Cadexomer Iodine Treatment of Diabetic Foot Ulcers

Ulcers of the lower extremity may be caused by a variety of conditions, including neuropathy, ischemia, venous hypertension, and pressure. Diabetic ulcers are the most common foot injuries leading to amputation of the lower extremity. This comes due to the fact, that most diabetic ulcers have delayed healing and are extremely prone to infections.

Patients with diabetes develop wounds secondary to neuropathy with or without biomechanical abnormalities, peripheral vascular disease with ischemia, or both.(5)

Studies have shown that wounds with >105 microorganisms per gram of tissue may have impaired healing (4). Wounds can be healed quicker if the bacterial load is minimized and thus avoiding DFUs complications (5). Also, biofilms may also lead to chronicity of these wounds and for common infectious complications (6,7). So, suitable antimicrobial therapy may be essential for decreasing the bacterial load and treating infection (8).

Iodine has a long history of being used in the treatment of wounds. Iodine denatures proteins and inactivates membrane structures, membrane structures, and enzymes (9).

Cadexomer iodine is a hydrophilic starch polymer bead, containing 0.9% w/w iodine. A pharmacodynamic study has shown that when in contact with wound exudates, cadexomer iodine releases free iodine (an antiseptic), which reduces the bacterial count (10). It also removes pus and debris, absorbs fluid, and facilitates desloughing (11). To promote the healing of chronic skin ulcers it also maintains a moist environment. Cadexomer iodine's ability to reduce bioburden leading to healing progression seems promising but requires larger future studies.

In 2013, Jamie A Schwartz, Columbia University, New York, NY, USA, and associates published a study in the International Wound Journal,(12) to determine the in vivo effects of cadexomer iodine antibacterial dressing on diabetic foot ulcers that were infected or achieved a critical level of colonization. The study was performed with participants two tertiary medical centres in the USA as a hospital-sponsored and institutional review and the trial was performed according to the Helsinki Declaration and its revisions.

Methods

Individuals were considered eligible for the study if they had a DFU with visible signs of localised clinical infection (including delayed healing, pain/tenderness, increased serous exudate, change in colour of the wound bed, friable, absent or abnormal granulation tissue, pus and odour) or critical colonisation

All considered had a DFU grade I or II according to the Meggitt–Wagner scale, had a DFU that was suitable to be dressed with cadexomer iodine, and had at least dopplerable pedal pulses.

Patients were excluded from the study if they had a known sensitivity to iodine or any of the ingredients of the dressing, had a history of thyroid disorders, had renal impairment (Creatinine clearance of <80 ml/min), were currently taking Lithium, had ≥ Grade III DFU on the Meggitt–Wagner scale, had a wound <2 cm in diameter, had an ulcer that was not exuding, had recent treatment with cadexomer iodine or other topical antibacterials in the last 30 days or recent treatment with antimicrobials.

Dropouts were excluded and all those eligible for inclusion into the study were assigned to the same dressing regime with cadexomer iodine. The duration of therapy was 6 weeks, or until wound closure

With this, Fifteen patients corresponding to 16 total DFUs met the criteria of displaying clinical signs of infection or critical colonization and were suitable for a topical antibacterial dressing. One patient had diabetes type I (6·3%) and 15 patients had diabetes type II (93·8%). They underwent weekly treatment for 6 weeks. Cultures were taken at weeks 0, 3 and 6 as appropriate. Ulcer assessment, surrounding skin assessment, photographs, wound tracing and depth, dressing application, possible use of and reason to use a secondary dressing were all recorded at interim visits on weeks 1, 2, 3, 4 and 5. At week 3, an interim study biopsy was taken, and at week 6 a final biopsy was taken. These biopsies were performed immediately adjacent to the previous biopsy sites. All wounds were debrided at each visit prior to the placement of the new dressing. A premature biopsy of the DFU was taken at week 4 or 5 if it was thought to possibly heal prior to final study visit on week 6.

