Abstract
Abstract
Background:
Despite advances in incision care and surgical dressings, surgical site infections remain a common complication. Post-operative contamination of a surgical site is believed to play a role in many of these infections. Most surgical dressings adhere to the skin with pressure-sensitive adhesives. Cyanoacrylate tissue adhesives bond to skin with much greater strength and have inherent antimicrobial properties. This study was designed to compare the microbial barrier properties of common pressure-sensitive adhesives to medical-grade cyanoacrylate tissue adhesives (2-octyl cyanoacrylate and N-butyl cyanoacrylate).
Methods:
Samples of cyanoacrylate tissue adhesives and pressure-sensitive adhesives were placed on solid culture media. Five common bacterial pathogens were used to contaminate 50 cyanoacrylate samples and 150 pressure-sensitive adhesive samples. Each plate was evaluated for bacterial growth underneath the adhesive sample daily for a total of 72 hours.
Results:
No penetration was seen through any of the cyanoacrylate adhesive samples at 72 hours. In sharp contrast, bacteria penetrated 99.3% of the pressure-sensitive adhesive samples at 72 hours.
Conclusions:
Medical grade cyanoacrylate tissue adhesives provide a superior microbial barrier compared with common pressure-sensitive adhesives. Consideration could be given to the use of these adhesives for the securement of surgical dressings.
Surgical site infections (SSIs) are an unwanted yet relatively common complication after both elective and non-elective surgical procedures. They result in substantial morbidity and contribute to rising healthcare costs. Preventing SSIs has become a primary objective and has led to the development of several formal recommendations for SSI prevention strategies. Until recently, SSI prevention guidelines have focused primarily on risk reduction during the pre-operative and intra-operative periods [1,2]. Recognizing that SSI risk also occurs during the post-operative period has led to more focus on improvements of post-operative incision care and surgical dressings [3].
Surgical dressings have evolved from a more simplistic approach of sterile gauze and tape to more advanced dressings that include gas-permeable polyurethane film (e.g., Tegaderm™ [3M, Minneapolis, MN], Opsite™ [Smith and Nephew, Hull, UK]), hydrocolloids, polyurethane foams, alginates, hydrogels, and contact dressings, commonly made from silicone. These dressings were designed to enhance incision healing and prevent bacterial contamination of incisions. Although some commercially available post-operative dressings are able to prevent penetration of bacteria directly through the product, surgical sites appear to be vulnerable to bacterial challenges at the edge of the dressing [4].
Most surgical dressings are secured to the skin with pressure-sensitive adhesives (PSAs). A wide variety of PSAs have been utilized in medical applications. Categories include acrylics, rubbers, and silicones [5]. The most commonly used PSA on surgical dressing are the acrylic-based PSAs. Although PSAs stabilize the dressing over the site, these dressings remain vulnerable to bacterial contamination. Reasons for vulnerability include: “roll up” of the dressing edge because of poor adherence at points of high sheer force; formation of creases within the dressing because of uneven contour of the skin; bacterial “creep” along the skin surface underneath the poorly adherent edges; and dressings that are constructed with a permeable edge [4,6,7]. Use of an adhesive that allows for stronger adherence at the edges and has the ability to prevent bacterial migration along the skin surface could potentially decrease the risk of post-operative infections.
Cyanoacrylates are a group of strong adhesive polymers. Widely used in industrial applications, various cyanoacrylates have been used in the medical field for years. N-butyl cyanoacrylate and 2-octyl cyanoacrylate are tissue adhesives that have been utilized commonly for incision closure. In vitro studies demonstrate that these adhesives have inherent antimicrobial properties and can provide an effective antimicrobial barrier [8,9]. In addition to primary incision closure, the direct application of cyanoacrylates on top of sutures and staples has been adopted as a means of preventing post-operative infection. Some studies have demonstrated a reduction in SSIs when 2-octyl cyanoacrylate was placed over sternal and spinal incisions after surgery [10–13]. Current SSI prevention guidelines, however, have found insufficient evidence to support or refute the use of such products in this manner [3].
As an alternative to the direct application of cyanoacrylates to a surgical site, this product could also serve as a way of providing secure attachment of a dressing. A dressing utilizing cyanoacrylates for skin adhesion would appear to provide advantage over current PSA dressings when considering adherence and antimicrobial perspectives. However, whether classes of PSAs utilized commonly in healthcare have bacterial barrier properties comparable to the cyanoacrylates is unknown.
Study Objective
To compare the microbial barrier properties of cyanoacrylate adhesives and pressure-sensitive adhesives in an in vitro model.
