rapidly within an hour to a few hours. This modality enables physicians to identify pathogenic bacteria and characterize resistance. This in turn allows one to choose the appropriate antibiotic at the time of service or hospitalization. One report, highlighting the use of RT-PCR in a culture negative osteomyelitis, found that the method was able to differentiate S. aureus from S. epidermidis.9

Does Bacteriophage Therapy Have A Role In Managing Diabetic Foot Infections?
While there is no work currently being performed on diabetic foot infections and bacteriophage therapy, it deserves some consideration. Bacteriophages are viruses that infect bacteria and either destroy them or weaken them, allowing host defenses to destroy them.10 In essence, one is giving a bacterium a cold.

Phage therapy itself is not a new concept but the potential application to skin and skin structure infections is new. Phage therapy could emerge as an important advance against multi-drug resistant organisms, such as methicillin-resistant Staphylococcus aureus (MRSA). In a bovine model, anti-Staphylococcus bacteriophage K facilitated an impressive reduction in MRSA strains and resulted in strong anti-staphylococcal activity.11

Granulocyte-colony stimulating factor (G-CSF) induces the release of neutrophils from the bone marrow and improves their function.12 As an adjunctive therapy to antibiotics, G-CSF can enhance the immune response. A meta-analysis of five randomized trials including 167 patients showed that adjunctive G-CSF therapy did not speed the clinical resolution of diabetic foot infections but it was associated with a reduced rate of amputation and subsequent surgical procedures.13 What is most impressive was the number needed to treat (NNT) ratio to gain these benefits was low, suggesting that using G-CSF in certain cases to prevent amputation in severe infections is beneficial and efficacious.

Rethinking Offloading For The Diabetic Foot
Pressure reduction is a key and often underemphasized component of diabetic foot ulcer treatment. Clearly, in most diabetic foot ulcers, it is the pressure of repetitive stress combined with sensory neuropathy that precipitates the foot ulcer. Researchers have tested various modalities for offloading the plantar foot and the total contact cast (TCC) still remains the gold standard.14

In a pilot study, researchers showed that the instant total contact cast (iTCC), which consists of a removable cast walker (RCW) rendered irremovable by wrapping it with cohesive bandage or fiberglass, was more effective than the RCW alone.15 In podiatry’s first National Institutes of Health R01 grant, Lavery and Armstrong will compare the TCC to the iTCC in the treatment of plantar diabetic foot wounds.

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