Abstract

The care of patients with a wound infection may appear inconsistent: a number of different antibiotic preparations may be used over time in an effort to control the causative organism; and a variety of different management strategies may be employed by different healthcare practitioners. With the advent of Independent (Supplementary) Nurse Prescribing courses and the future potential for nurses with suitable qualifications to prescribe antibiotics for patients with wound infections [1], there is clearly a need for nurses and other practitioners to review and update their knowledge of this important subject.

Introduction
The development of a wound infection depends on the complex interplay of many factors. If the integrity and protective function of the skin is breached, large quantities of different cell types will enter the wound and initiate an inflammatory response. This may be characterised by the classic signs of redness, pain, swelling, raised temperature and fever [2]. This process ultimately aims to restore homeostasis. The potential for infection depends on a number of patient variables such as the state of hydration, nutrition and existing medical conditions as well as extrinsic factors, for example related to pre-, intra-, and post-operative care if the patient has undergone surgery. This often makes it difficult to predict which wounds will become infected [3]. Consequently the prevention of wound infection should be a primary management objective for all healthcare practitioners. The 2002 survey report by the Nosocomial Infection National Surveillance Service (NINSS), which covers the period between October 1997 and September 2001, indicates that the incidence of hospital acquired infection (HAI) related to surgical wounds is as high as 10%. These infections complicate illness, cause anxiety, increase patient discomfort and can lead to death. The cost to the NHS is almost 1 billion pounds per annum [4]. Infections of the surgical wound are one of the most common HAIs and are an important cause of morbidity and mortality. The delay in recovery and subsequent increased length of hospital stay also has economic consequences. It has been estimated that each patient with a surgical site infection will require an additional 6.5 days in hospital, which results in the doubling of hospital costs associated with that patient [5].

Historical background
Wound infection is not a modern phenomenon. As early as 14-37AD there is documentary evidence that Cornelius Celsus (a Roman physician) described the four principal signs of inflammation and used 'antiseptic' solutions. Another Roman physician, Claudius Galen (130-200 AD) had such an influence on the management of wounds that he is still thought of by many today as the 'father of surgery'. It should also be remembered that he and some of his followers instigated the 'laudable pus' theory, which incorrectly considered the development of pus in a wound as a positive part of the healing process[6]. Further historical references are listed in Table 1 [7].
Table 1: Historical background (1510-1994)

Ambrose Pare (1510-1590) Semmelweiss (1818-1865), Pasteur (1822-1895) and Lister (1827-1912) Florence Nightingale (1894)

Encouraged wounds to suppurate Accepted germ theory and introduced antiseptics

'Not in bacteriology but looking into drains (for smells) is the thing needed'. Held a firm belief in the benefit of hand-washing and strict hygiene Defined terminology in current use for wound infection Identified the concept of 'critical colonisation' with fresh insights into chronic wound healing and non-healing wounds

Mary Ayton (1985) Vincent Falanga (1994)

Terminology
It is important to have a clear understanding of the terms used for wound infection. Since 1985 the most commonly used terms have included wound contamination, wound colonisation, wound infection and, more recently, critical colonisation. These terms can be defined as: Wound contamination - the presence of bacteria within a wound without any host reaction [8] Wound colonisation - the presence of bacteria within the wound which do multiply or initiate a host reaction [8] Critical colonisation - multiplication of bacteria causing a delay in wound healing, usually associated with an exacerbation of pain not previously reported but still with no overt host reaction [9], [10] Wound infection - the deposition and multiplication of bacteria in tissue with an associated host reaction [8]

In practice it seems that some experienced tissue viability nurses and medical practitioners use the term 'critical colonisation' to describe wounds that are considered to be moving from colonisation to local infection. The challenge within the clinical setting, however, is to ensure that the majority of practitioners recognise this situation with confidence and for the bacterial bioburden to be reduced as soon as possible, perhaps through the use of topical antimicrobials.

