It has been estimated that 2.2 million wounds are treated in the UK each year, costing the NHS more than £5 billion (Guest et al, 2015). GP and nursing time accounts for the majority of the costs, but it is estimated that approximately £1.39 billion is spent on antibiotics. Many patients present with chronic wounds (about 60%) with some remaining unhealed after 12 months (Guest et al, 2017). Many conditions can predispose people to wounds that are difficult to heal and these can become chronic unless the underlying causes are addressed. As an example, people with diabetes have a high incidence of wounds on their feet, which can be hard to heal (Vowden, 2011).
Modern molecular techniques have shown that more than 80% of chronic wounds are colonised with biofilm (an aggregate of microorganisms embedded within a self-produced matrix of extracellular polymeric substances attached to the wound tissues) (Malone et al, 2017). Biofilm prevents healing (Wolcott et al, 2008), and has a protective function, which renders wounds unresponsive to topical and/or systemic antimicrobial treatment (Costerton et al, 1981).
Conversely, acute wounds usually heal without complication within 10 days and, if they become infected (approximately 5% depending on type and site) (Public Health England, 2019), they are usually infected with a single microorganism (Dowd et al 2008), which often responds to antibiotic treatment.
Most wound infections are caused by bacteria. Increasingly, common wound pathogens are becoming resistant to antibiotics and in the future we may have no antibiotics to treat severe infections (Howell-Jones et al, 2005). It is imperative that practitioners stop the unnecessary use of antibiotics, try alternative approaches to prevent and treat less severe infection and apply these principles to the use of topical antiseptics (Edwards-Jones, 2018).
Antimicrobial resistance (AMR) is causing concern globally and has become a priority for many health professionals. The World Health Organization (WHO) has issued a global action plan because it threatens ‘the very core of modern medicine as we know it’ (WHO, 2015). Effective antimicrobial agents are essential for protecting patients against infection from surgery and other infectious processes.
Unfortunately, misuse and overuse of antibiotics in human medicine and food production since they were introduced 70 years ago has created the current situation and has put everyone at risk. There is a dearth of new antibiotics and, if nothing is done to restrict the use of those that remain effective, there is a risk of returning to the pre-antibiotic era where simple infections could result in death. This necessitates immediate action and the implementation of antimicrobial stewardship in all healthcare professions as well as in food production and agriculture.
The WHO's action plan promotes coordination of sectors including human and veterinary medicine, agriculture, finance and environment, and well-informed consumers (WHO, 2015).
It is essential that all wound care practitioners prescribing, dispensing and using antimicrobial agents as systemic or topical treatments should be aware of their appropriate and inappropriate use. Normal treatment strategies include antibiotic treatment if there are systemic signs or cellulitis and topical antiseptic treatments within topical dressings or creams (Nicolle, 2014). It is therefore important that the use of antimicrobials in wound care is carefully monitored and, through good guidance and policies, is reviewed for various types of wounds.
Box 1 outlines types of antimicrobials and concerns about resistance.
The threat of AMR has led to the introduction of antimicrobial stewardship in the healthcare environment as well as in agriculture and the food industry.
Antimicrobial stewardship (AMS) is the organisational, system-wide approach to promoting and monitoring judicious use of antimicrobials to preserve their future effectiveness (Nathwani et al, 2012). The AMS principle in the clinical environment is to prescribe:
‘The right antibiotic, for the right patient, at the right time, with the right dose, and the right route, causing the least harm to the patient and future patients.’
As antimicrobial agents have been used indiscriminately since their introduction, changing prescribing practice will be difficult and require adherence to strict new guidance to effect any change. Effective stewardship programmes require both the necessary funding and staff educated to carry out the duties expected of them.
Within NHS acute hospital trust and primary care settings, there are dedicated teams of pharmacists, microbiologists, infection control officers, nurses (especially those who prescribe) and physicians. These teams require support from IT technical staff and administrators to produce the reports required for the programme to be effective. The stewards are clinically active and visible to frontline prescribers who pave the way for acceptance of their recommendations (BSAC, 2018).
Approaches to implementation are through: persuasive methods, with the aims of educating clinicians and encouraging optimal treatment; or by restrictive methods, which constrain what clinicians can prescribe by limiting access to specific antibiotic agents or by instituting automatic stop orders or time limits for antibiotic treatments (Wagner et al, 2014). Which method is the best for a particular organisation can be determined only through monitoring prescriber compliance.
Whatever implementation method is chosen, it should include local guidelines for prescribing antibiotics for the various conditions where infection may be involved. The AMS team will also put together guidance on prophylaxis, usually underpinned by NICE guidelines. (Nathwani, 2012).
The AMS team also produces reports on antibiotic use, breaking down information into details including on which type of antibiotic is used for which conditions. IT specialists who can abstract data, generate reports and build interfaces within the healthcare environment are essential to ensure successful stewardship going forward (BSAC, 2018).
Box 2 sets out the main steps for setting up and introducing an AMS programme.
