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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
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. 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
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, 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
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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
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. More recently Bowler et
al
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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
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. Although the use of
antiseptics in wound care has long been debated, a recent wide-ranging review of
published data by Drosou et al
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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
