Dialkylcarbamoyl chloride (DACC)- coated dressings in the management and prevention of wound infection: a systematic review

Abstract


Background
Wound infections are a significant burden to both the individuals suffering the infected wound and to the healthcare systems treating them.The annual incidence of infected chronic wounds is up to 500,000 cases per year 1 and the incidence of surgical site infections (SSI) is reported as between 5-20% 2 .Apart from the morbidity and social implications of living with a wound infection, the financial costs to the NHS are significant, with the costs of SSI alone estimated at £700 million per annum 3 4 .To date various antimicrobial wound dressings using silver, iodine or Polyhexamethylene biguanide have all been employed to try to reduce the microbial burden within wounds.Dialkylcarbomoylchloride (DACC) coated dressings are a recent addition to this group.
DACC is a fatty acid derivative that is highly hydrophobic.Micro-organisms commonly responsible for causing SSI or colonising chronic wounds generally have hydrophobic extracellular surfaces, and will therefore irreversibly adhere to the DACC coating on dressings 5 .
Subsequent dressing changes will then result in the removal of large numbers of microbes and a decreased bacterial load at the wound site 6 .Mechanical removal of bacteria comes with several additional potential advantages; DACC coated dressings have shown no evidence of wound or systemic absorption of dressing component, or adverse reactions other than to the adhesive component of the dressing 7 .Perhaps most importantly, since the mechanism of antibacterial action is of physical binding and removal, there is no risk of bacteria developing resistance, and the lack of bacteriolysis prevents endotoxin release to the wound bed 8 .Leukomed® Sorbact®, an example of a DACC-coated dressing, is demonstrated in Figure 1.
The aim of this review is to assess the current available evidence supporting the clinical use of DACC coated dressings in managing or preventing wound infections.

Criteria for considering studies for this review
All studies investigating the role of DACC coated dressings in wound care, with primary or secondary outcomes related to infection, were considered for inclusion, including both randomised and non-randomised trials, cohort studies and case series.Only full text reports regarding human subjects and in the English language were included.
Studies were excluded if the report was regarding an in-vitro or basic science study exploring the mode of action of DACC coatings, if DACC was used in conjunction with other advanced dressing systems (such as negative pressure wound therapy), or the article was a case series with less than three cases.

Search Strategy
This systematic review was undertaken in line with recommendations from the PRISMA statement 9 .Medline, Embase, CENTRAL and CINAHL databases were searched from 1946 to September 2016.The full search strategy used is given in table 1.Additional articles were sourced by hand searching the reference lists of relevant articles and via a google scholar search.

Selection of studies and data extraction
Abstracts returned from the above search were assessed for inclusion by three authors acting independently (JT, NB, GS).If felt suitable for inclusion, the full text of the report was obtained and further assessed against inclusion criteria by the same three authors.Any disagreement was resolved by consensus with input from a fourth author (AH).Study design, patient population, sample size, primary and secondary clinical outcomes and results or clinical impressions of the effects of DACC coated dressings were independently extracted by 3 investigators (JT, NB and GS) and collated using a structured data extraction table for analysis.

Assessment of risk of bias in individual studies
The Cochrane risk of bias tool 10 and JADAD scoring system 11 were used to assess methodological quality of randomised controlled trials (RCTs) and cohort studies included in this review.Two reviewers (NB and JT) assessed the risk of bias of included studies independently and collated results in an assessment of risk bias table.
In general, included studies fell into two types; those investigating DACC coated dressings in chronic wounds with or without signs of infection (One RCT 22 , two cohort studies 16 20 and ten case series 12 13 15 17-19 23-26 , total 281 patients) and those investigating the use of DACC coated dressings in the prevention of infection in clean surgical wounds (three RCTs 21 27 28 and one case series 14 , total 3133 patients).

Excluded studies
The full reasons for exclusion are shown in figure 2.

