SURGICAL INFECTIONS Volume 15, Number 4, 2014 ª Mary Ann Liebert, Inc. DOI: 10.1089/sur.2012.193
Impact of Antimicrobial Skin Sealants on Surgical Site Infections Pascal M. Dohmen
Abstract
Background: Surgical site infections (SSIs) after cardiac surgery remains a substantial cause of morbidity and mortality, with increasing costs due to expensive treatment and prolonged hospitalization. Because co-morbidity and bacterial resistance against appropriate antibiotic therapy increases with patient age, new prophylactic innovative strategies are needed. This article provides an overview of the current literature on the impact of microbial skin sealant to prevent SSIs. Methods: A comprehensive review of the literature reporting on microbial skin sealing to prevent surgical site infections was performed. Results: Experimental studies showed that cyanoacrylate microbial sealant decreased skin flora contamination. Additional studies showed that cyanoacrylate not only immobilizes bacteria but also actively prohibits bacterial growth. Randomized clinical studies showed significant quantitative reduction of skin microbes at the surgical site. This results in a decrease of SSIs, which in some studies was statistically significant. Several studies on ‘‘real world’’ patients also showed statistically significant reduction of SSIs. Conclusion: Cyanoacrylate skin sealant can prohibit endogenous bacteria migration and actively reduce bacterial growth, which makes it an attractive option to reduce SSIs.
S
urgical site infection (SSI) is a serious complication in patients undergoing cardiac surgery. The incidence of SSI varies in the literature from 2% to 20%, and it remains a substantial cause of morbidity and mortality [1,2]. Rates of severe deep sternal surgical site infection (i.e., mediastinitis) are reported in the literature; these range from 0.8% to 8.0% [3]. A number of preventive measures have been proposed to reduce the risk of SSI, including skin preparation, effective hand hygiene, antibiotic prophylaxis, operative theater management, asepsis, minimal invasive surgical techniques, and post-operative incision care [4]. Nevertheless, it is impossible to decontaminate completely a patient’s skin, and therefore the risk of wound contamination and subsequent SSI is always present during surgery, even under optimal conditions. Therefore, additional tools or innovative strategies are needed in daily cardiac surgery practice to reduce SSI.
ever, microbial contamination of the surgical site will not necessarily result in a SSI. It is essential to understand the complex ecosystem between the natural endogenous microflora, compresing 1014 microbes, and the host, who contains 1013 mammalian cells [6]. The risk of developing a SSI depends on the ability of the natural host defense mechanism to eliminate these pathogens. Therefore, the amount of inoculated bacteria is important as well as the virulence of the bacterial species. Quantitatively, 105 microorganisms per gram of tissue markedly increase the probability of developing an SSI. If additional prosthetic materials are implanted during a cardiac surgery procedure (for example, a heart valve, conduit, graft material or assist device) only 102 microorganisms per gram of tissue are sufficient to cause infection [6]. Endogenous Flora Contamination of the Surgical Site
Pathogenesis of Surgical Site Infection The patient’s skin, or the endogenous flora therein, is an important source of pathogens prerequisite to developing SSI [5]. During surgery the skin is no longer intact and therefore the natural barrier to resist microbial invasion is lost. How-
For many years, adhesive barrier drapes, with or without antiseptic impregnation, have been used as a strategy to reduce the risk of contamination by endogenous skin flora at the surgical site. The advantage of this option is the reduction of contact between surgical gloves and the patient’s skin; the continuous
Department of Cardiac Surgery, Heart Centre Leipzig, University of Leipzig, Saxony, Germany.
