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Preliminary analysis of the antimicrobial activity of a novel surgical incise drape containing chlorhexidine gluconate against methicillin-resistant Staphylococcus aureus (MRSA) in an in vivo porcine, incisional-wound model
Address correspondence to Charles E. Edmiston Jr, PhD, Department of Surgery, Medical College of Wisconsin, 8701 Watertown Plank Rd, Milwaukee, WI 53226.
Adhesive plastic surgical drapes are suggested to reduce the risk of wound sepsis.
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Study addresses efficacy of novel chlorhexidine gluconate (CHG)-incised drape in methicillin resistant Staphylococcus aureus porcine wound model.
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CHG surgical drape reduced (P < .001) methicillin resistant S aureus contamination of surgical incision site.
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Compared to iodophor-impregnated drape CHG drape documented greater efficacy.
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Further studies are warranted to assess clinical efficacy of innovative CHG drape.
Background
Surgical site infections occur in at least 2%-4% of all patients. A proposed, risk-reduction strategy has been the use of adhesive, plastic incise drapes to reduce the risk of surgical site infection. The present investigation reports the efficacy of a novel chlorhexidine gluconate (CHG) adhesive surgical drape to reduce the risk of horizontal bacterial migration into surgical wounds, using a porcine model of wound contamination.
Methods
Using a standardized inoculum, and a predetermined randomization schedule, a porcine model was used to assess the efficacy of a CHG-impregnated adhesive drape to prevent MRSA contamination of a simulated surgical wound and intact skin surface compared with an iodophor-impregnated incise drape and a nonantimicrobial incise drape in 0, 1, and 4-hour surgeries.
Results
MRSA recovery from incisional wounds was lowest in sites treated with the CHG drape. The difference was statistically significant (P < .001) at all time points, both between the CHG drape and the nonantimicrobial control as well as between the CHG and iodophor drapes. Mean MRSA recovery from wounds treated with iodophor drapes was slightly lower than nonantimicrobial drapes. The difference was not statistically significant at 0- or 1-hour (P = .065 and P = .089, respectively), however the differences were significant at 4-hours (P = .024).
Discussion
These preliminary results show that a novel CHG surgical incise drape reduced MRSA contamination of a surgical incision site and showed significant antimicrobial activity against contamination of intact skin surfaces compared with an iodophor- impregnated drape.
Conclusions
A novel CHG surgical drape was effective in significantly reducing MRSA contamination in an incisional wound model. Future studies are needed to assess its clinical efficacy.
According to data from the Agency for Healthcare Research and Quality, more than 10 million patients undergo surgical procedures as inpatients each year in the United States, accounting for over one-fourth of all hospital stays.
Surgical site infections (SSIs) occur in at least 2%-4% of all patients undergoing surgical procedures and are a significant cause of patient morbidity/mortality and economic burden to the healthcare system.
In an effort to improve surgical outcomes, evidence-based interventional strategies are consolidated into effective surgical care bundles to mitigate the risk of SSI after all types of surgical procedures.
Do surgical care bundles reduce the risk of surgical site infections in patients undergoing colorectal surgery? A systematic review and cohort meta-analysis of 8,515 patients.
One proposed interventional strategy is the use of adhesive, plastic incise drapes which were introduced over 50 years ago for use in open abdominal procedures.
A common strategy for reducing the microbial burden on the skin prior to surgery involves preadmission antiseptic showers and perioperative skin antisepsis.
Evidence for preadmission showering regimen to achieve maximal antiseptic skin surface concentrations of chlorhexidine gluconate, 4% in surgical patients.
However, recolonization with bacteria, from deeper skin layers and hair follicles, occurs rapidly in the incision during the operation. Adhesive incise drapes have been used to theoretically prevent this, in combination with other draping techniques, by acting as a microbial barrier to prevent bacterial migration and contamination of the wound. The value of this practice is not without controversy, a 2015 Cochrane Collaborative concluded that: “there was no evidence to support the use of plastic, adhesive incise drapes as a method for reducing infection [SSI], and that there was some evidence that infection rates may actually increase when adhesive incise drapes are used.”