Risk of Bias in included studies
The Cochrane risk of bias tool for RCTs 10 together with JADAD 11 scores demonstrated moderate risk of bias in included studies (tables 3 and 4).The cohort study by Kleintjes 20 was deemed to have a low risk of bias.Of the randomised trials, only the trial by Mosti et al 22 had a JADAD score ≥3.Important sources of bias in the three randomised trials examining DACC for prevention of infection 21 27 28 included a lack of true randomisation, with alternating sequence allocation used in all three trials, and a lack of allocation concealment and assessor blinding in trials.Of the three, only the 2016 study by Stanirowski 27 attempted any form of blinding or concealment, with surgeons 'blinded' to the allocation of the patient until the point of dressing application (at which point they became aware of allocation due to the physical appearance of the test dressings).

DACC coated dressings in chronic wound management
The use of DACC coated dressings in chronically infected wounds was reported in one pilot RCT by Mosti et al 22 , two cohort studies by Kleintjes et al 20 and Gentili et al 16 , and ten case series 12 13 15 17-19 23-26 .
Mosti et al 22 performed a pilot RCT comparing the effects of DACC coated dressings and silver impregnated dressings in chronically infected or heavily colonised leg ulcers of vascular origin.The primary outcome measured was a reduction in bacterial load at day 4 of treatment.They found a reduction of bacterial load of 73.1% in the DACC cohort, compared to a reduction of 41.6% in the silver cohort, a statistically significant reduction (p<0.01).
Although the difference in reduction of bacterial load between the two dressings was statistically significant, there is no comment regarding the clinical significance of this effect.
Kleintjes et al 20 published a cohort study of 13 patients with partial or full-thickness burn wounds, comparing DACC coated dressings with two branded silver impregnated dressings (Acticoat® and Silverlon®).Included wounds were large enough that 2 or 3 dressing types could be applied to different aspects of each wound.Though no statistically significant differences were seen between dressings, authors report that wounds appeared subjectively cleaner, and wound bacterial burden (based on bacterial cultures) was less in swabs from DACC coated dressing sites with 33% positive cultures, compared to the 37.5% in Acticoat and 44% in Silverlon dressing sites.
Gentili et al 16  Investigators reported that 10/15 (66%) had a positive outcome in relation to wound size reduction and that these wounds also demonstrated a reduction in bacterial load measured using real-time PCR.
Ten case series 12 13 15 17-19 23-26 with a total of 209 patients reported mainly subjective results following the use of DACC dressings in chronically infected wounds, with a variety of primary and secondary outcomes including, but not limited to, exudate, erythema, odour, slough and pain.All authors felt that there was significant clinical improvement of the affected wounds (reduction in slough and exudate) seen with DACC coated dressings, but due to the nature of the studies, no quantifiable data could be extracted for synthesis from the studies for the purpose of this review.

DACC coated dressings in the prevention of wound infection in clean surgical wounds
Three RCTs 21 27 28 and one case series 14 examined the use of DACC coated dressings in clean surgical wounds.
Stanirowski et al published both a pilot and a full RCT 27 28 examining post-surgical wound dressing.Patients undergoing caesarean section were randomised to either DACC coated or standard dressings.The pilot study included 142 patients and the full trial 543 patients.
Patients were followed up for 14 days and the presence of SSI was assessed using Centre for Disease Control criteria.In the pilot study the investigators reported a SSI rate of 2.8% in the DACC group compared to 9.8% in the standard dressing group (p = 0.08).This effect size informed the power calculation for the full RCT, which reported overall SSI rates of 1.8% with DACC compared to 5.2% in standard surgical dressings (p=0.04).
Meberg et al 21 recruited 2441 new born infants on an obstetrics ward with the mothers providing consent.Infants were randomised on a 1:1 ratio to either having the umbilical cord stump covered with a DACC coated dressing or daily cleansing with 0.5% chlorhexidine in 70% ethanol solution.Primary outcome was the incidence of new born infection including conjunctivitis, pyoderma, paronychia and omphalitis.Infants were followed up for up to 6 weeks.Overall 377 (15.4%) cases of infection in general were reported.There was no statistical significance in infection rates between the DACC dressing group and the 0.5% chlorhexidine in 70% ethanol solution group (16.3% and 14.6% respectively, p>0.05).
Choi et al 14 presented a case series of seven patients in whom skin grafts were fixed with the use of a DACC-coated wound contact layer and tie-over dressing.All wounds were postexcision of lesion in theatre, and so were clean surgical wounds at the point of application of DACC coated dressings.No wounds experienced infection in this small case series.

