Biofilm is the predominant mode of life for bacteria and today it is implicated in numerous human diseases. A growing body of scientific and clinical

Nitric oxide (NO) is a free radical of the human innate immune response to invading pathogens. NO, produced by nitric oxide synthases (NOSs), is used by the immune system to kill microorganisms encapsulated within phagosomes via protein and DNA disruption. Owing to its ability to disperse biofilm-bound microorganisms, penetrate the biofilm matrix, and act as a signal molecule, NO may also be effective as an antibiofilm agent. NO can be considered an underappreciated antimicrobial that could be levied against infected, at-risk, and hard-to-heal wounds due to the inherent lack of bacterial resistance, and tolerance by human tissues. NO produced within a wound dressing may be an effective method of disrupting biofilms and killing microorganisms in hard-to-heal wounds such as diabetic foot ulcers, venous leg ulcers, and pressure injuries. We have conducted a narrative review of the evidence underlying the key antimicrobial and antibiofilm mechanisms of action of NO for it to serve as an exogenously-produced antimicrobial agent in dressings used in the treatment of hard-to-heal wounds.

Biofilm development in wounds is now acknowledged to be a precursor to infection and a cause of delayed healing. A next-generation antibiofilm carboxymethylcellulose silver-containing wound dressing (NGAD) has been developed to disrupt and kill biofilm microorganisms. Thisin vitrostudy aimed to compare its effectiveness against various existing wound dressings and examine its mode of action. A number of biofilm models of increasing complexity were used to culture biofilms of wound-relevant pathogens, before exposure to test dressings. Confocal microscopy, staining, and imaging of biofilm constituents, total viable counting, and elemental analysis were conducted to assess dressing antibiofilm performance. Live/dead staining and viable counting of biofilms demonstrated that the NGAD was more effective at killing biofilm bacteria than two other standard silver dressings. Staining of biofilm polysaccharides showed that the NGAD was also more effective at reducing this protective biofilm component than standard silver dressings, and image analyses confirmed the superior biofilm killing and removal performance of the NGAD. The biofilm-disruptive and silver-enhancing modes of action of the NGAD were supported by significant differences (p<0.05) in biofilm elemental markers and silver donation. Thisin vitrostudy improves our understanding of how antibiofilm dressing technology can be effective against the challenge of biofilm.

Background: Hard-to-heal wounds are often compromised by the presence of biofilm. This presents an infection risk, yet traditional antimicrobial wound care products and systemic antibiotics are often used despite the uncertainty of therapeutic success and wound progression. The aim of this study was to investigate the clinical impact of a next-generation anti-biofilm Hydrofiber wound dressing (AQUACEL Ag+ Extra[AQAg+ E]) in hard-to-heal wounds that had previously been treated unsuccessfully with traditional silver-, iodine- or polyhexamethylene biguanide (PHMB)-containing dressings and products and/or systemic antibiotics. Methods: Clinical case study evaluations of the anti-biofilm dressing were conducted, where deteriorating or stagnant wounds were selected by clinicians and primary dressings were replaced by the anti-biofilm dressing for up to 4 weeks, or as deemed clinically appropriate, with monitoring via case report forms. The data was stratified for cases where traditional silver-, iodine- or PHMB-containing products, or systemic antibiotics, had been used prior to the introduction of the anti-biofilm dressing. Results: Sixty-five cases were identified for inclusion, wounds ranging in duration from 1 week to 20 years (median: 12 months). In 47 (72%) cases the wounds were stagnant, while 15 (23%) were deteriorating; 3 wounds were not recorded. After an average of 4.2 weeks of management with the anti-biofilm dressing (range: 1–11 weeks), in 11 (17%) cases the wounds had healed (i.e. complete wound closure), 40 (62%) wounds improved, 9 (14%) wounds remained the same and 5 (8%) wounds deteriorated. Conclusions: The introduction of this anti-biofilm dressing into protocols of care that had previously involved wound management with traditional antimicrobial products and/or antibiotics was shown to facilitate improvements in the healing status of most of these hard-to-heal wounds. Dressings containing proven anti-biofilm technology, in combination with antimicrobial silver and exudate management technology, appear to be an effective alternative to traditional antimicrobial products and antibiotics in the cases presented here. The use of antimicrobial wound dressings that contain anti-biofilm technology may have a key role to play in more effective wound management and antibiotic stewardship.

To assess the effectiveness of a new, next-generation antimicrobial dressing (NGAD; AQUACEL Ag+ EXTRA dressing) in managing wound exudate, infection and biofilm, and facilitating progression toward healing. Clinicians from the UK and Ireland selected stalled or deteriorating wounds that were considered to be compromised by infection and/or biofilm. Only the primary dressing was replaced by the NGAD, for up to 4 weeks or as deemed clinically appropriate; otherwise, standard protocols of care were used. Evaluation forms captured the baseline and final assessment characteristics of wound status, exudate levels, skin health, wound bed appearance, signs of infection and biofilm, and wound dimensions. In all, 29 wounds were suitable for inclusion in the final analysis. Following the NGAD evaluation, wound statuses were shifted from stagnant/deteriorating to mainly improved, exudate levels were shifted from moderate/high to moderate/low, and skin health was improved in 20 wounds (69%). Wound bed tissue types were shifted from largely suspected biofilm/sloughy tissue (76%) to largely granulation tissue (53%). All signs of clinical infection were reduced in average frequency, with biofilm suspicion falling from 76% to 45% of the cases. The median management period with the NGAD was 4.5 weeks, after which 26 wounds (90%) became smaller in size and 10 wounds (34%) completely healed. This real-life clinical evaluation of the NGAD suggests that its successful management of exudate, infection and biofilm is generally accompanied by notable improvements in wound health and size, and in some cases, complete healing. The authors are all employed by ConvaTec Ltd. but have no other conflict of interest to declare. Dressings were provided to the clinicians free of charge.