Potential wound pathogens

The majority of micro-organisms are less than 0.1mm in diameter and can therefore only be seen under a microscope. They can be categorised into different groups, such as bacteria, fungi, protozoa and viruses, depending on their structure and metabolic capabilities [11]. Bacteria These are relatively simple cells that can be further categorised according to differences in their shape and cell wall. Cocci (spherical shaped cells), bacilli (rods) and sprirochaetes (spirals) can be arranged singly; however cocci and bacilli can also be found in pairs, chains and irregular clusters. They can be visualised using a bacteriological staining process called Gram staining; after Gram staining, Gram-positive bacteria are purple and Gram-negative bacteria are red. Species that fail to stain with the Gram reaction, such as Clostridia, require specialised stains. The growth and survival of all bacteria is dependent upon environmental factors, for example strict aerobes

require oxygen whereas anaerobes are rapidly killed by oxygen. It is important to note, however, that both aerobes and anaerobes can survive in close proximity to each other and that some can survive in both conditions by growing aerobically and then switching to anaerobic metabolism in the absence of oxygen; these are known as facultative anaerobes. Fungi These are composed of larger more complex cells than bacteria. They are either singlecelled yeasts or multi-cellular organisms with a nuclei contained within a cell membrane. Fungi can be responsible for superficial infections of the skin, nails and hair and, although they have been isolated from wounds, they are rarely pathogenic in this setting [12]. Protozoa These are single celled organisms within a fragile membrane and without a cell wall. They are most significantly associated with infected skin ulcers. Viruses These are composed of genetic material (nucleic acid) enclosed within a protein coat or a membranous envelope. Although viruses do not generally cause wound infections, bacteria can infect skin lesions formed during the course of certain viral diseases. It is important to remember that different micro-organisms can exist in polymicrobial communities and this is often the case within the margins of a wound [13].
Table 2: Examples of potential wound pathogens Gram-positive cocci

Beta Haemolytic Streptococci (Streptococcus pyogenes)* Enterococci (Enterococcus faecalis) Staphylococci (Staphylococcus aureus/MRSA)*

Gram-negative aerobic rods

Pseudomonas aeruginosa*

Gram-negative facultative rods

Enterobacter species Escherichia coli Klebsiella species Proteus species

Anaerobes

Bacteroides Clostridium

Fungi

Yeasts (Candida)

Aspergillus

* Most common causative organisms associated with wound infections MRSA Methicillin-resistant Staphylococcus aureus (MRSA) was first reported in the UK in the 1980s and remains a cause of concern for all healthcare practitioners. There are now many different strains of MRSA affecting a large number of individuals in many different healthcare settings. The degree to which people are affected ranges in severity from simple wound colonisation, which does not need to be treated aggressively, to systemic infection such as bronchopneumonia, which may prove to be fatal. Anecdotal evidence suggests that MRSA is no more pathogenic in a wound than the non-resistant version; however, it is accepted that if a wound is infected with MRSA it is difficult to manage with antibiotics. As a general rule, practitioners should follow the local protocol for the management of a wound colonised with MRSA, with ongoing treatment based on clinical signs.

Wound contamination and the development of infection

There are a number of ways in which micro-organisms can gain access to a wound: Direct contact: eg transfer from equipment or the hands of carers Airborne dispersal: micro-organisms deposited from the surrounding air Self-contamination: physical migration from the patient's skin or gastrointestinal tract

Whilst there is no definitive evidence to identify the most common route of entry for a micro-organism into a wound, direct contact and poor hand-washing techniques of healthcare practitioners during pre- and post-operative phases of patient care are considered to be significant factors. The presence of a micro-organism within the margins of a wound does not indicate that wound infection is inevitable [14]. Protective colonisation may play a part whereby some bacteria produce highly specific proteins that kill or inhibit other, usually closely related, bacterial species or where certain bacteria produce a variety of metabolites and end products that inhibit the multiplication of other micro-organisms [10]. Ultimately the development of an infection will be influenced largely by the virulence of the organism and immunological status of the patient; for example, patients considered most at risk are those being treated with long-term steroids and those receiving chemotherapy. Virulence describes both the pathogenicity (Table 3) and invasiveness of the relevant micro-organism. A number of specific factors have also been identified in relation to infection rates in surgical wounds [15]. These include: Presence of an existing chronic infection Time interval between skin preparation and surgery Nature of the invasive procedure - especially if involving the bowel Extent of tissue loss and/or trauma to tissues during surgery Adequacy of wound drainage Appropriate use of wound management materials.