368
ANTIMICROBIAL SKIN SEALANT
369
application of iodine when adhesive drapes with antiseptic impregnation are used reduces the potential for infection of any microorganism that have survived. However, these advantages are not supported by clinical studies so far. The general disadvantage of these adhesive plastic drapes is that they promote bacterial overgrowth through the ‘‘greenhouse effect.’’ A further disadvantage is that some patients have an allergy to iodine, which should be identified preoperatively and excluded. The potential effect of iodine, however, is limited by the inactivated of blood and proteins [7]. From the literature it is not possible to get a clear view of whether adhesive barrier drapes can reduce SSI [8]. The modern anesthesia regime encourages extubation soon after surgery—so called ‘‘fast-track cardiac surgery’’—and this can prevent additional complications. New Pre-Operative Skin Care Strategies One new pre-operative skin care strategy is the use of a cyanoacrylate microbial sealant, which is applied on the top of the commonly used surgical skin preparation. Cyanoacrylate was first synthesized by Airdis in 1949 by combining formaldehyde with alkyl cyanoacetate that after heating depolymerized into a liquid monomer. Kosko [9] evaluated the adhesive properties of cyanoacrylate and the possible application for incised skin closure in upper lid blepharoplasty. However, the breaking strength of cyanoacrylate is only 10–15%, compared with wound closure by using 5-0 monofilament suture material. Therefore, cyanoacrylate derivates can only be used in variety of cosmetic surgical procedures in areas of low tension, such as facial skin and the upper eyelid. Another use for the butyl-cyanoacrylate derivate is preventing intraoperative skin contamination. After initial decontamination with alcohol-based antiseptics, a butylcyanoacrylate-based microbial sealant can be applied to the skin to prevent endogenous bacteria within the hair follicle from migrating into the surgical wound. The sealant polymerizes with the proteins presented in the stratum corneum to form a barrier that immobilizes any bacteria that had survived the application of skin antiseptics. Because of the natural exfoliation of the skin, the microbial sealant gradually wears off after three to seven days. Wilson [10] showed the ability of the microbial sealant to immobilize microbes of the skin flora in an in vitro skin incision model. In this model, there was a significant reduction of wound contamination before skin closure, in using microbial sealant versus an anti-microbial incise drape (p < 0.002). Additionally, this study showed that the use of a microbial sealant had no significant effect on water vapor transmission rate, in contrast with either antimicrobial or non-antimicrobial incise drapes. Bady and Wongworawat [11] introduced Staphylococcus aureus at the incision site to evaluate the effect of antimicrobial drapes versus cyanoacrylate microbial sealant to prevent skin flora contamination of surgical wounds in sheep when compared with a control group. They found that the number of colony-forming units (CFUs) at the iodine-impregnated incisedraped areas (median, 85.5 CFU; range, 6–250 CFU) were similar to the undraped controls (median, 24.5 CFU; range, 0– 212 CFU). However, the microbial sealant showed a highly significant (p > 0.0001) effectiveness barrier in preventing skin flora contamination (median, 0 colony-forming units (CFU); range, 0–2 CFU).
FIG. 1. Superficial and deep incisional surgical site infection reduction was achieved by introducing an antimicrobial sealant after skin disinfection. (2007 vs. 2008, p < 0.018 and 2007 vs. 2008, p < 0.001). Basaran et al. [12] showed that the use of cyanoacrylate not only will immobilize bacteria, but also actively prohibits bacterial growth. This was evaluated in a rat model by performing a sternotomy of 1.5 cm and a suspension of 108 CFU/ mL methicillin-resistant S. aureus (MRSA) was administrated in four groups (n = 40). All incisions were closed and reopened on day three. Except of the sham and control groups, the rats received systemic vancomycin (40 mg/kg/d) intramuscular for 10 d. One group received additional local treatment with butyl-2 cyanoacrylate. The amount of growing microorganisms (CFU/g) was significantly different between the groups receiving vancomycin only or vancomycin and local application of butyl-2 cyanoacrylate (3.83 – 0.58 CFU/g and 2.42 – 0.27 CFU/g, respectively; p < 0.01). The reduction in microbial growth resulted in a better survival in MRSA-infected group because all animals in the control group died, 30% mortality was observed in the vancomycin treated group and only 10% died in the vancomycin in combination with local application of butyl-2 cyanoacrylate group. This study showed not only the active prohibition of microbial growth with cyanoacrylate derivates but also the impressive reduction of mortality in cases of MRSA mediastinitis.
FIG. 2. Mediastinitis was significantly reduced by introducing an antimicrobial sealant after skin disinfection in patients undergoing cardiac surgery. (2007 vs. 2008, p < 0.027 and 2007 vs. 2008, p < 0.006).
