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    An in vitro study of the antimicrobial activity and efficacy of iodine-generating

    hydrogel wound dressings

    R.M.S. THORN BSc*, J. GREENMAN BSc PhD** AND A. AUSTIN BSc +

    * Research Assistant, Department of Microbiology, University of the West of England,

    UK

    **Professor of Microbiology, Department of Microbiology, University of the West of

    England, UK

    + Development Scientist, Insense Ltd., Bedford, UK

    To whom all correspondence should be addressed:

    Professor John Greenman

    Faculty of Applied Sciences, University of the West of England, Frenchay Campus,

    Coldharbour Lane, Bristol, BS16 1QY, United Kingdom

    Telephone: 0117 344 2515

    Fax: 0117 344 2904

    E-mail: [email protected]

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    Abstract

    Objectives: To determine the antimicrobial activity and efficacy of different

    formulations of novel bioxygenating hydrogels against various target organisms by

    means of an in-vitro test system that more effectively mimics the conditions

    encountered when dressings are in contact with wounds.

    Methods: Cellulose filter discs (n = 32) were inoculated with indicator species and

    placed equidistant from each other as a matrix onto agar test beds. Cut squares of

    control or test dressings were placed on top of each disc. Kill curves were constructed

    from determinations of the numbers of survivors (log cfu disc -1

    ) over time by

    removing disc samples at various time points.

    Results: Significant differences (piodozyme 401>oxyzyme) was the same regardless of the target species.

    Conclusions: The novel hydrogel skin surface wound dressings are broad spectrum in

    activity, encompassing antibiotic resistant organisms, anaerobes and yeasts, and the

    antimicrobial function appears to be rapidly effective.

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    Introduction

    Numerous commercial antimicrobial wound dressings are already available, most of

    which are based on silver as the active ingredient, and new versions are constantly

    being introduced onto the market. Practitioners and other decision-makers are,

    therefore, faced with a need to make rational choices between different supposedly

    antimicrobial dressings, but there is little objective evidence on which to base these

    choices. There is a real need to understand more about the complex underlying nature

    of wound infections, as well as the interaction between the wound, the microbial flora

    and the dressing. Simple laboratory evaluations of antimicrobial potency can be very

    misleading, especially with modern composite dressings, because the tests fail to take

    account of this complex interaction. For these reasons, there is a particular need for

    in-vitro laboratory tests that take into account at least the most basic aspects this

    interplay of factors, especially the way in which wound microbes are bathed in fluid

    rich on organic, nutritional substances, most of which are drawn into the dressing

    where they can inactivate antimicrobial agents.

    Wound management must always take into account the risk of clinical infection

    becoming established. Microbial colonisation occurs in virtually all acute, traumatic,

    surgical and chronic wounds. Often, colonisation involves potentially pathogenic

    organisms that can lead to a wound becoming infected with organisms that cause

    serious complications. It is widely recognised that such infections delay healing,

    thereby causing increased trauma to the patient and increasing treatment costs, which

    isa the reason for a growing demand for effective wound management and therapeutic

    options to limit the risk of infection 1 . Burns, diabetic foot ulcers, leg ulcers and

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    decubitus ulcers are particularly prone to complications resulting from infection. For

    example it is estimated 75% of deaths following burn injuries are related to infection 2 .

    Although systemic antibiotics are regarded as the ultimate treatment against

    wound infection, antiseptic skin surface dressings have long been used to control

    wound micro flora and, in normal clinical practice, to combat infection. Antibiotics

    have been shown to be inappropriate in some cases 3 , and can result in wound

    colonization by resistant organisms 4 . When treating wounds colonised with bacteria

    resistant to conventional antibiotics (e.g. MRSA), it is important to contain the

    bacteria within the colonised wound to prevent cross-infection (particularly in a

    hospital environment), thus making wound management through skin dressings

    essential.

    There is wide variation in the efficacy of currently available skin surface

    dressings at combating wound infection. It has been shown that the rate of clinical

    infection is lower under occlusive dressings than non-occlusive dressings 5 and that, in

    contrast to dry dressings (e.g. absorbent cellulose), dressings that promote moist

    wound healing (e.g. hydrocolloids) offer external protection to the wound and limit

    the spread of bacteria by aerosol formation upon removal 6 . More recently Bowler et

    al 7 demonstrated the effective sequestering and retention of micro-organisms by a

    hydrofiber dressing in vitro, which could help to reduce the microbial load in wounds

    and the surrounding environment.

    Antimicrobial agents can be incorporated into skin surface wound dressings,

    although this tends to be limited to antiseptics, as the routine use of topical antibiotics

    to treat colonized or infected wounds is seen as unjustified 8 . Although the use of

    antiseptics in wound care has long been debated, a recent wide-ranging review of

    published data by Drosou et al 9 concluded that “antiseptics need not be omitted from

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    the therapeutic armamentarium of wound care”, quoting limited toxicity data, broader

    antimicrobial spectrum and lower sensitization rates. Because antiseptics incorporated

    into skin surface wound dressings are in contact with the wound for much longer than

    in solution form, they can be more dilute, less toxic, and exert a prolonged

    antimicrobial effect 8 .

    As wound dressing technology becomes more advanced, new developments

    are emerging in which antimicrobial agents are delivered in a controlled manner from

    composite dressings that also interact with the wound. For example, the new

    OXYZYME (oxyzyme) and IODOZYME (iodozyme) wound dressings utilise an

    enzyme (glucose oxidase) to drive the transport of oxygen into the wound and the

    synthesis in-place of a predetermined dose profile of iodine (fig 1.). The integration

    of antiseptic iodine with oxygenation of the wound bed provides an effect described

    as wound “bioxygenation”. Currently, these biochemically active wound dressings

    are built into a hydrogel matrix, consisting of three dimensional networks of

    hydrophilic polymers that are flexible, non-antigenic, and capable of absorbing large

    amounts of wound fluid, as well as providing a barrier to external infection 10

    . A moist

    wound healing environment is created by the occlusive nature of the hydrogel sheets,

    as well as their ability to donate moisture. This moist environment has been shown to

    be associated with decreased healing time, greater patient comfort and reduced

    costs 11

    .

    The steady release of iodine exerts a gentle, surface antimicrobial effect at the

    interface between wound and dressing, ideal in treatment of wounds where the fear of

    infection is an issue. This antimicrobial effect can be further enhanced by adjusting

    the reaction conditions within the gel layers to create the iodozyme system, in which

    higher levels of iodine are synthesised. In principle, the system allows for any

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    practicable level of iodine to be generated, simply by appropriately modifying

    concentrations of enzyme and iodide, as well as pH, surfactant concentration and the

    dimensions of the gel layers.

    The antimicrobial activity of such composite, multifunctional dressings is not

    easily evaluated by any of the previously established in-vitro methods, since it is

    essential for any such evaluation to take account of the system’s controlled

    mechanism of action and its potential to interact with the wound. The key features of

    oxyzyme and iodozyme hydrogel systems to be taken into account are the mechanism

    and dynamics of iodine generation, the associated oxygen production and the steady

    take-up of wound-fluid (which causes an associated swelling and dilution of the

    biochemical constituents). Under aerobic, in-vitro conditions, it is difficult to

    measure the full impact of the oxygenation effect (which depends on the involvement

    of leukocytes), even though the oxygen delivery mechanism will be active. However,

    the new test system used in this study enables the antimicrobial efficacy of the gradual

    synthesis and release of iodine from the dressings to be determined. Moreover the test

    system also allows evaluation against anaerobes.

    The specific aim of this in vitro study was to dete

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