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      Cadexomer iodine effectively reduces bacterial biofilm in porcine wounds ex vivo and in vivo

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          Abstract

          Biofilms are prevalent in non‐healing chronic wounds and implicated in delayed healing. Tolerance to antimicrobial treatments and the host's immune system leave clinicians with limited interventions against biofilm populations. It is therefore essential that effective treatments be rigorously tested and demonstrate an impact on biofilm across multiple experimental models to guide clinical investigations and protocols. Cadexomer iodine has previously been shown to be effective against biofilm in various in vitro models, against methicillin‐resistant Staphylococcus aureus biofilm in mouse wounds, and clinically in diabetic foot ulcers complicated by biofilm. Similarities between porcine and human skin make the pig a favoured model for cutaneous wound studies. Two antiseptic dressings and a gauze control were assessed against mature biofilm grown on ex vivo pig skin and in a pig wound model. Significant reductions in biofilm were observed following treatment with cadexomer iodine across both biofilm models. In contrast, silver carboxymethylcellulose dressings had minimal impact on biofilm in the models, with similar results to the control in the ex vivo model. Microscopy and histopathology indicate that the depth of organisms in wound tissue may impact treatment effectiveness. Further work on the promising biofilm efficacy of cadexomer iodine is needed to determine optimal treatment durations against biofilm.

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          Most cited references45

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          Biofilms in chronic wounds.

          Chronic wounds including diabetic foot ulcers, pressure ulcers, and venous leg ulcers are a worldwide health problem. It has been speculated that bacteria colonizing chronic wounds exist as highly persistent biofilm communities. This research examined chronic and acute wounds for biofilms and characterized microorganisms inhabiting these wounds. Chronic wound specimens were obtained from 77 subjects and acute wound specimens were obtained from 16 subjects. Culture data were collected using standard clinical techniques. Light and scanning electron microscopy techniques were used to analyze 50 of the chronic wound specimens and the 16 acute wound specimens. Molecular analyses were performed on the remaining 27 chronic wound specimens using denaturing gradient gel electrophoresis and sequence analysis. Of the 50 chronic wound specimens evaluated by microscopy, 30 were characterized as containing biofilm (60%), whereas only one of the 16 acute wound specimens was characterized as containing biofilm (6%). This was a statistically significant difference (p<0.001). Molecular analyses of chronic wound specimens revealed diverse polymicrobial communities and the presence of bacteria, including strictly anaerobic bacteria, not revealed by culture. Bacterial biofilm prevalence in specimens from chronic wounds relative to acute wounds observed in this study provides evidence that biofilms may be abundant in chronic wounds.
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            Why chronic wounds will not heal: a novel hypothesis.

            The present paper presents a hypothesis aimed at explaining why venous leg ulcers, pressure ulcers, and diabetic foot ulcers develop into a chronic state. We propose that the lack of proper wound healing is at least in part caused by inefficient eradication of infecting, opportunistic pathogens, a situation reminiscent of chronic Pseudomonas aeruginosa infections found in patients suffering from cystic fibrosis (CF). We have analyzed sections from chronic wounds by fluorescence in situ hybridization and found distinct microcolonies--the basal structures of bacterial biofilms. Several researchers have previously reported that another important hallmark of biofilm formation is development of increased tolerance to various antimicrobial measures and treatments. Furthermore, the immune response to infecting bacteria in the cystic fibrosis lung is dominated by polymorphonuclear neutrophils (PMNs), and we have recently shown that in vitro biofilms of P. aeruginosa produce a shielding mechanism that offers protection from the phagocytic activity of PMNs. We hypothesize that the presence of P. aeruginosa in biofilms, and the lack of concomitant elimination by attended PMNs, are the main causes of inefficient eradication by antibiotic treatment and antimicrobial activity of the innate immune system, respectively.
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              Nonrandom distribution of Pseudomonas aeruginosa and Staphylococcus aureus in chronic wounds.

              The spatial organization of Pseudomonas aeruginosa and Staphylococcus aureus in chronic wounds was investigated in the present study. Wound biopsy specimens were obtained from patients diagnosed as having chronic venous leg ulcers, and bacterial aggregates in these wounds were detected and located by the use of peptide nucleic acid-based fluorescence in situ hybridization and confocal laser scanning microscopy (CLSM). We acquired CLSM images of multiple regions in multiple sections cut from five wounds containing P. aeruginosa and five wounds containing S. aureus and measured the distance of the bacterial aggregates to the wound surface. The distance of the P. aeruginosa aggregates to the wound surface was significantly greater than that of the S. aureus aggregates, suggesting that the distribution of the bacteria in the chronic wounds was nonrandom. The results are discussed in relation to our recent finding that swab culturing techniques may underestimate the presence of P. aeruginosa in chronic wounds and in relation to the hypothesis that P. aeruginosa bacteria located in the deeper regions of chronic wounds may play an important role in keeping the wounds arrested in a stage dominated by inflammatory processes.
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                Author and article information

                Contributors
                schultzg@ufl.edu
                Journal
                Int Wound J
                Int Wound J
                10.1111/(ISSN)1742-481X
                IWJ
                International Wound Journal
                Blackwell Publishing Ltd (Oxford, UK )
                1742-4801
                1742-481X
                13 March 2019
                June 2019
                : 16
                : 3 ( doiID: 10.1111/iwj.2019.16.issue-3 )
                : 674-683
                Affiliations
                [ 1 ] Advanced Wound Management R&D, Smith & Nephew Fort Worth Texas
                [ 2 ] Clinical, Scientific and Medical Affairs, Smith & Nephew Kingston upon Hull UK
                [ 3 ] Department of Obstetrics and Gynecology, Institute for Wound Research University of Florida Gainesville Florida
                Author notes
                [*] [* ] Correspondence

                Gregory S. Schultz, PhD, Department of Obstetrics and Gynecology, Institute for Wound Research, University of Florida, 1600 South West, Archer Road, Room M337F, Gainesville, FL 32610‐0294.

                Email: schultzg@ 123456ufl.edu

                Author information
                https://orcid.org/0000-0002-2054-2240
                Article
                IWJ13080
                10.1111/iwj.13080
                6850490
                30868761
                fdef6fed-b759-4de7-baa9-52d9ddbadffb
                © 2019 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

                History
                : 26 October 2018
                : 04 January 2019
                : 08 January 2019
                Page count
                Figures: 5, Tables: 1, Pages: 10, Words: 7361
                Funding
                Funded by: Smith & Nephew plc
                Categories
                Original Article
                Original Articles
                Custom metadata
                2.0
                June 2019
                Converter:WILEY_ML3GV2_TO_JATSPMC version:5.7.1 mode:remove_FC converted:12.11.2019

                Emergency medicine & Trauma
                biofilms,cadexomer iodine,porcine,silver,wounds
                Emergency medicine & Trauma
                biofilms, cadexomer iodine, porcine, silver, wounds

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