370 The first clinical studies were performed by Dohmen et al. [3,13,14], in which the effectiveness of microbial sealant was demonstrated in cardiac surgery patients. A retrospective non-randomized study showed significant reduction of SSI in patients (n = 580) who were skin-sealed compared with the control group (2.3% versus 6.8%, respectively; p = 0.011). Furthermore, because the groups were not randomized, the patients receiving the microbial sealant were at higher risk, identified by the Fowler Combined Operative Risk Score for SSI, as compared with the control group (9.8 – 4.0 versus 8.7 – 3.7, respectively; p < 0.001). Another study, including a larger cohort of 910 prospective patients, supports these data: the microbial sealant reduced SSI in the treated group compared with the untreated group by 1.1% versus 4.6%, respectively (p = 0.025). Both studies are ‘‘real world’’ patient data and not randomized, which limits the impact of these results as it could include some bias. In an additional prospective study involving more than 3,200 patients, there was a significant decrease of SSI (Fig. 1) and mediastinitis (Fig. 2) observed during the past years, which was related to the use of the microbial sealant as no other preventive strategies were changed [15].Von Eckstein et al. [16] enrolled 300 adult patients for elective coronary artery surgery in a randomized multicenter open-label clinical trial (ClinicalTrials.gov NCT00467857). The primary endpoint of this study was the qualitative reduction of the skin microbes at the surgical site from the beginning to the end of the bypass surgery; the results showed a significant change in mean bacterial counts post-incision to post-coronary bypass grafting at the sternal site in the skin sealant group (0.37 log10 CFU/mL), compared with the control group (0.57 log10 CFU/ mL; p = 0.047). At the donor site, a similar significant result was observed (0.09 log10 CFU/mL and 0.27 log10 CFU/mL; p = 0.037). The secondary endpoint of the study only showed a trend towards less SSI in all included patients with skin sealant (9/146 [6.2%]) versus the control group (14/147 [9.5%]; p = 0.285). Interestingly, in a subgroup of patients at high risk for SSI, such as smokers (3/84 [3.6%] versus 11/91 [12.1%]; p = 0.05) or obese patients ([1/40 [2.5%] versus 3/20 [15.0%]; p = 0.015), there was a significant reduction of poststernotomy SSI. This was the first study of a randomized trial on cardiac surgery patients to show a significant reduction of SSI in clinical cases. Waldow et al. [17] initiated a trial of two prospective registries (a microbial skin sealant group (n = 488) versus a control group (n = 495) to evaluate the prophylactic effect of the microbial skin sealant on post-sternotomy mediastinitis (PSM) or superficial SSI. This study could not show a significant influence by the use of a microbial skin sealant to prevent PSM, probably due to the limited number of patients included, although almost 1,000 patients were included. The probability to reduce mediastinitis, however, was indicated by 60% at 3.2% in a control group, which would impact at least 900 patients should be included in each arm of the study. Nevertheless, the authors were able to show a non-statistically significant reduction in the microbial skin group compared with the control group for PSM (2.3% vs. 3.2%, respectively). Iyer et al. [18] performed a randomized, controlled clinical trial of using a microbial sealant treatment at one donor site and untreated at the other donor site of the same patient. This study was terminated after 47 patients were reviewed,
DOHMEN because there was a significant reduction of SSI at the donor site by using the microbial sealant (1/47 [2.1%]), compared with the control group (12/47 [25.5%]; p = 0.001). This trial demonstrated a tremendous reduction of SSI at the donor site; however, the untreated donor site is extremely high and therefore the current preventive strategies should be reviewed. In addition to the studies performed on cardiac surgery patients, there was also a randomized, multi-center clinical trial initiated in elective open inguinal hernia repair to evaluate the impact of a microbial sealant [19] in a total of 177 adult patients selected from six hospitals. The treated group had less wound contamination, compared with the untreated group (31% versus 47%, respectively; p = 0.04). Independent factors to reduce wound contamination were the application of microbial sealant (odds ratio, 0.45; confidence interval, 0.23-0.88; p = 0.02) and perioperative antibiotic use (odds ratio, 0.24; confidence interval, 0.10-0.58; p = 0.001). There are also some limitations of this randomized study because 29 of the 177 patients (16.4%) were lost to follow-up. Additionally, hair removal by shaving was performed in 43%. Several papers have shown in the past that this should be avoided as not only the timing of shaving is critical, but the method of hair removal is also. Summary Although we have a number of pre-operative skin care strategies, such as pre-operative antiseptic showering, hair removal, disinfection of the patient’s skin, adhesive barrier drapes and antimicrobial prophylaxis, to reduce the risk for contamination by endogenous skin flora at the surgical site, using a microbial sealant has additional benefit for patients. There is evidence that the use of microbial sealant is not only a preventive strategy to reduce SSI, but also actively prohibit bacterial growth. Therefore one could also call it an antimicrobial sealant. Conclusion Surgical site infection is a major complication among cardiac surgery patients, so additional preventive strategies are required. It is mandatory to decrease the contamination through endogenous skin flora perioperatively. Therefore, a cyanoacrylate skin sealant can prohibit endogenous bacteria migration and actively reduce bacterial growth. This antimicrobial sealant is an attractive option to reduce SSI. Acknowledgments The author thanks Ms. Anghel for editorial assistance. Author Disclosure Statement No competing financial interests exist. References 1. Brown IWJ, Moor GF, Hummel BW, et al. Toward further reducing wound infections in cardiac operations. Ann Thorac Surg 1996;62:1783–1789. 2. Fry DE. Fifty ways to cause surgical site infections. Surg Infect 2011: 497–500.