Furthermore, updated versions of SSI prevention strategies and CDC guidelines found that: “there is currently no clear difference in the risk of SSI between iodophor-impregnated adhesive drapes compared with no adhesive drapes.”
Chlorhexidine gluconate (CHG) is an alternative antiseptic that can be incorporated into an adhesive incise drape. A Cochrane review concluded that in clean surgeries, preoperative skin preparation with CHG is associated with a lower SSI rate than povidone-iodine.
A 2020 systematic review and network meta-analysis found similar results and concluded that CHG appeared to be twice as effective as povidone iodine in preventing infection after clean surgery.
The Comparative Efficacy of Chlorhexidine Gluconate and Povidone-iodine Antiseptics for the Prevention of Infection in Clean Surgery: A Systematic Review and Network Meta-analysis [e-pub ahead of print].
The present investigation studied the efficacy of a novel adhesive surgical drape impregnated with CHG to reduce the risk of bacterial migration into surgical wounds, using a porcine model of wound contamination.
Material and methods
Test agents
Three different self-adhesive, surgical incise drapes were compared: a novel antimicrobial incise drape containing CHG formulated within the adhesive layer (BeneHold CHG, Avery Dennison, Chicago, IL); an antimicrobial incise drape containing an iodophor formulated within the adhesive layer (3M Ioban 2, 3M Health Care, St. Paul, MN); and a nonantimicrobial incise drape (3M Steri-drape, 3M Health Care, St. Paul, MN).
Experimental animals
A porcine animal model was selected based on its well-established suitability for evaluating antimicrobials for human wound care.
Twelve female domestic swine, aged 6-9 weeks and weighing between 14 and 16 kg, were studied in accordance with the regulations outlined in the US Department of Agriculture Animal Welfare Act (9 CFR, Parts 1, 2, and 3) and the conditions specified in The Guide for Care and Use of Laboratory Animals.
Guide for the Care and Use of Laboratory Animals National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals.
8th ed. National Academies Press (US),
Washington (DC)2011
The animals were housed individually and maintained in a 12-hour light-dark cycle within a room-temperature environment (18°C-26°C, 20%-70% relative humidity), fed once per day, and allowed free ad libitum to water and acclimatized for 7 days.
Experimental protocol
The animals were divided into 3 groups of 4. In 1 group, wounds were left open for 1 hour to simulate short surgery; in another group, to simulated long surgery, the wounds were left open for 4 hours. There was no waiting, open time in the third group, so as to provide initial data as close to time zero as possible. The incision and sampling procedures took approximately 30 minutes.
The skin preparation and incision procedures were the same in all 3 groups. Each animal was anesthetized, and surface hair removed from the entire dorsolateral region to ensure a clean and smooth skin surface. The skin was aseptically prepared using 4% CHG (Hibiclens, Molnlycke Health Care, Norcross, GA) in 70% isopropyl alcohol solution, allowing at least 3 minutes drying time. Eight intended incision sites were designated on the dorsolateral skin surface (Fig 1, 4 on the left and 4 on the right), each site inoculated with 0.1 mL of methicillin resistant Staphylococcus aureus (MRSA) inoculum spread over a 1.0 cm x 3.5 cm area which was allowed to dry for approximately 10 minutes. An adjacent (nonincisional) area was also inoculated in the same manner with the test strain and designated as a control site. Following a predetermined randomization schedule, either a CHG, iodophor, or nonantimicrobial incise drape was applied, covering both inoculated sites. On 1 side, a linear, full thickness incision, approximately 0.5 cm deep and 2.5 cm in length, was made using a #15 scalpel blade, cutting simultaneously through the incise drape and skin. In the incisions designated as 1 hour and 4 hours, retractors were inserted to simulate wound manipulation during surgery.
Fig 1Diagram illustrating the placement of incise drapes over an animal's 8 inoculated incision sites and adjacent skin sites.
At the end of the simulated surgery, the animal was euthanized and tissue samples, weighing between 0.8 and 1.0 g, harvested from each wound that included the incision and approximately 2-3 mm of surrounding skin, together with the incise drape fragment. Another sample of the same size was excised from the inoculated, but nonincisional adjacent site.