Specific wound-related factors that may predispose to the development of an infection include: Poor application of the principles of asepsis at the time of wound dressing changes Presence of devitalised tissue within the wound margin - necrotic tissue or slough, particularly if over 50% Nature and prolonged presence of exudate not managed by a closed wound drainage system.

Table 3: Pathogenic effects of virulent micro-organisms Toxin production Superantigen release within the blood stream that initiates an uncontrolled proliferation of T cells Superantigen production Vigorous stimulation of immune cells Stimulation of T (thymus maturing) cell subsets allowing the release of cytokines that initiate cell and tissue damage

Some species of micro-organisms such as the exotoxins of Staphylococcus and Streptococcus produce superantigens A microbial colony encased in an adhesive polysaccharide matrix that is usually attached to a wound surface [11]. Biofilms present in the form of a transparent sticky film covering the wound surface. Cells in biofilms exhibit a decreased sensitivity to host immunological defence mechanisms, decreased susceptibility to antimicrobial agents and increased virulence. They have also been implicated in persistent infections [16]

Presence of biofilms

Recognition of wound infection

The inflammatory response is a protective mechanism that aims to neutralise and destroy any toxic agents at the site of an injury and restore tissue homeostasis [17]. There are a number of indicators of infection, these include the classic signs related to the inflammatory process and further more subtle changes as highlighted by Cutting and Harding [18]. The classic signs of infection include: Localised erythema Localised pain Localised heat Cellulitus Oedema.

Further criteria include: Abscess Discharge which may be viscous in nature, discoloured and purulent Delayed healing not previously anticipated Discolouration of tissues both within and at the wound margins Friable, bleeding granulation tissue despite gentle handling of and the non adhesive nature of wound management materials used Unexpected pain and/or tenderness either at the time of dressing change or reported by the patient as associated specifically with the wound even when the wound dressing is in place Abnormal smell Wound breakdown associated with wound pocketing/bridging at base of wound, ie when a wound that was assessed as healing starts to develop strips of

granulation tissue in the base as opposed to a uniform spread of granulation tissue across the whole of the wound bed. The above criteria should be used as discriminating factors when the 'classic' signs of wound infection do not appear to be present but the presence of a wound infection is suspected, usually as a result of a delay in wound healing that was not anticipated from the patient's medical history or knowledge of the patient's wound.

Confirming a diagnosis of wound infection

If, after careful assessment, it is apparent that the wound is infected, it is important to confirm this and identify the causative organism(s) and possible sensitivities to antibiotics. Wound swabbing is the most common sampling method used throughout the UK although its clinical value has been questioned by a number of authors [13], [19], [20]. It has been suggested that routine swabbing, such as at weekly intervals or at the time of frequent dressing changes, is neither helpful nor cost effective [21]. In purely financial terms, a negative wound swab costs between 15 to 25 per swab - dependent upon the health setting in which it has been obtained - and each requested antibiotic sensitivity will cost an additional 5 per set per organism. Further investigations include: Serum investigations. These involve small amounts of blood being obtained from the patient to identify elevated white cell counts and elevated levels of serum C-reactive protein (CRP), a protein normally not found in the serum, but present in many acute inflammatory conditions and with necrosis. However, it should be remembered that the latter is not diagnostic of a chronic wound infection [22]. Quantative analysis (eg through wound biopsies). This can assist with the recognition of an increased bacterial burden; however, this is not regularly undertaken in the UK and previous studies have shown that wounds can heal despite high bacterial counts [23].