ANTIMICROBIAL SKIN SEALANT 3. Borger MA, Rao V, Weisel RD, et al. Deep sternal wound infection: Risk factors and outcomes. Ann Thorac Surg 1998;65:1050–1056. 4. Dohmen PM, Konertz W. A review of current strategies to reduce intraoperative bacterial contamination of surgical wounds. GMS Krankenhaushyg Interdiszip 2007;2:Doc27. 5. Dohmen PM. Influence of skin flora and preventive measures on surgical site infection during cardiac surgery. Surg Infect 2006;7:S13–S17. 6. Tlakalova-Hogenova H, Stepankova R, Hudcovic T, et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett 2004;93:97–108. 7. Magram AJ, Horan TC, Pearson ML, et al. Guidelines for Prevention of Surgical Site Infection, 1999. Center for disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control 1999;27:97–132. 8. Webster J, Alghamdi AA. Use of plastic adhesive drapes during surgery for preventing surgical site infection. Cochrane Database Syst Rev 2007;17:CD006353. 9. Kosko PI. Upper lid blepharoplasty: skin closure achieved with butyl-2-cyanoacrylate. Ophthalmic Surg 1981;12:424– 425. 10. Wilson SE. Microbial sealing: a new approach to reducing contamination. J Hosp Infect 2008;70:S11–14. 11. Bady S, Wongworawat MD. Effectiveness of antimicrobial incise drapes versus cyanoacrylate barrier preparations for surgical sites. Clin Orthop Relat Res 2009;467:1674–1677. 12. Basaran M, Kafali E, Ugurlucan M, et al. Cyanoacrylate gluing increases the effectiveness of systemic antimicrobial treatment in sternal infection: experimental study in a rodent model. Thorac Cardiov Surg 2008;56:28–31. 13. Dohmen PM, Gabbieri D, Weymann A, et al. Reduction in surgical site infection in patients treated with microbial
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15.
16.
17.
18.
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sealant prior to coronary artery bypass graft surgery: a casecontrol study. J Hosp Infect 2009;72:119–126. Dohmen PM, Weymann A, Holinski S, et al. Use of an antimicrobial skin sealant reduces surgical site infection in patients undergoing routine cardiac surgery. Surg Infect 2011;12:475–481. Dohmen PM, Christ T, Linneweber J, Konertz W. The impact of a microbial sealant to reduce surgical site infection in cardiac surgery. Int J Infect Dis 2010;14:suppl 1:E57. von Eckstein AS, Lim CH, Dohmen PM, et al. A randomized trial of a skin sealant to reduce the risk of incision contamination in cardiac surgery. Ann Thorac Surg 2011;92:632–637. Waldow T, Szlapka M, Hensel J, et al. Skin sealant InteguSeal has no impact on prevention of postoperative mediastinitis after cardiac surgery. J Hosp Infect. 2012;81: 278–282. Iyer A, Gilfillan I, Thakur S, Sharma S. Reduction of surgical site infection using a microbial sealant: a randomized trial. J Thorac Cardiovasc Surg 2011;142:438–442. Towfigh S, Cheadle WG, Lowry SF, et al. Significant reduction in incidence of wound contamination by skin flora through use of microbial sealant. Arch Surg 2008;143: 885–891.