Steps for success
There several key steps for success (Box 3). The AMS team will action and implement interventions, such as prospective audit and feedback, to improve antibiotic use. Their role also includes tracking and monitoring antibiotic prescribing, the effect of interventions and other important outcomes, such as impact on Clostridium difficile infections and resistance patterns and regularly reporting information on antibiotic use and resistance to prescribers, pharmacists, nurses and hospital leadership (Wagner et al, 2014).
Where AMS involves wound care, the appropriate tissue viability nurses, podiatrists and community nurses will have the necessary input into decision-making (Lipsky et al, 2016). It may also be prudent to educate patients on the importance of following guidance and on why AMS is essential for the future of antimicrobial therapy, especially in wound care where chronic wounds are numerous (Guest, 2017; Edwards-Jones and Spruce, 2019).
It is essential that education is ongoing and prescribers, pharmacists, nurses and patients are informed about current topics such as adverse reactions from antibiotics, antibiotic resistance and optimal prescribing (Davey et al, 2013). The AMS team can be consulted for prescribing advice and specific guidance can be tailored for specific problem patients. The aim of the AMS team is to achieve the best clinical outcome while minimising any potential toxicity using guidance and ongoing education (Lipsky et al, 2016).
Principles of AMS
Generally, AMS should eventually prevent: inappropriate antimicrobial prescribing when they are not indicated (for example when there is a non-infectious problem); prescribing the appropriate regimen when antimicrobial treatment is required; prescribing treatment for the correct duration; and prescribing an antimicrobial with minimal risk for the patient (in terms of adverse events) (Davey et al, 2013).
As prudent use of antimicrobial agents is now imperative and affects society at all levels, improving antibiotic use also increases accountability and transparency (Spellberg et al, 2016).
The golden rule of antimicrobial prescribing is described using the Mind Me mnemonic:
In wound care, empirical antibiotic therapy in the absence of a definitive diagnostic test is still recommended if there are signs of local wound infection, while the use of topical antimicrobial agents and non-medicated interventions are still being widely debated. Antibiotics are commonly prescribed for skin and soft tissue infections, but published guidance on treating these is limited (Dryden et al, 2011). Recent research into antibiotic prescribing in GP services has shown that more than one third of patients attending GP services in the UK are prescribed antibiotics and that approximately 16% of these are prescribed to those with a wound infection (Dolk et al, 2018). One retrospective study in Norway showed that most patients in primary care with wounds were given antibiotics inappropriately (Gürgen, 2014). These studies demonstrate that many antibiotics in the community and primary care are prescribed unnecessarily and implementing AMS policies should help to reduce this usage.
Chronic wound infections are frequently polymicrobial so require broad-spectrum antimicrobial regimens, and many of these wounds take many weeks (or even months) to heal. Furthermore, because wounds are frequently recurrently infected, these patients are often exposed to repeated courses of therapy. It is probable that these repeated doses of antibiotics could lead to antibiotic resistance and perhaps a better approach would be biofilm-based wound care (Wolcott and Rhoads, 2008; Atkin et al, 2018). Biofilm-based wound care is promoted for chronic wounds to reduce bioburden and disrupt the biofilm by a continual cycle of regular debridement and cleaning, followed by applying a dressing that is either an antiseptic dressing or a non-medicated dressing that removes the bioburden. Following this regimen, it is hoped, will move the static wound onto healing (Malone and Swanson, 2017). Dressings are chosen by the clinician based on the needs of the patient and their individual wound management plan.
Antimicrobial wound dressings may be an appropriate choice following biofilm-based wound care. However, before prescribing any wound products or medications, the clinician must undertake and document a holistic assessment of the patient. This approach is described in Wounds UK's (2013)Best Practice Statement. The Use of Topical Antimicrobial Agents in Wound Management. This document outlines the topical antimicrobial dressings available and how to use them appropriately, including when to start and stop using them. It is inappropriate to continue using these dressings if there is no benefit to wound healing; their use should be reviewed regularly; fortnightly is recommended.
Products vary according to the concentration and availability of the active ingredients, their mode and duration of action, and their ability to handle exudate, odour or pain, and should be selected specific to the needs of each wound. Biofilm-based care of chronic wounds, with several cycles of cleaning, debriding and dressing with topical antiseptics should reduce bioburden and negate the need of antibiotics.
Hopefully, bedside tests (such as lateral flow devices) that can quantify markers in the wound bed that are either raised or inhibited may become available to help with decision making. A device that determines protease levels in the wound bed which correlate with chronic inflammation is available; the Woundchek Protease Status (Woundchek Laboratories) is an in-vitro diagnostic colour-change test for the qualitative assessment of human neutrophil-derived inflammatory protease. Using a device like this can help with decision making as it can indicate whether the wound is not healing because of high levels of protease or other factors. Protease levels are a good surrogate marker for remnant wound biofilm and can indicate the amount of active biofilm present in a wound (Wolcott and Rhoads, 2008; Wounds International; 2011).
AMS for patients with wounds
A European Wound Management Association position document in 2016 proposed a simplified algorithmic approach to prescribing antimicrobial therapy for wounds (Lipsky et al, 2016)(Figure 1).
