The Silver Bullet

1 October 2008 (Last Updated October 1st, 2008 18:30)

Increasing use of antimicrobial dressings in wound care has prompted further examination of the viability of silver. How does it compare to other widely used healing methods? Richard White of the University of Worcester investigates.

The Silver Bullet

In the short course of the 21st century the dominant trend in wound management has been towards the use of topical antimicrobial dressings. This reflects a greater understanding of wound microbiology and the role bacteria play in wound pathology, particularly in the so-called 'chronic' wounds such as leg ulcers, pressure ulcers and diabetic foot ulcers. Together these three types of wounds account for approximately £4bn of the UK's NHS expenditure.

Any 'wound watcher' will over the past 30 years have noticed distinct trends in strategies of wound management and of product usage. First came the moist wound healing revolution, heralded by thin films; later followed hydrocolloids, alginates, topical negative pressure and soft-silicone technology.

Most recently, the considerable use, and expenditure, on antimicrobial dressings has focused the attention of purchasers on the wound care budget. However, this appears to be regardless of any subsequent increase in morbidity attributable to wound infection. Wound management in the UK is predominantly a nurse-led discipline. It is also, with respect to chronic wounds, a largely primary care function. It is no coincidence that the advent of moist wound healing and its attendant product developments is contemporaneous with the tissue viability clinical nurse speciality.

While sales figures of dressings are not generally made publicly available, the antimicrobial dressings market in the UK is currently worth at least £30m (extrapolated from 2006 IMS data). The bulk of this (approximately £27m) is attributable to silver dressings, with iodine, honey and a variety of other agents making up the rest. In relation to the drugs budget in any acute or primary care trust, the dressings expenditure is minuscule, accounting for no more than 5% at most, yet it is this expenditure that has come under close scrutiny in recent months.

There is an implication that because the expenditure on silver dressings has increased dramatically over the past ten years, that such dressings are being overused. However, there is no objective evidence to this effect. Criticisms have been levelled at the quality of clinical evidence available for silver dressings, implying that they are not well-supported in this respect. Examining the role and value of topical antimicrobial dressings and their supporting evidence can offer a judgement to
guide future clinical practice.

Diagnosis of wound infection

The appropriate clinical usage of antimicrobial dressings is essential for efficacy, and for cost benefit. Typically, such dressings are indicated for wounds exhibiting signs of local infection or of critical colonisation. Unless patients are designated 'at risk' prophylaxis is not appropriate. The justification for initiating or continuing dressing use must be based on clinical judgement, as must the decision to stop.

This latter point has become controversial; overuse of antimicrobial dressings is most probably due to excessively prolonged periods of treatment as opposed to use on too many patients, therefore, appropriate treatment duration becomes crucial to health economic success. Research does not help in this respect as the necessary studies have not been conducted or published. As a guideline it is reasonable to objectively evaluate treatment success after two weeks' use, and, if indicated stop or continue for a further period – not exceeding four weeks total. Failure to respond in four weeks requires careful reassessment, in line with antibiotic guidelines which stop and assess earlier.

The current standard of wound infection criteria are those of Cutting and Harding. They have been validated by Gardner et al who found increasing pain and wound breakdown to be the most sensitive indicators of wound infection. All involved in wound management should bear these in mind at each assessment.

Classic signs of infection:

Signs of infection include pain, erythema, oedema, heat and purulence. Systemic signs of infection such as elevated white cell count (neutropenia) and elevated serum C-reactive protein (CRP) are standard blood measurements for infection. However, for chronic infected wounds such as leg ulcers, elevated CRP may not be diagnostic.

Topical antimicrobial treatments have been used for many years to control the wound bioburden, and to manage local infection. Trends in practice have changed markedly over recent years. Topical antibiotics have fallen out of favour, largely due to resistance and to frequent allergic contact dermatitis. However, narrow-spectrum antibiotics such as mupirocin and metronidazole are still indicated for topical use in specific indications. The use of antimicrobials (non-antibiotic) has increased, especially in dressing forms.

Antiseptics

At one time it was considered that the development of resistance to antiseptics and disinfectants was remote, but this has been shown to be inaccurate. Certain species, such as bacterial spores, mycobacteria and gram negative bacteria, possess intrinsic resistance, but plasmid-mediated acquired resistance to antiseptics and disinfectants has been described. For many, the use of antiseptics in wound care is biased by the understandable 'bad press' given to Eusol (Edinburgh University solution of lime) and the confusion over iodine compounds. The advent of modern, safe and effective antimicrobial dressings has proved invaluable to those responsible for wound care.

Silver

Silver and silver compounds have been routinely used as bactericidal agents for over a century. Silver is generally recognised as a safe, broad spectrum agent, with only irritation and skin discolouration (argyria) reported. Silver nitrate was probably the first silver compound used on wounds where it has an astringent and irritating effect; because of these problems and lack of evidence it is rarely used today.

"The appropriate clinical usage of antimicrobial dressings is essential for efficacy, and for cost benefit."

