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Effective use of antimicrobials for chronic wounds

Sylvia Stanway
Lead Nurse for Tissue Viability
Salford Primary Care Trust

There are over 600 wound care products in the current British National Formulary (BNF) and it is estimated that antimicrobial wound dressings cost the NHS over £30m per year.1,2

Bacteria contaminate all chronic wounds. We have bacteria on our skin all the time and these inevitably transfer themselves to open wounds. Healing can occur even in the presence of bacteria and if a wound is swabbed it will frequently grow several species of bacteria, not all of which will be harmful, and not all of which will need treatment.

Many nurses may not understand the way in which microbiologists differentiate between various bacteria. They hear the terms but do not always comprehend what they mean. Bacteria can be differentiated into gram-positive or gram-negative by testing them with the "gram stain". The stain attaches to part of the bacterial cell wall called peptidoglycan and causes a purple colouration (gram-positive) under the microscope. Those that are negative do not retain the stain and are pink. Early chronic wounds contain mostly gram-positive bacteria. Wounds of several months' duration will have, on average, four to five microbial pathogens, including anaerobes, some of which are gram-negative.

It is important that we treat the clinical signs of infection and not the swab result we receive. The bacteria itemised on the swab may not be the causative organism or there may not be enough of them to be causing a problem. We look for the cardinal signs of infection, such as heat, redness, swelling, pain and exudates, but also less obvious signs such as pocketing, friable granulation tissue, an increase in exudate levels or an increase in pain.3,4 Anecdotally, certain bacteria appear to aid wound healing, although there is no evidence to prove this.

There is also some confusion over the infection continuum.5 What is wound contamination? Simply put, it is the presence of nonmultiplying bacteria on the wound bed. Colonisation consists of multiplying bacteria without causing damage to the host. Critical colonisation presents when these multiplying bacteria begin to produce toxins and in some way slow or prevent the wound from healing. This critical colonisation is the state that is usually treated with antimicrobial dressings. Infection is present when multiplying bacteria produce toxins or waste products that damage the host. This final stage is usually managed with systemic antibiotics.

How does the wound progress from colonisation to infection? There appear to be several factors involved, which include the dose (the number of organisms involved), virulence (the strength or toxic nature factors they produce) and the host resistance.6 Examples of virulence factors are hyaluronidase (Streptococcus pyogenes), proteases (Staphylococcus aureus, Pseudomonas aeruginosa), toxins (Streptococcus pyogenes, Staphylococcus aureus) and endotoxin (gram-negative organisms). Some organisms produce few virulence factors. However, synergy between different bacterial factors can cause host damage, eg, group B streptococcus and S aureus - the synergy between the two toxins results in hemolysis.

Identifying an infected wound
The infection continuum and the clinical signs are there to help, but there is no foolproof laboratory test that will tell you if a wound is infected. However, there is one feature that is common to all infected chronic wounds – the failure of the wound to heal, followed by a progressive deterioration. The typical features of wound infections are:

  • Increased exudates.
  • Increased swelling.
  • Increased erythema.
  • Increased pain.
  • Increased local temperature.
  • Periwound cellulitis, ascending infection, change in appearance of granulation tissue (discolouration, prone to bleed, highly friable).4

Many chronic wounds support relatively stable mixed communities of microorganisms without causing detrimental effects in the wound itself. Systemic antibiotics are not always indicated in case of infection and it is always worth discussing with the microbiologist if you are unsure.

Topical antimicrobials may deal with the problem adequately or in combination with antibiotics. However, in cases of systemic infection, antibiotics should always be considered. Many NHS trusts have specific protocols for antibiotic prescribing for diabetic foot infections or cellulitis. Antibiotics are not indicated simply to limit microbial numbers in uninfected wounds or as prophylaxis, unless advised by a specialist nurse, medical practitioner or local protocol.

It is always difficult to determine which antibiotic needs to be prescribed. The swab result may indicate a certain antibiotic, but it should always be remembered that the bacteria picked up by the swab might not be the bacteria that's causing the problem. Frequently, in community care we find ourselves prescribing broad-spectrum antibiotics to try to cover all bases. It may be more advisable to give shorter courses of targeted antibiotics than seven days of broad spectrum. With the increase in the numbers of C difficile cases, infection control nurses are also beginning to produce guidelines about antibiotic use. This has led to the increasing use of topical antimicrobials in wound dressings.

How useful are topical antimicrobials?
There have been some reports of tissue toxicity and resistance to topical antimicrobials. There is an increasing feeling that there is an overuse of antimicrobial dressings. However, this may be due to medical professionals using them for excessively prolonged periods of treatment, as opposed to use on too many patients.

Most trusts now have a protocol for antimicrobial use and, although it is not universal, this is the format that is generally agreed on: review after two weeks' use and, if indicated, stop or continue for a further period – not exceeding four weeks in total. Failure to respond in four weeks requires careful reassessment, in line with antibiotic guidelines. Selecting the correct antimicrobial is also difficult. However, criteria have been suggested that help choice.7,8 They include:

  • Specificity (is the agent active against the specific bacteria causing the problem in the wound?).
  • Efficacy (does the dressing work? For example, are there sufficient levels of the agent to achieve bacterial kill as opposed to bacterial inhibition, and does it do this quickly?).
  • Cytotoxicity (is the dressing likely to damage healthy cells?).
  • Allergenicity (does the dressing contain any materials likely to cause sensitivity or allergy?).

