Can a wound dressing colour change indicate infection?

wound  dressing

For many years, diagnostic labs have used colour change as a marker for the growth of specific microbes. Think of all those chromogeneic agar plates that your lab goes through each day. And there are all sorts of broths that change colour in response to specific chemical changes caused by microbial growth. One of the first projects I was ever involved with was environmental sampling for MRSA at Lewisham hospital, where we used a selective broth that turned bright yellow when MRSA was present. So in a way, it is surprising that this approach has not been adopted as a marker to indicate wound infection.

Scientists at Bath Uni have developed a neat novel wound dressing that fluoresces when the early signs of an infection are present. The concept is simple: a gel containing tiny sacs of dye are included in a hydrogel dressing; if cytotoxins that are indicative of bacterial infection are present, they lyse the sacs and release the dye, which fluoresces under UV light.

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Should every body have a silver lining (inside and out)?

silver lining

sense about science

sense about science have asked me to meet one of their ‘Ask for Evidence’* requests about ‘Silver Shield’.

‘Silver Shield’ comes in two forms. A gel for topical application on wounds and an oral suspension. It seems that these two products are different formulations of the same biocide. It is true that silver has long been known to have antimicrobial properties, which is, of course, dose dependent. There’s a big difference in whether you apply the silver-containing gel to a wound versus drinking a silver-containing oral suspension in the hope of preventing or treating an infection.

There is some evidence that topical application of silver can help to disinfect wounds, which improves their healing. A number of well-designed randomised controlled studies have shown that silver containing dressings can help to improve wound healing. However, there is less evidence for gels (such as Silver Shield), and most literature is restricted to burns.

The real problem with claims around these products relate to the oral suspension. The audio recording on the website includes detailed dosing information for the oral suspension to prevent and treat MRSA wounds. There is no evidence to my knowledge in the peer-reviewed literature that ingesting an oral suspension of silver confers any health benefit for the prevention or treatment of MRSA or any other microbial infections. The product claims to be ‘non-toxic’ but there is some evidence of toxicity through ingesting silver suspensions in animal models.

The patent includes some laboratory (in vitro) data showing that silver inactivates a range of microbes, which is already known from other studies. It also references a number of case series of patients who took an oral suspension and recovered from various conditions. Details on these patients are scant, and there is no mention of a placebo control group, which is necessary to determine whether improvements were really due to the treatment or explained wholly or in part by the natural disease progression or a placebo effect. Indeed, the ‘case report’ for HIV betrays a frightening lack of understanding: to claim that a 5 day course of oral silver suspension can ‘resolve’ HIV is utterly scandalous:

‘Retrovirus Infection (HIV). The method comprises the step of administering a silver composition, comprising 5 to 40 ppm silver one to five times a day orally area until there was a response. One patient exhibiting HIV (human immunodeficiency virus) was treated with about 5 ml (approximately one teaspoon) of a composition of the present invention two times per day. The patient’s symptoms resolved within five days.’

As we come towards the end of antibiotics, we need to open our eyes to the potential of non-antibiotic treatments, and silver-based wound gels and dressings are a promising candidate. However, more evidence is required before widespread adoption of Silver Shield gel. As for taking an oral suspension of silver to prevent and treat microbial infections: this is likely to cause more harm than good and toxicity studies are required before considering testing this product on humans, let alone buying it online for £19.95!

*Sense about science ‘Ask for Evidence’ campaign:

ask for evidence

Every day, we hear claims about what is good for our health, bad for the environment, how to improve education, cut crime and treat disease. Some are based on reliable evidence and scientific rigor. Many are not. These claims can’t be regulated; every time one is debunked another pops up – like a game of whack-a-mole. So how can we make companies, politicians, commentators and official bodies accountable for the claims they make? If they want us to vote for them, believe them, or buy their products, then we should ask for evidence. Read about our Ask for Evidence campaign.

Image: ‘Silver lining’ by Bruce Turner.

