Understanding the efficacy of Cadexomer Iodine in managing Wound Biofilms: Review
Biofilms are aggregates of bacteria growing together in a community surrounded by a protective and adhesive extracellular matrix (ECM) of exopolysaccharides (EPS), extracellular DNA (eDNA), and proteins (1-3). It helps in the long-term survival of the bacteria due to the resistance to hostile conditions, antibiotic treatment, and immune evasion (4,5). Biofilms are known to be more than 1000fold resistant to treatment with conventional antibiotics used normally for treating planktonic cells. Biofilms are often associated with human disease and are responsible for the majority of bacterial infections (7).
Previous studies have shown biofilm to be prevalent in up to 60% of chronic non-healing wounds (8,9). However, in a recent meta-analysis of various studies examining biofilm presence, this number has shown to be closer to 80% (10). Biofilms have been linked to many chronic clinical diseases including middle ear infections, implant-related infections, and chronic lung infections (11). European Society of Clinical Microbiology and Infectious Diseases (ESCMID) has highlighted this clinical impact of biofilms with the conclusion that biofilms cause chronic infections (12). Animal studies have clearly shown a significant impact of bacterial biofilms on wound healing in mice, rabbit, and porcine models (13-15)
Cadexomer iodine (CI) 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 (16). It also removes pus and debris, absorbs fluid, and facilitates desloughing (17). To promote the healing of chronic skin ulcers it also maintains a moist environment. Against biofilm, in recent multiple in vitro models, histology results suggested that the CI physically dehydrates and absorbs bacteria and biofilm microcolonies to the cadexomer bead effectively, and these are rapidly killed by iodine (18), thus indicating the superior efficacy of CI.
Despite the wide use of CI as a topical antimicrobial in wounds complicated by biofilm, there is little evidence on their in vivo performance against biofilms/microbial communities. To bridge this gap and to assess the efficacy of CI in human wounds 2 notable studies were undertaken, both in managing chronic non-healing diabetic foot ulcers (DFUs).
In 2017, Matthew Malone et al, from the High-Risk Foot Service, Liverpool Hospital, Sydney, designed a first-of-its-kind study to determine the performance of cadexomer iodine against microbial populations from chronic non-healing diabetic foot ulcers (DFUs) complicated by biofilm in vivo, using DNA sequencing, real-time quantitative PCR (qPCR), microscopy techniques [scanning electron microscopy (SEM) and fluorescence in situ hybridization (FISH)] and gel zymography. (19) Researchers published the findings in the Journal of Antimicrobial Chemotherapy.
The study population involved seventeen participants recruited over 6 months diagnosed with chronic non-healing DFUs (gt;6 weeks duration failing to respond to standard care) where Cadexomer iodine was applied every second day over a 7 day treatment period. The primary endpoint assessed was a reduction in microbial load 7 days post-treatment.
On analysis, the following key facts emerged.
Scanning electron microscopy and or fluorescence in situ hybridization confirmed the presence of biofilm in all samples.
Eleven participants exhibited log10 reductions in microbial load after treatment (range 1–2 log10) in comparison with six patients who experienced < log10 reduction (P = 0.04). Samples were tested for levels of wound proteases pre- and post-treatment.
Reductions in the microbial load correlated to reductions in wound proteases pre- and post-treatment.
In yet another study, published in the International Wound Journal in 2019, researchers compared the impact of two vs. six weeks of topical CI therapy on wound metrics and optimal duration of treatment in 18 participants with chronic non-healing diabetic foot ulcers and suspected biofilm involvement. Tissue biopsies from the ulcers were taken and put to DNA sequencing, polymerase chain reaction (PCR), and Scanning electron microscopy.
On data analysis, the following facts came forth.
Cadexomer Iodine resulted in a mean microbial load reduction of 0.5 Log10 (range = 0-2 Log10) regardless of treatment durations of two or six weeks.
Regardless of treatment duration, there was no statistical difference in the reduction of total microbial loads. No difference in the rate of wound healing in the two groups was seen at 6 weeks.
All ulcers in both groups showed an initial reduction in wound size with the application of Cadexomer Iodine, which reflects its effect on biofilms.
No adverse events were reported.
Acknowledging the superior efficacy of CI among topical antimicrobials in the healing of chronic DFUs, both the studies have highlighted the following key facts.
Cadexomer Iodine disrupts microbial community composition through shifts in richness and diversity, usually by reduction of the abundance of potentially pathogenic genera. Disruption to a chronic infective process may allow the host to restore the normal reparative process of wound healing.
Molecular methods also demonstrated that cadexomer iodine had a broad level of antimicrobial activity in reducing both facultative anaerobes such as Staphylococcus spp., Serratia spp., Pseudomonas spp. and obligate anaerobes including Clostridiales family XI.
The duration of treatment with topical Cadexomer Iodine required to disrupt any pathogenic process could be shorter in small ulcers because there is less tissue to repair in contrast to larger ulcers, which have more tissue to repair.
As facultative and obligate anaerobes form the basis of the microflora in chronic non- healing DFU samples, the reduction of the same supports the fact that CI has a deeper penetrability to other topical microbial.
As both the studies were pilot studies, the researchers have recognized that analyses correlating log reductions to the optimal duration of therapy and improvements in clinical parameters of wound healing with Cadexomer Iodine, in a larger cohort, are required further.
References:
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