Effect of cadexomer iodine on the microbial load and diversity of chronic non-healing diabetic foot ulcers complicated by biofilm in vivo

Objectives: The performance of cadexomer iodine was determined against microbial populations from chronicnon-healing diabetic foot ulcers (DFUs) complicated by biofilm in vivo, using molecular, microscopy and zymographymethods.Methods: Chronic non-healing DFUs due to suspected biofilm involvement were eligible for enrolment. DNAsequencing and real-time quantitative PCR was used to determine the microbial load and diversity of tissuepunch biopsies obtained pre- and post-treatment. Scanning electron microscopy and/or fluorescence in situ hybridizationconfirmed the presence or absence of biofilm. Zymography was used to determine levels of woundproteases.Results: Seventeen participants were recruited over a 6month period. Scanning electron microscopy and orfluorescence in situ hybridization confirmed the presence of biofilm in all samples. Eleven participants exhibitedlog10 reductions in microbial load after treatment (range 1-2 log ₁₀) in comparison with six patients whoexperienced <1 log ₁₀ reduction (P"0.04). Samples were tested for levels of wound proteases pre- and posttreatment.Reductions in the microbial load correlated to reductions in wound proteases pre- and posttreatment(P"0.03).Conclusions: To the best of our knowledge, this study represents the first in vivo evidence, employing a range ofmolecular and microscopy techniques, of the ability of cadexomer iodine to reduce the microbial load of chronicnon-healing DFUs complicated by biofilm. Further analyses correlating log reductions to optimal duration of therapyand improvements in clinical parameters of wound healing in a larger cohort are required.