Silver sulfadiazine (SSD) is a broad-spectrum agent for topical use, usually as an oil-in-water cream formulation in concentrations that are selectively toxic to bacteria and fungi. Best known as the Flamazine 1% cream, SSD has been a mainstay of topical burns therapy and has been used successfully in acute and chronic wounds to treat infection. Resistance to SSD has been reported but is rare. However, allergic contact dermatitis is less so.

The way silver is incorporated into a dressing and how it interacts with microorganisms makes it suitable: its bioavailability is critical in determining its antimicrobial efficiency and its safety. Acticoat (Smith & Nephew UK) is an antimicrobial dressing that has also been shown to be effective against a wide range of organisms. The Acticoat range now has considerable clinical evidence to support its use in burns. Aquacel Ag (ConvaTec) hydrofibre dressing also has strong supporting in vitro and clinical evidence.

These two ranges have about 75% of the UK silver dressings market share.

Iodine

Alcoholic tinctures of iodine and iodoform have limited value in modern wound care because of the pain and staining that they cause. The development of povidone-iodine (a polyvinyl pyrrolidone surfactant/iodine complex or PVP-I) in 1949 and later cadexomer (a three dimensional starch lattice containing iodine) has provided safer, less painful alternatives that function by the sustained release of free iodine.

The efficacy of PVP-I as a pre-surgical skin antiseptic is unquestioned, but its value in wound care has been extensively debated. Iodine, as PVP-I or cadexomer, is a very useful and safe bacteriostatic and bactericidal agent active against MRSA and other pathogens. Unlike other antimicrobial agents with a long history of usage, there is limited evidence of the emergence of iodine-resistant strains. The non-specific mode of action of iodine in affecting multiple cellular functions probably accounts for this outcome.

Proflavine

An acridine derivative (originally used in dyes) is available as a cream, solution, and as a gauze soak. The latter is widely used as a surgical wound packing even though it has been found to be inferior to alginate dressing in this respect. There is no reliable evidence that proflavine gauze is effective, or that it has any clinical benefits. Indeed, the use of this combination in packing cavity wounds is of no proven clinical worth.

Chlorhexidine compounds

These are useful antiseptics for skin, being highly effective for hand washing and surgical scrub. They bind to the stratum corneum and have a persisting activity, remaining active for at least six hours after application. The acetate is intended for wound irrigation.

The gluconate is active against gram-negative organisms such as P. aeruginosa and gram-positives such as S. aureus and E. coli. Their toxicity and use on wounds has not been established categorically, although they may be a useful therapeutic option as an agent for topical use.

"The way silver is incorporated into a dressing and how it interacts with micro-organisms makes it suitable."

Hydrogen peroxide

Historically used as a 3% (ten volumes) or 6% (20 volumes) aqueous solution to clean necrotic, infected wounds, hydrogen peroxide is antiseptic due to the release of oxygen, an oxidising agent, on contact with the tissues.

There are safety concerns about using hydrogen peroxide solutions on open wounds, although dilute solutions are effective in the hands of experienced clinicians. Hydrogen peroxide at very low concentration is also available as an end product from dressings such as Flaminal (Ark Therapeutics) and Oxyzyme (Archimed).

Potassium permanganate

Weak solutions of this oxidising agent (one part in 5,000 to one in 10,000) are used as soaks to cleanse and deodorise eczematous wounds and leg ulcers. Although favoured by dermatologists, there is no objective evidence published to support their use in wound management. Environmental and toxicity issues dictate that their use on wounds should be avoided wherever possible.

Honey

Honey is an ancient wound remedy accredited with many curative properties. Antibacterial activity has been demonstrated by numerous in vitro studies. Clinical evidence is from case studies, cohort studies and clinical trials. Mechanisms by which honey influences the healing process are not yet fully explained, but are known to involve anti-inflammatory and antimicrobial actions.

Sequestration

Recent evidence indicates that an important infection control mechanism of certain wound dressings is the binding or sequestration of bacteria. For example, Cutimed Sorbact (BSN) is demonstrated to remove significant bacteria numbers through this mechanism. One distinct advantage is the absence of any possible resistance mechanism.

Eusol

Following the long public debate over Edinburgh University Solution of Lime about 20 years ago, most clinicians correctly decided to abandon the use of this agent. However, there are a number of backwaters where it is still used. On the face of the evidence, the continuing use of Eusol is unjustified.

Antimicrobials: the way forward?

The involvement of micro-organisms (particularly bacteria) in the wound healing process is of fundamental importance, even though a comprehensive explanation of their contribution is not yet available. Wound infection and critical colonisation not only interrupt the healing process, but have undesirable consequences in terms of patient discomfort, extended duration of treatment, increased management costs and possible mortality.

It is paramount that the risk of infection is minimised, and that management strategies maximise the potential of antimicrobial agents by the judicial use of antibiotics and antimicrobial dressings, without indiscriminate use and abuse.

Research material has been referenced in this text. For full details please contact the editor, [email protected]