The primary outcome measure was to quantify the reduction of microbial load within these DFU after debridement and treatment with cadexomer iodine over a 6-week period.

Secondary outcomes evaluated included change in ulcer surface area, depth, varying wound bed tissue types, character of surrounding skin and time to resolution of clinical infection/colonisation over the 6-week treatment period.

Results

With the trial, the researchers saw the following results

• At week 3- a median log10 bacterial count reduction of 0.3 was observed from baseline. Over the study period, there was a 53.6% median reduction of the wound surface area. There were no patients that completely healed their ulcer over the 6 week study period. There was a statistically significant median reduction in the bacterial load over the 6 weeks as well as 3 weeks. The median bacterial reduction was 89·2% from baseline to week 6 and 46·2% from baseline to week 3.

• There was a median reduction of 53.6% in ulcer surface area and 50% in ulcer depth from baseline to final.

• The most common initial wound microflora was Methicillin-resistant S. aureus (29・4%) followed by Pseudomonas aeruginosa (11・8%).

• 43.8% patients that originally had a 'clinically' infected ulcer at baseline no longer had a 'clinical' infection at the end of the study, while 12.5% appeared to remain clinically infected at the study completion. Seven patients (43.8%) remained non infected from a clinical standpoint for the entire study period. A McNemars test provided significant evidence of a reduction in the signs of 'clinical' infection from baseline to the final assessment

• The ulcers' appearance notably changed throughout the treatment period with cadexomer iodine. The percentage of beefy red tissue increased from a median of 55% to a median of 85% at the conclusion of the trial. There was a median of 60% healthy tissue (a combination of the % pink epithelial and % beefy red granulation tissue) noted at baseline and this increased to 90% at the final assessment, which represented a marginally statistically significant increase in healthy tissue from baseline to the final assessment.

• Out of 10 patients whose pain levels were recorded, five patients had decreased pain with treatment, four patients experienced no change and one patient had a mild to moderate increase in pain

The study data revealed that Cadexomer iodine was able to achieve a statistically significant reduction in DFU bioburden from baseline to study completion, which supports the use of cadexomer iodine as a treatment to reduce the bacterial counts in diabetic foot ulcers. Also, the reduction in bioburden from ulcer baseline was found to be statistically significant at the 3-week study period, although not as striking as after 6 weeks of treatment.

According to the study authors, this is the first study that has evaluated the actual in vivo effect of cadexomer iodine on the bioburden of a DFU. The authors presumed that if the bioburden is minimal the Diabetic foot ulcers will have more favourable healing progression, and the other DFU variables examined should improve relative to the decreased level of bioburden.

Not many studies of antimicrobial dressings have not assessed the bacterial effect in vivo. This study provided the first evaluation of the effect of cadexomer iodine on the bioburden reduction of DFUs. After collecting and analyzing the data, the researchers proposed an algorithm designed to decrease the bioburden and ultimately heal difficult to treat DFU. Initial treatment is pressure off-loading and mechanical (sharp) debridement for necrotic debris removal and decreasing the bioburden (and potential biofilm) of the wound. After sharp debridement follows the application of daily or every other day topical antibacterial to the Diabetic Foot Ulcers. The ideal properties of the topical preparation are proven antibacterial efficacy (ideally against biofilms as well), wound fluid absorption, maintenance debridement, and balancing of the wound environment

The above article has been published by Medical Dialogues under the MD Brand Connect Initiative. For more details on Cadexomer Iodine, click here

References:

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10. Gottardi W. Iodine and Iodine Compounds. In: Block SS, ed. Disinfection, Sterilization and Preservation. 4th ed. Philadelphia, PA; 1991: 152–166.

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12. Schwartz, J.A., Lantis, J.C., II, Gendics, C., Fuller, A.M., Payne, W. and Ochs, D. (2013), A prospective, non comparative, multicenter study to investigate the effect of cadexomer iodine on bioburden load and other wound characteristics in diabetic foot ulcers. International Wound Journal, 10: 193-199. doi:10.1111/j.1742-481X.2012.01109.x