Keith Cutting

Microbiology of the skin and the role of biofilms in infection

The integrity of human skin is central to the prevention of infection. Acute and chronic wounds can develop when the integrity of skin as a barrier to infection is disrupted. As a multi‐functional organ, skin possesses important biochemical and physical properties that influence its microbiology. These properties include a slightly acidic pH, a low moisture content, a high lipid content (which results in increased hydrophobicity) and the presence of antimicrobial peptides. Such factors have a role to play in preventing exogenous microbial colonisation and subsequent infection. In addition, the properties of skin both select for and enhance colonisation and biofilm formation by certain ‘beneficial’ micro‐organisms. These beneficial micro‐organisms can provide further protection against colonisation by potential pathogens, a process known as colonisation resistance. The aim of this paper is to summarise the microflora of skin and wounds, highlighting the role of certain micro‐organisms and biofilms in associated infections.

The safety and efficacy of dressings with silver – addressing clinical concerns

Dear Sirs The authors (1) are to be commended for drawing the attention of the readers the very important topic of reducing wound bioburden with topical silver compounds and silverimpregnated dressings. As rightly stated, silver is ideally suited as a topical antibacterial and antifungal agent. In fact, silver compounds have been exploited for their medicinal properties for centuries, and at present, silver has re-emerged as a viable treatment option for infections encountered in burns, open wounds and chronic ulcers. The challenges were and still are, however, how to deliver the optimal concentration of ionic silver Ag+ (the active form) and how to maintain this concentration for the longest period of time after application (2). As the industry continues to struggle to resolve these issues, clinicians seem to remain concentrated at the valuable antibacterial and antifungal effect of the silver products and dressings or by the way of any other topical agent, without much concern about their possible toxicity and in particular their negative effect on wound healing. Silver products, by controlling wound bioburden, would definitely secondarily promote wound healing; however, it must be stressed that their recently demonstrated primary cytotoxic effect on fibroblasts and keratinocytes is a clear indication of their negative impact on wound healing (2). Irrespective of the source of silver, whether released from solutions, creams and ointments or nanocrystalline silver released from commercially available new dressings, silver is highly toxic to both keratinocytes and fibroblasts (2). Moreover, in addition to this definite cytotoxicity, we have recently demonstrated in an experimental study (3) that topical application of silver sulphadiazine modulates various wound healing cytokines in a way affecting negatively the mechanisms of wound healing. As stressed by the authors, there are still numerous questions to be answered in respect of silver in wound care. Silver dressings, as antimicrobial therapies, must be dictated by clear criteria of wound sepsis and are not indicated for long-term use. Regular wound assessment should guide the further use of the dressings and duration of treatment should be according to clinical needs and guided by treatment targets (1). Although the effects of the available various silver products on wound infection and wound healing are variable, ultimately, no matter how sophisticated the delivery system, the agent silver cannot be expected to make a selective kill (2). The dilemma in product development is to produce an agent and system of delivery, which maximises the lethal effect for bacteria and minimises the damage to human cells, and the ultimate goal remains the choice of a product with a superior profile of antimicrobial activity over cellular toxicity (2).

Microbiology of wounds.

Chronic wounds are a serious public health issue. The incidence and prevalence of the different types of chronic wounds are largely unknown worldwide, but 13 years ago George1 estimated the worldwide burden of wounds to be: Surgical wounds, 40 to 50 millio• n • Leg ulcers, 8 to 10 million • Pressure ulcers, 7 to 8 million • Burns, 7 to 10 million In the United States alone, the estimated number of chronic wounds includes 1 to 2 million diabetic foot ulcers, 1 to 2 million venous leg ulcers, 3 to 5 million pressure ulcers, and 1% surgical site infections. One of the underlying pathologies known to increase the prevalence of chronic wounds is diabetes mellitus. Diabetes mellitus in the Western world is growing continuously at a double-digit rate. However, this figure is not truly representative of the extent of the problem. Figures from the Centers for Disease Control and Prevention (CDC) state that there are approximately 24 million patients with diabetes mellitus (24 million diabetics). Cutaneous wounds in the United States alone cost society over

Topical silver-impregnated dressings and the importance of the dressing technology