Address correspondence to: Prof. Dr. Pascal M. Dohmen Department of Cardiac Surgery Heart Centre Leipzig University of Leipzig Struempellstr. 39, D-04289 Leipzig, Germany E-mail: [email protected]
Impact of Antimicrobial Skin Sealants on Surgical Site Infections Pascal M. Dohmen
Abstract
Background: Surgical site infections (SSIs) after cardiac surgery remains a substantial cause of morbidity and mortality, with increasing costs due to expensive treatment and prolonged hospitalization. Because co-morbidity and bacterial resistance against appropriate antibiotic therapy increases with patient age, new prophylactic innovative strategies are needed. This article provides an overview of the current literature on the impact of microbial skin sealant to prevent SSIs. Methods: A comprehensive review of the literature reporting on microbial skin sealing to prevent surgical site infections was performed. Results: Experimental studies showed that cyanoacrylate microbial sealant decreased skin flora contamination. Additional studies showed that cyanoacrylate not only immobilizes bacteria but also actively prohibits bacterial growth. Randomized clinical studies showed significant quantitative reduction of skin microbes at the surgical site. This results in a decrease of SSIs, which in some studies was statistically significant. Several studies on ‘‘real world’’ patients also showed statistically significant reduction of SSIs. Conclusion: Cyanoacrylate skin sealant can prohibit endogenous bacteria migration and actively reduce bacterial growth, which makes it an attractive option to reduce SSIs.
S
urgical site infection (SSI) is a serious complication in patients undergoing cardiac surgery. The incidence of SSI varies in the literature from 2% to 20%, and it remains a substantial cause of morbidity and mortality [1,2]. Rates of severe deep sternal surgical site infection (i.e., mediastinitis) are reported in the literature; these range from 0.8% to 8.0% [3]. A number of preventive measures have been proposed to reduce the risk of SSI, including skin preparation, effective hand hygiene, antibiotic prophylaxis, operative theater management, asepsis, minimal invasive surgical techniques, and post-operative incision care [4]. Nevertheless, it is impossible to decontaminate completely a patient’s skin, and therefore the risk of wound contamination and subsequent SSI is always present during surgery, even under optimal conditions. Therefore, additional tools or innovative strategies are needed in daily cardiac surgery practice to reduce SSI.
ever, microbial contamination of the surgical site will not necessarily result in a SSI. It is essential to understand the complex ecosystem between the natural endogenous microflora, compresing 1014 microbes, and the host, who contains 1013 mammalian cells [6]. The risk of developing a SSI depends on the ability of the natural host defense mechanism to eliminate these pathogens. Therefore, the amount of inoculated bacteria is important as well as the virulence of the bacterial species. Quantitatively, 105 microorganisms per gram of tissue markedly increase the probability of developing an SSI. If additional prosthetic materials are implanted during a cardiac surgery procedure (for example, a heart valve, conduit, graft material or assist device) only 102 microorganisms per gram of tissue are sufficient to cause infection [6]. Endogenous Flora Contamination of the Surgical Site
Pathogenesis of Surgical Site Infection The patient’s skin, or the endogenous flora therein, is an important source of pathogens prerequisite to developing SSI [5]. During surgery the skin is no longer intact and therefore the natural barrier to resist microbial invasion is lost. How-
For many years, adhesive barrier drapes, with or without antiseptic impregnation, have been used as a strategy to reduce the risk of contamination by endogenous skin flora at the surgical site. The advantage of this option is the reduction of contact between surgical gloves and the patient’s skin; the continuous
Department of Cardiac Surgery, Heart Centre Leipzig, University of Leipzig, Saxony, Germany.