Synthesis of results
No meta-analysis of trial data was possible for the included studies, due to differences in trial methodology and outcome measures.There were only two trials 27 28 with similar enough outcome measures and methods to consider a meta-analysis, however the 2014 Stanirowski 28 trial used the observed effect size to influence the power calculation of the 2016 study 27 .It was felt by the authors that a meta-analysis of this data would add nothing further to the findings present in the larger scale RCT.

Discussion
simply alternated between study arms.Primary outcome was reported as SSI according to centre for disease control (CDC) definitions of superficial or deep SSI.However, the follow up period was only 14 days long, which is insufficient to capture all SSI according to the CDC definition which includes wound infection up to 30 days post procedure 29 .Trial methods were improved for the larger study in comparison to the pilot, in that the wound assessments for the larger trial were performed by investigators blinded to dressing type.
This may account for the improvement in the SSI rate in the control group, which was 9.8% in the pilot but reduced to only 5.2% in the full RCT despite identical surgical methods.
This purpose of this review, as outlined above, was to examine the evidence for the clinical use of DACC-coated dressings.Only one article 27 published data on the cost effectiveness of the intervention, which was not taken into consideration in this review.This is due to a significant disparity between the cost of the intervention reported in the article and the actual cost of the intervention on the UK market (mean cost of Leukomed® Sorbact® dressing in the trial reported as €2.80; mean cost of Leukomed® Sorbact® dressings in the UK (as of Aug 2015) £8.06), making any cost analysis difficult to apply to the reviewer's patient cohort.
All of the available evidence does favour DACC coated dressings over conventional, noncoated dressings, and in some cases over more traditional silver coated dressings.This provides further evidence that more research into this field of study would be beneficial.

Limitations of the review
During the search process, at least one article was identified that was classed as a review of the evidence 30 .This was a non-systematic collection of current evidence written on behalf of the product manufacturer that provided a number of references that were included in the search (additional records identified through other sources, figure 2).Our review, in general, agrees with their findings, however the systematic nature of our review, and the stricter inclusion criteria, meant a much smaller number of studies were included.The product literature did include a large amount of unpublished data presented at conferences, that was not included in our review, raising the possibility that the conclusions of our review have been impacted by this data not being made available.
This review did include a large number of low-level studies (small case studies).This was due to a relative paucity of good quality scientific studies into the effects of DACC-coated dressings in comparison to currently accepted standard practice.

Conclusion
DACC coating of dressings shows promise in both the prevention and treatment of wound infections, though published results are not as yet sufficient to firmly conclude either the clinical or cost effectiveness of its use, and therefore directly impact day-to-day clinical practice.However, the available evidence that is presented is in support of DACC coated dressings, and such promise does allow for the undertaking of further high quality research into their clinical and cost effectiveness.

Funding
No external funding was obtained for this review.371

Potential Conflict of interests
examined a novel method of testing bacterial load in the context of a cohort study including 19 patients (20 wounds) with chronically infected vascular ulcers.All patients were treated for four weeks with Cutimed® Sorbact® (DACC coated) dressings changed twice weekly.Panbacterial real-time PCR was used to assess bacterial load at a wound site before and after a four-week treatment course with DACC coated dressings.

Figure 1 .
Figure 1.Photographs of Leukomed® Sorbact®, a commercially available DACC-coated dressing, against a white background.The coloured nature of the wound contact layer is demonstrated.