25 billion annually. The management of infected wounds remains an area of confusion and hence great debate. No definition or authoritative clinical guidelines of what constitutes an infected wound exists. Terminology in wound care such as colonization, critical colonization, biofilm, and other descriptions of bacterial behavior on the surface of the wound are not clearly defined. Even the term infection requires redefining in light of recently generated insight into the prevalence and behavior of the biofilm phenotype. In addition, many of the concepts concerning wound infections are not backed up with meaningful scientific support. Consequently many terms used in wound care have led to confusion and unnecessary or inappropriate management of chronic wounds. It is well established that wound healing is dynamic, infinitely complex, nonlinear, and prodigiously individualized to the context of the patient. Understanding the intricacies of chronic wounds becomes even more complex when one considers the myriad of host variables that contribute to the disease state. The plausible common barrier that may impair many of these wounds from healing is chronic infection as a result of biofilm infection. Chronic biofilm-based infections constitute 80% of all human infection. Accordingly, acute infections remain as the minority census of all infectious disease. The definition of acute infection is based on clinical characteristics of rapid onset and aggressive bacterial behavior, which responds rapidly and completely to antibiotics or the host immune response. Chronic infections are persistent and recalcitrant. It is interesting to note that acute and chronic infections have not been clearly differentiated on a molecular level and may be explained by bacteria pursuing widely divergent survival strategies only now becoming elucidated through research.

Fundamentals of randomized clinical trials in wound care: Design and conduct

A wide variety of silver‐impregnated wound dressings has become available in recent years. This has given the practitioner choice but little evidence by which an appropriate dressing may be selected. In many instances, the ancillary function(s) of the dressing will become differentiating factors that influence choice. For example, the dressing capacity to manage exudate, maintain an optimum moist environment, reduce or avoid maceration, maintain an intimate contact with the wound bed, promote autolytic debridement, sequester bacteria and bind matrix metallo proteases (MMPs) are some of those functions that are of clinical significance and may dictate choice. In this article we present the evidence for these functions, thereby enabling practitioners to evaluate comparative dressing attributes, and so make an informed choice of which silver dressing best suits the needs of the wound under differing circumstances.

Wound infection, dressings and pain, is there a relationship in the chronic wound?

The care for chronic and acute wounds is a substantial problem around the world. This has led to a plethora of products to accelerate healing. Unfortunately, the quality of studies evaluating the efficacy of such wound care products is frequently low. Randomized clinical trials are universally acknowledged as the study design of choice for comparing treatment effects, as they eliminate several sources of bias. We propose a framework for the design and conduct of future randomized clinical trials that will offer strong scientific evidence for the effectiveness of wound care interventions. While randomization is a necessary feature of a robust comparative study, it is not sufficient to ensure a study at low risk of bias. Randomized clinical trials should also ensure adequate allocation concealment and blinding of outcome assessors, apply intention‐to‐treat analysis, and use patient‐oriented outcomes. This article proposes strategies for improving the evidence base for wound care decision making.

Fundamentals of randomized clinical trials in wound care: Reporting standards

The focus on quality of life issues in wound care has justly taken a far greater importance. With the acceptance that pain can be a major factor to the patient, and in particular, pain at dressing change comes the opportunity for avoidance and/or reduction strategies. Whilst pain has been associated with wound infection for millennia, it is only much more recently that this has received due attention from research and clinical practice. In this study, the nature of pain, changes in pain and pain associated with infection are the focal points. A Delphi approach, now a frequently used tool in wound care research, has been used to obtain expert opinion on these aspects of management.

Biofilms: possible strategies for suppression in chronic wounds.

In wound care research, available high‐level evidence according to the evidence pyramid is rare, and is threatened by a poor study design and reporting. Without comprehensive and transparent reporting, readers will not be able to assess the strengths and limitations of the research performed. Randomized clinical trials (RCTs) are universally acknowledged as the study design of choice for comparing treatment effects. To give high‐level evidence the appreciation it deserves in wound care, we propose a step‐by‐step reporting standard for comprehensive and transparent reporting of RCTs in wound care. Critical reporting issues (e.g., wound care terminology, blinding, predefined outcome measures, and a priori sample size calculation) and wound‐specific barriers (e.g., large diversity of etiologies and comorbidities of patients with wounds) that may prevent uniform implementation of reporting standards in wound care research are addressed in this article. The proposed reporting standards can be used as guidance for authors who write their RCT, as well as for peer reviewers of journals. Endorsement and application of these reporting standards may help achieve a higher standard of evidence and allow meta‐analysis of reported wound care data. The ultimate goal is to help wound care professionals make better decisions for their patients in clinical practice.