368
ANTIMICROBIAL SKIN SEALANT
369
application of iodine when adhesive drapes with antiseptic impregnation are used reduces the potential for infection of any microorganism that have survived. However, these advantages are not supported by clinical studies so far. The general disadvantage of these adhesive plastic drapes is that they promote bacterial overgrowth through the ‘‘greenhouse effect.’’ A further disadvantage is that some patients have an allergy to iodine, which should be identified preoperatively and excluded. The potential effect of iodine, however, is limited by the inactivated of blood and proteins [7]. From the literature it is not possible to get a clear view of whether adhesive barrier drapes can reduce SSI [8]. The modern anesthesia regime encourages extubation soon after surgery—so called ‘‘fast-track cardiac surgery’’—and this can prevent additional complications. New Pre-Operative Skin Care Strategies One new pre-operative skin care strategy is the use of a cyanoacrylate microbial sealant, which is applied on the top of the commonly used surgical skin preparation. Cyanoacrylate was first synthesized by Airdis in 1949 by combining formaldehyde with alkyl cyanoacetate that after heating depolymerized into a liquid monomer. Kosko [9] evaluated the adhesive properties of cyanoacrylate and the possible application for incised skin closure in upper lid blepharoplasty. However, the breaking strength of cyanoacrylate is only 10–15%, compared with wound closure by using 5-0 monofilament suture material. Therefore, cyanoacrylate derivates can only be used in variety of cosmetic surgical procedures in areas of low tension, such as facial skin and the upper eyelid. Another use for the butyl-cyanoacrylate derivate is preventing intraoperative skin contamination. After initial decontamination with alcohol-based antiseptics, a butylcyanoacrylate-based microbial sealant can be applied to the skin to prevent endogenous bacteria within the hair follicle from migrating into the surgical wound. The sealant polymerizes with the proteins presented in the stratum corneum to form a barrier that immobilizes any bacteria that had survived the application of skin antiseptics. Because of the natural exfoliation of the skin, the microbial sealant gradually wears off after three to seven days. Wilson [10] showed the ability of the microbial sealant to immobilize microbes of the skin flora in an in vitro skin incision model. In this model, there was a significant reduction of wound contamination before skin closure, in using microbial sealant versus an anti-microbial incise drape (p < 0.002). Additionally, this study showed that the use of a microbial sealant had no significant effect on water vapor transmission rate, in contrast with either antimicrobial or non-antimicrobial incise drapes. Bady and Wongworawat [11] introduced Staphylococcus aureus at the incision site to evaluate the effect of antimicrobial drapes versus cyanoacrylate microbial sealant to prevent skin flora contamination of surgical wounds in sheep when compared with a control group. They found that the number of colony-forming units (CFUs) at the iodine-impregnated incisedraped areas (median, 85.5 CFU; range, 6–250 CFU) were similar to the undraped controls (median, 24.5 CFU; range, 0– 212 CFU). However, the microbial sealant showed a highly significant (p > 0.0001) effectiveness barrier in preventing skin flora contamination (median, 0 colony-forming units (CFU); range, 0–2 CFU).
FIG. 1. Superficial and deep incisional surgical site infection reduction was achieved by introducing an antimicrobial sealant after skin disinfection. (2007 vs. 2008, p < 0.018 and 2007 vs. 2008, p < 0.001). Basaran et al. [12] showed that the use of cyanoacrylate not only will immobilize bacteria, but also actively prohibits bacterial growth. This was evaluated in a rat model by performing a sternotomy of 1.5 cm and a suspension of 108 CFU/ mL methicillin-resistant S. aureus (MRSA) was administrated in four groups (n = 40). All incisions were closed and reopened on day three. Except of the sham and control groups, the rats received systemic vancomycin (40 mg/kg/d) intramuscular for 10 d. One group received additional local treatment with butyl-2 cyanoacrylate. The amount of growing microorganisms (CFU/g) was significantly different between the groups receiving vancomycin only or vancomycin and local application of butyl-2 cyanoacrylate (3.83 – 0.58 CFU/g and 2.42 – 0.27 CFU/g, respectively; p < 0.01). The reduction in microbial growth resulted in a better survival in MRSA-infected group because all animals in the control group died, 30% mortality was observed in the vancomycin treated group and only 10% died in the vancomycin in combination with local application of butyl-2 cyanoacrylate group. This study showed not only the active prohibition of microbial growth with cyanoacrylate derivates but also the impressive reduction of mortality in cases of MRSA mediastinitis.
FIG. 2. Mediastinitis was significantly reduced by introducing an antimicrobial sealant after skin disinfection in patients undergoing cardiac surgery. (2007 vs. 2008, p < 0.027 and 2007 vs. 2008, p < 0.006).