Methods
In vitro model design
Cyanoacrylate polymers and PSAs were applied in a sterile fashion over a specialized culture media. Five common human bacterial pathogens were placed over the cured adhesives. Detection of organic acids produced by metabolically active bacteria beneath the cured adhesive, within the agar, allowed for visual determination of penetration of bacteria through the adhesive. Each specimen was evaluated at 24-hour intervals over three consecutive days to observe for evidence of growth through the adhesive into the culture media below.
Adhesives
Two U.S. Food and Drug Administration (FDA)-approved cyanoacrylate products were utilized: 2-octyl cyanoacrylate (Dermabond®, Ethicon Inc., Somerville, NJ) and N-butyl-cyanoacrylate (Indermil®, Tyco Healthcare, Norwalk, CT).
Pressure-sensitive adhesives included: Duro-Tak 129A (acrylic polymer-ethyl acetate/vinyl acetate; Henkel Corp., Kansas City, MO); NA33-4110-CC553 (acrylic polymer-vinyl acetate; National Adhesives Corp., Bridgewater, NJ); IPAC–TL7290 (acrylic polymer-vinyl acetate adhesive; Innovative Polymer Adhesive Co., Kansas City, KS); Hollister Medical Adhesive Spray H-7730 (organosilicone-hexamethyldisiloxane; 3M, Maplewood, MN); Nu-Hope Ostomy Adhesive (natural rubber) (Nu-Hope Laboratories, Pacolma, CA); Osto-Bond Adhesive (natural rubber/latex) (Montreal Ostomy, Inc., Vaudreuil-Dorion, Quebec, Canada).
Bacterial preparations
Fresh cultures from the American Type Culture Collection (ATCC) were utilized. Strains included: Staphylococcus epidermidis (ATCC 14990), Staphylococcus aureus (ATCC 29213), methicillin-resistant Staphylococcus aureus (MRSA; ATCC BAA 1026), vancomycin-resistant Enterococcus faecalis (ATCC 51299), and Escherichia coli (ATCC 25922). Bacteria were grown on blood agar at 37°C for 18–24 hours. The bacterial isolate was sampled and placed in normal saline to make a suspension of cells that fell within 0.5–0.6 McFarland turbidity standard (i.e., 1.5–1.8 × 108 organisms per milliliter). Bacterial inoculums were prepared just prior to the experiment to ensure consistent bacterial suspensions.
Microbial cultures
D/E Neutralizing Agar (Becton, Dickinson & Company, Franklin Lakes, NJ) containing the pH-sensitive dye bromocresol purple (5,5′-dibromo-o-cresolsulfonphthalein) was used for all experiments. Production of organic acids by metabolically active bacteria resulted in agar color change from purple to yellow that was detected visually. Lack of media color change would signify the prevention of bacterial penetration through the adhesive.
All tissue adhesives were dispensed from their original packaging. Samples of each cyanoacrylate and PSA were placed on the agar in sterile fashion and incubated for 48 hours to ensure none of the samples were contaminated. Each adhesive was applied to the agar in a uniform, sterile manner to produce a thick film ≥20 mm in diameter and allowed to cure completely. Ten microliters of bacterial dilution was placed on top of the cured adhesive. Five plates were made for each bacteria/adhesive combination. Agar plates contaminated with study bacteria in the absence of tissue adhesive were utilized for positive controls. Test plates were incubated adhesive side up for three days at 37°C. Plates were observed for visible growth and agar color change every 24 hours during the incubation period, with final observation at 72 hours.
Results
Two cyanoacrylates and six PSAs were evaluated in this in vitro model (Table 1). A total of 200 test plates were evaluated. Each type of adhesive was challenged with standard solutions of five common bacterial pathogens (Staphylococcus epidermidis, Staphylococcus aureus, MRSA, Enterococcus faecalis, and Escherichia coli). For each of the five bacteria, five test plates were used per adhesive resulting in 25 test plates for each of the adhesives tested. Each plate was evaluated every 24 hours for a period of three days.
Adhesives
During the 72 hours of observation, there was no evidence of bacterial penetration through any of the 50 cyanoacrylate samples. In sharp contrast, after only 24 hours, bacterial penetrance was noted through 144 of 150 PSA samples. At 72 hours, five additional PSA plates were noted to have bacterial penetrance, resulting in an overall failure rate of 99.3% (Table 2). The one PSA plate that demonstrated prevention of bacterial penetration had been plated with Staphylococcus epidermidis on a natural rubber/latex adhesive. There was no evidence of adhesive contamination on the negative control plates. All positive control plates yielded viable bacteria. All color changes in the media plates were easily identified.
Penetration of Bacteria through Adhesive Samples
Staphylococcus epidermidis.