Chronic wound? No problem – a splash of oxygen peroxide should do the trick


I was involved in a recently published RCT of a novel wound care system (‘BioxyQuell’), which trailed the application of an aqueous oxygen peroxide (AOP, aka aqueous ozone) lavage on venous leg ulcers. The study isn’t perfect, but the results are encouraging and should serve as a basis for further evaluations.

The RCT was performed in the community setting. Sixty-one patients were enrolled if they had chronic venous leg ulcers, and randomised to either 6 AOP treatments or sham placebo treatments with sterile water over 2 weeks. AOP and placebo arms were both treated with standard-of-care compression bandaging between treatments and for the duration of the study. Patients who completed the initial 8 week RCT were enrolled into a follow-up study evaluating wound healing at 12 weeks, 6 and 12 months. The key results are:

  • No significant difference in wound healing at 8 weeks (the primary outcome). But, something surprising happened during the follow-up study: every single one of the AOP treated patients had healed by 12 months vs. 50% in the placebo arm (Figure 1). Could it really be that a 2 week AOP treatment period has such a remarkable impact on long-term wound healing? It’s just about plausible if there was some pretty fundamental change to the wound bed. But I’d need to see some more data to be convinced!
  • Almost 50% of patients in the placebo arm were healed by 8 weeks. The inclusion criteria required a chronic leg ulcer more than 3 months old, so why did 50% of placebo patients heal? I suspect the answer lies in good compression bandaging, which was mandated during the trial. There’s a temptation to apply the bandages too loosely to be effective to improve patient comfort.
  • AOP patients were significantly less likely to be withdrawn from the study due to wound infection during the first 4 weeks of the RCT (Figure 2). This stark difference makes sense: AOP is a biocide with the capacity to dismantle biofilms, which are involved in wound infection.
  • Pain and bacterial contamination were significantly lower in the AOP arm during the treatment phase. Wound size was also significantly reduced in the AOP arm when accounting for patients with deteriorating infected wounds.

Figure 1: Wound healing in the AOP and placebo arm during the RCT (up to 8 weeks) and follow-up study (up to 12 months).

BxQ healing

Figure 2: Patient withdrawals due to wound infection during the first 8 weeks of the RCT.

BxQ withdrawal

As ever, the study raises as many if not more questions than it answers:

  • What is the optimal treatment regimen for AOP? Is two weeks enough? Is three treatments per week about right (and feasible)? Put another way, how would this study have looked if the AOP treatment was performed for 4 weeks instead of 2? The fact that improvements in wound size reduction, pain, bacterial contamination and withdrawal due to wound infection trailed off after the 2 week treatment period indicates that a longer treatment period should be explored.
  • What is the best application of AOP in healthcare? Acute care? Primary care? Trauma? Diabetic foot?
  • Is ‘wound healing’ the right outcome measure? Perhaps prevention of withdrawals due to wound infection is the most important finding of this study. And don’t underestimate the value of the reduced pain in the AOP arm – the ulcers are very painful and make sufferers pretty miserable!

This was a fair sized randomised, sham placebo controlled, double blinded study performed with tight inclusion and exclusion criteria in the community setting. This sort of RCT is surprisingly rare in the wound care literature. However, it was terminated early (due to lack of significant difference in wound healing and the fact that it took years to recruit a decent number of patients) and the primary outcome (wound healing at 8 weeks) was non-significant. Nonetheless, wound size, pain and bacterial contamination were reduced by AOP treatment, the long-term reductions in wound healing are tantalizing, and reduced withdrawals due to wound infection are tangible.

Article citation: O’Halloran PD, Winter PK, Otter JA, Adams NM, Chewins J. Aqueous oxygen peroxide treatment of VLUs in a primary care-based randomised, doubleblind, placebo-controlled trial. J Wound Care 2014;23:176-90.

Post script: in memoriam

The statistician who formulated and executed the statistical analysis for this study, Carla White, sadly died (too young) during the latter stages of getting this article published. I am sorry not to have the opportunity to work with her again.