370 The first clinical studies were performed by Dohmen et al. [3,13,14], in which the effectiveness of microbial sealant was demonstrated in cardiac surgery patients. A retrospective non-randomized study showed significant reduction of SSI in patients (n = 580) who were skin-sealed compared with the control group (2.3% versus 6.8%, respectively; p = 0.011). Furthermore, because the groups were not randomized, the patients receiving the microbial sealant were at higher risk, identified by the Fowler Combined Operative Risk Score for SSI, as compared with the control group (9.8 – 4.0 versus 8.7 – 3.7, respectively; p < 0.001). Another study, including a larger cohort of 910 prospective patients, supports these data: the microbial sealant reduced SSI in the treated group compared with the untreated group by 1.1% versus 4.6%, respectively (p = 0.025). Both studies are ‘‘real world’’ patient data and not randomized, which limits the impact of these results as it could include some bias. In an additional prospective study involving more than 3,200 patients, there was a significant decrease of SSI (Fig. 1) and mediastinitis (Fig. 2) observed during the past years, which was related to the use of the microbial sealant as no other preventive strategies were changed [15].Von Eckstein et al. [16] enrolled 300 adult patients for elective coronary artery surgery in a randomized multicenter open-label clinical trial (ClinicalTrials.gov NCT00467857). The primary endpoint of this study was the qualitative reduction of the skin microbes at the surgical site from the beginning to the end of the bypass surgery; the results showed a significant change in mean bacterial counts post-incision to post-coronary bypass grafting at the sternal site in the skin sealant group (0.37 log10 CFU/mL), compared with the control group (0.57 log10 CFU/ mL; p = 0.047). At the donor site, a similar significant result was observed (0.09 log10 CFU/mL and 0.27 log10 CFU/mL; p = 0.037). The secondary endpoint of the study only showed a trend towards less SSI in all included patients with skin sealant (9/146 [6.2%]) versus the control group (14/147 [9.5%]; p = 0.285). Interestingly, in a subgroup of patients at high risk for SSI, such as smokers (3/84 [3.6%] versus 11/91 [12.1%]; p = 0.05) or obese patients ([1/40 [2.5%] versus 3/20 [15.0%]; p = 0.015), there was a significant reduction of poststernotomy SSI. This was the first study of a randomized trial on cardiac surgery patients to show a significant reduction of SSI in clinical cases. Waldow et al. [17] initiated a trial of two prospective registries (a microbial skin sealant group (n = 488) versus a control group (n = 495) to evaluate the prophylactic effect of the microbial skin sealant on post-sternotomy mediastinitis (PSM) or superficial SSI. This study could not show a significant influence by the use of a microbial skin sealant to prevent PSM, probably due to the limited number of patients included, although almost 1,000 patients were included. The probability to reduce mediastinitis, however, was indicated by 60% at 3.2% in a control group, which would impact at least 900 patients should be included in each arm of the study. Nevertheless, the authors were able to show a non-statistically significant reduction in the microbial skin group compared with the control group for PSM (2.3% vs. 3.2%, respectively). Iyer et al. [18] performed a randomized, controlled clinical trial of using a microbial sealant treatment at one donor site and untreated at the other donor site of the same patient. This study was terminated after 47 patients were reviewed,
DOHMEN because there was a significant reduction of SSI at the donor site by using the microbial sealant (1/47 [2.1%]), compared with the control group (12/47 [25.5%]; p = 0.001). This trial demonstrated a tremendous reduction of SSI at the donor site; however, the untreated donor site is extremely high and therefore the current preventive strategies should be reviewed. In addition to the studies performed on cardiac surgery patients, there was also a randomized, multi-center clinical trial initiated in elective open inguinal hernia repair to evaluate the impact of a microbial sealant [19] in a total of 177 adult patients selected from six hospitals. The treated group had less wound contamination, compared with the untreated group (31% versus 47%, respectively; p = 0.04). Independent factors to reduce wound contamination were the application of microbial sealant (odds ratio, 0.45; confidence