Discussion
Surgical site infections remain the most common health-care–associated infection, occurring in 2%–5% of those undergoing inpatient surgical procedures in the United States [14]. Recent analysis of U.S. data suggests on average, a post-operative wound infection can add 11.2 days to hospital length of stay and $3–$3.5 billion dollars in hospital-associated costs [15]. Of particular concern are SSIs that occur after prosthetic joint implantation or those involving antimicrobial-resistant organisms. Costs associated with these infections can exceed $90,000 each. With an aging population, the total number of hip and knee arthroplasties and the risk of infection with these procedures is expected to rise substantially over the next 15 years [16,17]. Of particular importance is the morbidity associated with these devastating infections. In 1999 guidelines for prevention of SSIs and in 2004 guidelines for antimicrobial surgical prophylaxis were introduced. Adoption of these guidelines has led to standardized evidence-based interventions that have been shown to reduce post-operative infections [1,2,18,19]. Despite these practice alterations, however, SSIs remain a challenge. Recent evaluations have determined that more than 50% of these infections are preventable and that improved prevention strategies are still needed [20]. Providing effective post-operative incision care strategies is likely to reduce the risk of these costly infections further.
In this study, we compared the antimicrobial barrier properties of two FDA-approved cyanoacrylates to common classes of PSAs utilized to adhere dressings and devices to the skin. We found cyanoacrylate adhesives provided superb bacterial barrier properties, allowing no penetrance through 50 samples tested after 72 hours of contamination. This is in contrast to rapid penetrance of bacteria through PSAs, a class of adhesives that are used commonly to secure surgical dressings to the skin.
In this study, which relied upon visualization of a pH sensitive agar, we were able to differentiate definitively bacterial growth among positive plates. In each sample examined, there was a clear color change from purple to yellow that occurred underneath the adhesive. The remainder of the plate showed no evidence of color change, suggesting that the bacterial growth was directly related to bacterial penetrance through the adhesive. In addition, we included positive and negative control plates that provided further support of the effectiveness of this in vitro model for examining the bacterial barrier properties of these compounds. Similar models have previously been used to demonstrate microbial barrier properties of 2-octyl cyanoacrylate [8,9].
Cyanoacrylates were first introduced in the early 1940s. Upon contact with the skin, cyanoacrylate tissue adhesives quickly undergo polymerization and typically cure within a few minutes, resulting in a strong bond to the skin. Limited use of the tissue adhesive (N-butyl cyanoacrylate) was seen during the Vietnam War. Cyanoacrylate polymers were also used as dental cements and orthodontic bracket adhesives beginning in the 1960s [21]. In 1998, 2-octyl cyanoacrylate (Dermabond) received FDA approval for wound approximation. This was followed by the approval of N-butyl cyanoacrylate (Indermil) in 2001 for similar indications.
Following polymerization, cyanoacrylates adhere tightly to the skin. By-products produced during the polymerization process are believed to have antimicrobial properties [22]. These innate barrier and antimicrobial properties made use of cyanoacrylate tissue adhesives directly over surgical incisions a natural progression. However, a limitation of such practice is that the cyanoacrylate-skin bond is often greatly weakened or completely disrupted by fluids that drain from incisions during the early post-operative period. This disruption of the cyanoacrylate-skin bond eliminates the advantages of the antimicrobial barrier produced by cyanoacrylates that are applied directly over certain surgical incisions. Furthermore, the residual cyanoacrylate can act as a foreign body near the incision edge, further increasing the risk of infection.
When considering that many current dressings are vulnerable to contamination at the dressing edge, future surgical dressing designs that use cyanoacrylate tissue adhesives to secure the perimeter of the dressing to the skin has several advantages. If placed shortly after completion of the surgical procedure, advantages of such a dressing construct may include inhibition of “bacterial creep” underneath the dressing and robust resistance to dressing roll-up, particularly in areas of increased incision tension (e.g., hip or knee incision). In addition, mild post-operative incision drainage would commonly be absorbed by the central aspect of the dressing and be less likely to compromise a peripherally placed cyanoacrylate barrier. The peripherally placed barrier would also be unlikely to serve as a foreign body as it is placed away from the incision edge.
Although earlier studies have suggested that the antimicrobial properties of this compound result from the by-products of polymerization at the time of application and would perhaps have limited influence at later time points, our studies support that the antimicrobial barrier properties remain beyond three days, which is a critical time during which re-epithelialization occurs [23,24].
Given these strong adhesive properties, it is important to note that in order to consider the viability of any dressing adhered to the skin via a cyanoacrylate, a safe removal process will have to be considered.
In conclusion, the results of this study support the hypothesis that cured cyanoacrylate tissue adhesives provide a superior bacterial barrier. Furthermore, PSAs that are utilized commonly to attach dressings to the skin are ineffective in preventing bacterial penetration. Alternative adhesives, such as cyanoacrylates should be considered for such application.
Footnotes
Acknowledgment
This work was supported by the Institute for Advancing Medical Innovation (IAMI)–University of Kansas.
Author Disclosure Statement
No competing financial interests exist.