Microbiological methods
MRSA (ATCC 33591) inoculum was prepared by washing the cells, re-suspending and diluted with 0.85% sterile saline solution. The final inoculum challenge, 6.6-6.7-log10 colony forming units (cfu)/ml was prepared by serially dilution in 0.85% sterile saline and validated by inoculation to mannitol salt agar plates.
Excised tissue samples were weighed in a sterile Petri dish, homogenized in a sterile tissue grinder and suspended in 5-mL of Dey/Engley (D/E) broth to neutralize the antimicrobial activity of CHG or iodine. Microbial recovery was counted following serial dilution and inoculation to mannitol salt agar plates; surviving cfu were adjusted to yield the number of cfu/gram tissue. The minimal detectable number of surviving MRSA colony forming units was 0.7 log10 cfu/g.
A series of control experiments were conducted to assess the accuracy of the bacterial recovery and counting procedures, including the effectiveness of D/E broth as a neutralizer for both CHG and iodophor.
ASTM International ASTM E1054-08(2013): standard test methods for evaluation of inactivators of antimicrobial agents.
in: A. International, ASTM Pesticides, Antimicrobials, and Alternative Control Agents; Hazardous Substances and Oil Spill Response. American Society for Testing and Materials,
West Conshohocken, PA2020
Neutralizer toxicity was assessed by adding 0.1 mL aliquots of a MRSA suspension (3.7-log10 cfu/ml) to either 5 mL of D/E broth or 5 mL of sterile saline (5 replicates of each) followed by serial dilution and plate-counting. Neutralizer effectiveness was assessed separately for both CHG and iodophor drapes (5 replicates of each) on porcine cadaver skin. Abdominal-ventral swine skin (Tissue Source, Lafayette, IN) was brought to room temperature, cleaned, and allowed to dry. The skin flap was then aseptically prepared using 4% CHG in 70% isopropyl alcohol solution and allowed to air dry for approximately 3 minutes. An antimicrobial drape was applied to the prepared surface, and a 2.5 cm linear incision was made through it using a #15 scalpel. A tissue specimen containing the incision along with a 2-3 mm margin was excised, homogenized, then combined with 5 mL of D/E broth and a 0.1 mL aliquot of the MRSA suspension. Surviving MRSA was quantified by serial dilution and plate-counting. Finally, test product control experiments were performed by inoculating prepared skin flaps with 0.1 mL of the MRSA suspension and allowing it to dry before applying either a CHG or iodophor drape specimen on top (5 replicates of each). After incision, these specimens were left for 4 hours before excising samples, neutralizing the homogenized tissue with D/E broth, and enumerating the surviving MRSA.
Statistical analysis
Statistical analyses were performed using the Minitab software package version 16.2.4 (Minitab Inc, State College, PA). A sample size determination was conducted using data derived from a previous pilot analysis. Assuming a mean difference between treatment groups would be at least 1.4-log10 cfu/g with a standard deviation of 1-log10 cfu/g, a 2-sample t-test with α = 0.05 and β = 0.10, indicated a required sample size of N=10. Data in units of cfu/g were log-transformed before performing statistical analysis. Statistical analyses were performed using the Kaplan-Meier techniques described by Helsel.
The log-rank test was used to evaluate differences between groups, with statistical significance defined as P< .05. The sample means and standard errors derived by Kaplan-Meier analysis were used to compute 95% confidence intervals based on the t-statistic.
Results
The means and ranges of microbial recoveries from incisional wounds and adjacent skin sites treated with nonantimicrobial, CHG, and iodophor drapes collected after 0, 1, and 4-hour surgeries are tabulated in Table 1, together with the number of data points that were below the limit of detection (N < LOD). MRSA recovery from incisional wounds was lowest in sites treated with the CHG drape (Fig 2A). The difference was statistically significant (P < .001) at all time points, both between the CHG drape and the nonantimicrobial control as well as between the CHG and iodophor drapes. Mean MRSA recovery from wounds treated with iodophor drapes was slightly lower than nonantimicrobial drapes. The difference was not statistically significant at 0 or 1-hour (P = .065 and P= .089, respectively); however, the results were significant at 4-hours (P = .024).