A systematic review of the use of topical antimicrobials in chronic wounds did not make any recommendations. This was because the trials were considered to be of poor quality. In 2006, Maillard and Denyer suggested that there were criteria that could be applied to an ideal antimicrobial dressing.9
These included:

  • Provides sustained antimicrobial activity.
  • Provides a moist wound-healing environment.
  • Allows consistent delivery of the antimicrobial
  • in the dressing over the entire surface of the wound.
  • Allows monitoring of the wound with minimum interference.
  • Manages exudate if this is a problem.
  • Is comfortable.
  • Provides an effective microbial barrier.
  • Absorbs and retains bacteria.
  • Avoids wound trauma on removal.

What types of antimicrobial dressings are available?
There are many types of antimicrobial dressings, which can be classified into several groups as follows.

Honey was used by the Egyptians in wound dressings. The evidence of antibacterial activity is extensive. Some types of honey are bactericidal against methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE). Several types are now available as sterile wound dressings - not just manuka honey. However, it must be medical-grade honey and not the breakfast table variety.

Osmorlarity, acidity and the generation of hydrogen peroxide on dilution are all suggested as contributing to the antimicrobial potency of honey dressings. There is no clear evidence if this is true. There are no standardised protocols for the frequency with which honey should be applied and the type of secondary dressing that should be used.10,11 As a result of their ability to attract fluid by osmosis, honey dressings can increase exudate levels dramatically.

Hydrogen peroxide
Hydrogen peroxide is antiseptic and disinfectant and was historically used as a 3% (10 volumes) or 6% (20 volumes) aqueous solution to clean necrotic, infected wounds. It 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. A very low concentration is available as an end product in dressings such as Flaminal (Ark Therapeutics) and Oxyzyme (Archimed).

Iodine is an element that was discovered in 1811. Its first reported use in treating wounds was by Davies in 1839. It can sting or burn on open skin. The development of povidone iodine and cadexomer iodine (a three-dimensional starch lattice containing iodine) since 1949 has given safer, less painful varieties. It is a very useful and safe bacteriostatic, and is bactericidal and active against MRSA.

There is very limited or no evidence of the emergence of iodine-resistant strains. Iodine products can cause thyroid disruption. Patients with a history of a thyroid disorder should have their thyroid function reviewed before and during treatment and while using the product. Iodine dressings have a maximum dosage that may be used at any one time and a maximum length of time over which they can be used (see BNF).2 The dressing changes colour from deep yellow to white as the iodine is used, clearly showing when the antimicrobial activity is exhausted.

Ancient dynasties in the Middle East and South America used silver to purify drinking water. Ambrose Paré (1517–1590), a French surgeon, used silver clips in facial reconstruction, and William Halstead (1895, American) used silver wire sutures in hernia repairs. Pasteur and Koch discussed silver nitrate as an antiseptic in the 1880s. Several authors have described its effectiveness in wound dressings and catheters.12,13

Silver ions interact with bacterial DNA inhibiting cell division. They also interfere with normal function of the bacterial cell causing the cell to shut down and die and bind to and destroy the cell wall. Efficacy has been evaluated mainly in vitro.14,15 Recent studies have provided detailed information on bacterial sensitivity and mechanisms of action. There has been an explanation given as to why certain bacteria are susceptible and others are resistant by certain authors.16

Allergy is associated with occupational exposure (silver workers) and silver jewellery. Prolonged and heavy contact can produce benign permanent discolouration of the tissues (argyia). There are no details of the number of people who are allergic to silver in dressings but patients should be made aware of the risk. Silver is contained in modern dressings in a controlled release form. Nanocrystalline dressings are effective barriers to bacteria and several silver impregnated dressings are bactericidal for epidemic MRSA. It is important to remember to remove silver dressings before a patient undergoes an MR scan as some have been shown to cause pain and burns.

Chlorhexidine compounds
These compounds are useful skin antiseptics and bind to the stratum corneum. They have a persisting activity, for at least six hours after application. 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.

Polyhexamethylene biguanide (PHMB)
PHMB has been used successfully since 1959 in surface disinfectants, eg, contact lens cleaning solutions, perioperative cleansing solutions and for breweries and swimming pools. It exerts little toxicity and has been in general use for approximately 60 years with no evidence of the development of resistance.

PHMB has previously been demonstrated to block Pseudomonas aeruginosa-induced infection and prevent its degradation of wound fluid and skin proteins in vitro.17 It can also kill a diverse range of bacteria and fungi. PHMB is a synthetic compound, which is structurally similar to naturally occurring antimicrobial peptides (AMPs). AMPs are produced by the majority of living organisms and have a broad spectrum of activity against bacteria, viruses and fungi.17 AMPs are positively-charged molecules that bind to bacterial cell membranes and induce cell lysis by destroying membrane integrity, in a similar way to penicillin and cephalosporin antibiotics. The structural similarities between AMPs and PHMB mean that the latter can insert into bacterial cell membranes and kill bacteria in a similar way to AMPs.17 There are other antimicrobials available and all are useful.

[[Pract pointers wounds]]

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