Treatment
Once a diagnosis of wound infection has been confirmed and antibiotic sensitivities identified, appropriate management regimens should be considered, with a high priority given to reducing the risk of cross infection. It is important to treat the patient as a whole and not the infection alone, so management strategies must be based on data derived from an holistic assessment of the needs of the individual [24]. The main treatment objective will be to reduce rather than eradicate the bacterial burden within the wound margins. In addition to antibiotic therapy, there are two main generic groups of wound management products that have the potential to reduce the bacterial burden in the wound, these are compounds containing silver or iodine [25]. Antibiotic therapy Antibiotics are chemical substances produced by a micro-organism that have the capacity, in dilute solutions, to selectively inhibit the growth of or to kill other microorganisms [11]. Whereas it is now generally accepted that systemic antibiotics are essential for the management of clinically infected wounds, the choice of antibiotic to be used is not always apparent. Only after a comprehensive assessment process including consideration of patient characteristics, the results of microbiological investigations and the identification of both the nature and location of the wound, can the most appropriate antibiotic be identified.

The routine use of topical antibiotics is not justified for colonised or infected wounds [26]. In addition, a recent systematic review of antimicrobial agents has concluded that systemic or topical antimicrobials are not generally indicated for the management of chronic wound infections [27]. However, there may be some value in the prophylactic use of topical antimicrobials for the initial management of acute cellulitus, whilst awaiting clarification of antibiotic sensitivity and the establishment of a therapeutic regimen. Resistance to antibiotics has become a serious problem in recent years particularly with the rise of epidemic strains of MRSA. The overuse of broad-spectrum antibiotics will only serve to exacerbate the situation. It could therefore be argued that all antibiotic use should be based on known sensitivities. Iodine Iodine is an element that has antiseptic properties. It is active against a number of pathogens. In the past its use has been limited by the fact that elemental iodine can be absorbed systemically, is almost insoluble and can be an irritant to the skin. In wound management iodine is used in two forms: Cadexomer iodine - a polysaccharide starch lattice containing 0.9% elemental iodine that is released on exposure to wound exudate. PVP-1 (Povidone iodine) - an iodophor composed of elemental iodine and a synthetic polymer

Both have different physical characteristics that relate to the component parts and the iodine concentration of available iodine that is released when in use. Clinically iodine is indicated for wound cleansing, wound bed preparation (the stimulation and influence of specific cells involved with the immune system) and the prevention and management of wound infection [28]. Silver Recently a number of dressings containing silver have become available, although silver and silver compounds have been routinely used in clinical practice as bactericidals for over a century. Silver interferes with the bacterial electron transport system and inhibits the multiplication of the bacteria. However, to achieve this, silver ions have to be able to enter a cell. The chemical bonding of silver with a sulphonamide antimicrobial sulphadiazine - has resulted in the development of a safe broad-spectrum agent for topical use (eg Flamazine). In this formulation silver is released slowly from the transport medium in concentrations that are selectively toxic to micro-organisms such as bacteria and fungi. This type of silver product has been used successfully in the management of acute and chronic wounds [11]. Products that can sustain the interaction of silver with micro-organisms in the exuding wound are likely to be more effective in preventing/controlling local infection as potentially more silver ions will be available to enter bacterial cells. This assumes that the concentration of silver in the solution is both correct and maintained. Further interventions Other appropriate wound management interventions that can be considered to help reduce the bacterial burden on the wound surface include autolytic or enzymatic debridement, surgical debridement, maggot therapy and the use of topical negative

pressure (TNP) for example, vacuum-assisted closure (VAC), in conjunction with the use of appropriate secondary dressings as required [29].

Summary
The importance of wound infections, in both economic and human terms, should not be underestimated. Practitioners need to know how to recognise and manage the signs and consequences of clinically infected wounds. The key principles for the management of a patient with a wound infection can be summarised as follows: Treat the patient holistically Recognise the signs of inflammation/increased bacterial burden/clinical infection Be able to take 'reliable' wound swabs Be able to interpret culture reports Treat the infection - causative organism(s) Consider antibiotic sensitivities Consider which wound management products are suitable and appropriate Minimize the risk of cross infection Reduce the risk of any complications Educate the patient and his/her family and carers

The incidence of wound infections will only be reduced over time if all practitioners keep these principles in mind when dealing with patients and plan interventions based on appropriate assessment techniques.

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