Table 1MRSA recovery from wounds and adjacent skin sites treated with non-antimicrobial (“Non-AmX”), CHG, and iodophor drapes in surgeries lasting 0, 1, or 4 hours
Duration [h]
Drape
Mean [log10 cfu/g]
Range [log10 cfu/g]
N
N < LOD
Wound sites
0
Non-AmX
4.0
3.4-4.4
11
0
CHG
1.1
<0.7-2.3
11
8
Iodophor
3.1
<0.8-4.3
10
1
1
Non-AmX
3.8
3.4-4.4
11
0
CHG
1.2
<0.7-2.4
11
6
Iodophor
3.3
<0.7-4.1
10
1
4
Non-AmX
3.7
2.3-4.4
11
0
CHG
1.2
<0.7-2.1
11
6
Iodophor
2.9
<0.7-4.0
10
1
Adjacent skin sites
0
Non-AmX
3.9
3.3-4.2
11
0
CHG
1.4
<0.7-2.4
11
5
Iodophor
2.7
<0.8-3.8
10
1
1
Non-AmX
3.8
3.0-4.4
11
0
CHG
1.1
<0.7-2.4
11
8
Iodophor
2.4
<0.8-4.0
10
3
4
Non-AmX
3.8
2.9-4.3
11
0
CHG
1.0
<0.7-2.6
11
8
Iodophor
1.8
<0.7-3.2
10
4
“N<LOD” denoted the number of data points that were below the limit of detection.
Fig 2Average MRSA recovery from (A) wounds and (B) adjacent skin sites treated with nonantimicrobial (“Non-AmX”), CHG, and iodophor drapes after 0-, 1-, or 4-hour surgeries. Error bars illustrate the 95% confidence intervals. Symbols denote statistically significant differences between Non-AmX and CHG (*), Non-AmX and iodophor (‡), or CHG and iodophor (†).
In the adjacent skin sites, MRSA recovery from under the CHG drapes was the lowest at all time points, and MRSA skin recovery from under the iodophor drapes also decreased in longer surgeries (Fig 2B). Nonantimicrobial drapes were associated with a statistically significantly higher MRSA recovery as compared to both CHG and iodophor at all time points (P ≤ .001). MRSA recovery from under the CHG drapes was statistically significantly lower compared to iodophor drapes at 0- and 1-hour time points (P = .017 and P = .006, respectively), but at 4 hours the difference was not statistically significant (P = .051).
Results from the microbiological method validation study documented that the neutralizer was nontoxic. Recovery of MRSA inoculated into saline and D/E broth averaged 2.7 log10 cfu [range: 2.6-2.7 log10 cfu, 100% recovery] and 2.7 log10 cfu [range: 2.6-2.7 log10 cfu, 97% recovery], respectively. D/E broth was also found to be an effective neutralizer for both CHG and iodophor. MRSA recovery from inoculated D/E broth combined with antimicrobial drape specimens and homogenized porcine skin tissue averaged 2.9 log10 cfu [range: 2.8-2.9 log10 cfu, 104% recovery] for CHG drapes and 2.8 log10 cfu [range: 2.8-2.8 log10 cfu, 103% recovery] for iodophor drapes. Meanwhile, the antimicrobial activity of the 2 drapes after 4 hours of dwell time on inoculated porcine skin resulted in average recoveries of <0.7 log10 cfu (all data points below the limit of detection) for CHG and 1.2 log10 cfu [range: < 0.7-1.9 log10 cfu] for the iodophor drape group.
Discussion
These preliminary results demonstrate that a novel antimicrobial surgical incise drape, containing chlorhexidine gluconate, reduced contamination of a surgical incision site and showed significant antimicrobial activity against MRSA contaminating the skin surface. While both CHG and iodophor drapes documented a decreased MRSA bioburden on intact skin, the CHG drape skin demonstrated a significant reduction of MRSA contamination in the wound bed, whereas the iodophor-based drape was indistinguishable from a nonantimicrobial control. The CHG drape reduced the MRSA burden on intact skin right away, whereas the iodophor drape required 4 hours to reach a similar level of microbial reduction. This rapid antimicrobial activity suggests that fewer skin contaminants could migrate horizontally into the wound following skin incision. A difference in skin adhesiveness may have actually played a role, as well, since a previous study found a correlation between wound contamination and quality of drape adhesiveness, especially at the wound edge.