The basis of treatment of a wound with antimicrobials should be underpinned with microbial culture. It is important to identify the wound pathogen through its isolation from a sample through swabbing or biopsy (Lipsky et al, 2016). Acute wounds tend to be infected with a single pathogen (James et al, 2008) so taking a wound swab for pathogen identification and antibiotic susceptibility testing will allow the correct antibiotic to be administered. Empirical antibiotic treatment should be given and changed to a narrow spectrum antibiotic once the results are available (Lipsky et al, 2016). Diagnosis of infection in a chronic wound is more difficult as there are often multiple microorganisms present growing in a biofilm on the wound surface. Their pathogenicity is confounded because different microorganisms interact (Malone et al, 2017).
Current guidance states that a wound should be treated with antibiotics if a laboratory reports the presence of a pathogen and there are clinical signs of infection. As there is no other diagnostic tool to confirm whether there is a infection in the wound at the point of care, this approach to wound management should be continued. It is vital to stop unnecessary use of antibiotics and topical antimicrobials so it is essential that a point of care diagnosis tool is developed. While microbial culture is the traditional and still the commonest method for laboratory diagnosis, newer molecular microbiological techniques are becoming more commonplace in laboratories and often disclose more pathogens than standard cultures in chronic wound swabs (Wolcott et al, 2016a). These probably reflect a polymicrobial community as seen in a biofilm.
Usually, a broad-spectrum antibiotic is administered as empirical therapy and changed to a narrow-spectrum agent when a report becomes available (Lipsky et al, 2016). Key factors for selecting empirical antibiotic treatment include the severity of infection, any history suggesting likely pathogens (eg exposure to animals, recent travel or recent admission to a healthcare facility) and recent antibiotic therapy (Leekha et al, 2011). Infected wounds containing Staphylococcus aureus are almost always prescribed antibiotics, usually with flucloxacillin as the drug of choice. Generic guidelines are available for a number of different conditions, for example MRSA (Liu et al, 2011) and skin and soft tissue infections (Stevens et al, 2014) and are amended to suit different circumstances and in the light of local antibiotic resistance data and the institution's AMS strategy (Leekha et al, 2011).
Laboratories routinely report antibiotic susceptibilities for pathogens and do not test or report susceptibilities for topical antiseptics even though they are more commonly used. This is because most topical antiseptics used in wound care are broad spectrum, affecting most common wound pathogens, and most laboratories are not set up to test for them.
A few topical antibiotics (eg fusidic acid, mupirocin and neomycin) may be appropriate to treat localised acute superficial skin infections, such as impetigo and folliculitis, but almost all other clinically infected wounds require systemic antibiotic therapy and any use of topical antibiotic is discouraged (Wilkinson, 1998). Topical metronidazole may be beneficial in reducing wound odour and should be used only in fungating wounds, but the evidence is weak (Castro and Santos, 2015).
Non-antibiotic antimicrobials are widely used in wound care but data supporting their usefulness for treatment is limited. These non-antibiotic antimicrobials may reduce bacterial numbers in the wound, which will help wound healing. These include antiseptics (eg chlorhexidine, povidone and cadexomer iodine, and polyhexamethylene biguanide), heavy metals (eg silver, mercury and mercurochrome) and natural products (eg honey).
Investigators are now seeking non-antibiotic approaches to reducing and/or killing bacteria in wounds. New products for the prevention and treatment of topical infection include non-medicated dressings that remove devitalised tissue (Anghel et al, 2016; Pilcher, 2016), and hydrocolloids and hydrogels are good examples of dressings that provide a moist wound environment and also help to debride the wound (Atkin and Rippon, 2016).
Bacteria can also be removed from the wound bed through sequestration (removal and retention of the bacteria within the dressing) (Rippon et al, 2018). The ability to do this varies between dressing types and depends on the fibres they use (Edwards-Jones et al, 2014). Additionally, new dressings that can remove and retain bacteria through chemical interaction are now available. Often, these dressings are coated with a chemical or the fibres themselves may cause the effect. Examples are dressings where dialkylcarbamoylchloride (a fatty acid) is coated on an open mesh dressing and binds to bacteria using a hydrophobic interaction (Cooper and Jenkins, 2016; Totty et al, 2017).
Conclusion
Because of the concerns over AMR combined with the lack of new antibiotics in the future, practitioners have a responsibility to reduce the unnecessary use and misuse of all antimicrobials wherever possible. Currently, the focus is on antibiotic use, but AMS must cut across boundaries in wound care and practitioners must start to use the plethora of wound care products effectively.
The presence of bacteria in wounds can have a detrimental effect on healing and practitioners need to reduce bacterial numbers effectively, possibly through using the properties of dressings and good wound management.
Biofilm-based wound care has been suggested as a means of reducing bacterial burden in chronic, non-healing wounds and this can be achieved with various methods of debridement and cleaning, followed by the application of a modern wound dressing (which may or may not contain topical antiseptics).
All people who manage wounds should be more educated in this area and their understanding of new wound care products improved to build their confidence and move away from using antibiotics when they are not necessary.