The results suggest that the novel CHG antimicrobial incise drape may have a significant clinical role in the prevention of SSIs. The benefits of impregnating an antimicrobial agent into an adhesive drape are intuitive, but iodophor-based incise drapes are the only available clinical option and while certain studies have found them to be effective,
Plastic iodophor drape during liver surgery operative use of the iodophor impregnated adhesive drape to prevent wound infection during high risk surgery.
Given that, compared to iodophors, CHG is generally more persistent and better in maintaining efficacy in the presence of blood and organic material, introducing a new CHG-based option might well become an effective component of future SSI prevention bundles.
Furthermore, CHG as a component of a surgical drape based upon previous clinical usage should be view as both effective and safe as reported in a recent WHO report. “Long-term experience with use of chlorhexidine has shown that the incidence of hypersensitivity and skin irritation is low, but severe allergic reactions including anaphylaxis have been reported. Although cytotoxicity has been observed in exposed fibroblasts, no deleterious effects on wound healing have been found in vivo.”
This preliminary analysis had a few noted limitations. First, the study was designed to be an in-vivo assessment of the antimicrobial activity of an innovative CHG drape in an animal porcine model of MRSA skin surface contamination. While the design did include CHG and/or alcohol skin prep, it did not mimic other common preventative techniques such as preoperative CHG bathing. Second, the CHG drape technology was assessed against a single microbial pathogen. While S aureus is a leading microbial pathogen associated with SSI, further analysis is required to validate the broad-spectrum activity of the CHG drape against other bacterial and fungal pathogens. Finally, clinical efficacy can only be assessed through randomized, controlled clinical trials in patients undergoing a wide range of surgical procedures.
Conclusion
A novel surgical drape impregnated with CHG was effective in significantly reducing MRSA contamination in an incisional wound model of contamination when compared with a nonantimicrobial drape or an iodophor impregnated drape. Future studies are needed to assess the clinical efficacy of this novel CHG drape technology in reducing wound contamination. Additional clinical, evidence-based studies are required to determine if a CHG-based antimicrobial drape is effective in reduction of SSI risk, thereby justifying inclusion in an SSI prevention surgical care bundle.
References
Agency for Healthcare Research and Quality
Patient Safety Network (PSNET)
Surgical Site Infection.
2019 (Available at:https://psnet.ahrq.gov/primer/surgical-site-infections. Accessed November 29, 2020)
Do surgical care bundles reduce the risk of surgical site infections in patients undergoing colorectal surgery? A systematic review and cohort meta-analysis of 8,515 patients.
Evidence for preadmission showering regimen to achieve maximal antiseptic skin surface concentrations of chlorhexidine gluconate, 4% in surgical patients.
The Comparative Efficacy of Chlorhexidine Gluconate and Povidone-iodine Antiseptics for the Prevention of Infection in Clean Surgery: A Systematic Review and Network Meta-analysis [e-pub ahead of print].
Guide for the Care and Use of Laboratory Animals National Research Council (US) Committee for the Update of the Guide for the Care and Use of Laboratory Animals.
8th ed. National Academies Press (US),
Washington (DC)2011
ASTM E1054-08(2013): standard test methods for evaluation of inactivators of antimicrobial agents.
(11.08, August 2020)in: A. International, ASTM Pesticides, Antimicrobials, and Alternative Control Agents; Hazardous Substances and Oil Spill Response. American Society for Testing and Materials,
West Conshohocken, PA2020
Plastic iodophor drape during liver surgery operative use of the iodophor impregnated adhesive drape to prevent wound infection during high risk surgery.
WHO Guidelines for Safe Surgery: 2009: Safe Surgery Saves Lives.
World Health Organization,
2009 (Available at:https://www.who.int/patientsafety/safesurgery/tools_resources/9789241598552/en/. Accessed January 22, 2021)
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