interval, 0.23-0.88; p = 0.02) and perioperative antibiotic use (odds ratio, 0.24; confidence interval, 0.10-0.58; p = 0.001). There are also some limitations of this randomized study because 29 of the 177 patients (16.4%) were lost to follow-up. Additionally, hair removal by shaving was performed in 43%. Several papers have shown in the past that this should be avoided as not only the timing of shaving is critical, but the method of hair removal is also. Summary Although we have a number of pre-operative skin care strategies, such as pre-operative antiseptic showering, hair removal, disinfection of the patient’s skin, adhesive barrier drapes and antimicrobial prophylaxis, to reduce the risk for contamination by endogenous skin flora at the surgical site, using a microbial sealant has additional benefit for patients. There is evidence that the use of microbial sealant is not only a preventive strategy to reduce SSI, but also actively prohibit bacterial growth. Therefore one could also call it an antimicrobial sealant. Conclusion Surgical site infection is a major complication among cardiac surgery patients, so additional preventive strategies are required. It is mandatory to decrease the contamination through endogenous skin flora perioperatively. Therefore, a cyanoacrylate skin sealant can prohibit endogenous bacteria migration and actively reduce bacterial growth. This antimicrobial sealant is an attractive option to reduce SSI. Acknowledgments The author thanks Ms. Anghel for editorial assistance. Author Disclosure Statement No competing financial interests exist. References 1. Brown IWJ, Moor GF, Hummel BW, et al. Toward further reducing wound infections in cardiac operations. Ann Thorac Surg 1996;62:1783–1789. 2. Fry DE. Fifty ways to cause surgical site infections. Surg Infect 2011: 497–500.
ANTIMICROBIAL SKIN SEALANT 3. Borger MA, Rao V, Weisel RD, et al. Deep sternal wound infection: Risk factors and outcomes. Ann Thorac Surg 1998;65:1050–1056. 4. Dohmen PM, Konertz W. A review of current strategies to reduce intraoperative bacterial contamination of surgical wounds. GMS Krankenhaushyg Interdiszip 2007;2:Doc27. 5. Dohmen PM. Influence of skin flora and preventive measures on surgical site infection during cardiac surgery. Surg Infect 2006;7:S13–S17. 6. Tlakalova-Hogenova H, Stepankova R, Hudcovic T, et al. Commensal bacteria (normal microflora), mucosal immunity and chronic inflammatory and autoimmune diseases. Immunol Lett 2004;93:97–108. 7. Magram AJ, Horan TC, Pearson ML, et al. Guidelines for Prevention of Surgical Site Infection, 1999. Center for disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control 1999;27:97–132. 8. Webster J, Alghamdi AA. Use of plastic adhesive drapes during surgery for preventing surgical site infection. Cochrane Database Syst Rev 2007;17:CD006353. 9. Kosko PI. Upper lid blepharoplasty: skin closure achieved with butyl-2-cyanoacrylate. Ophthalmic Surg 1981;12:424– 425. 10. Wilson SE. Microbial sealing: a new approach to reducing contamination. J Hosp Infect 2008;70:S11–14. 11. Bady S, Wongworawat MD. Effectiveness of antimicrobial incise drapes versus cyanoacrylate barrier preparations for surgical sites. Clin Orthop Relat Res 2009;467:1674–1677. 12. Basaran M, Kafali E, Ugurlucan M, et al. Cyanoacrylate gluing increases the effectiveness of systemic antimicrobial treatment in sternal infection: experimental study in a rodent model. Thorac Cardiov Surg 2008;56:28–31. 13. Dohmen PM, Gabbieri D, Weymann A, et al. Reduction in surgical site infection in patients treated with microbial
371
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15.
16.
17.
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sealant prior to coronary artery bypass graft surgery: a casecontrol study. J Hosp Infect 2009;72:119–126. Dohmen PM, Weymann A, Holinski S, et al. Use of an antimicrobial skin sealant reduces surgical site infection in patients undergoing routine cardiac surgery. Surg Infect 2011;12:475–481. Dohmen PM, Christ T, Linneweber J, Konertz W. The impact of a microbial sealant to reduce surgical site infection in cardiac surgery. Int J Infect Dis 2010;14:suppl 1:E57. von Eckstein AS, Lim CH, Dohmen PM, et al. A randomized trial of a skin sealant to reduce the risk of incision contamination in cardiac surgery. Ann Thorac Surg 2011;92:632–637. Waldow T, Szlapka M, Hensel J, et al. Skin sealant InteguSeal has no impact on prevention of postoperative mediastinitis after cardiac surgery. J Hosp Infect. 2012;81: 278–282. Iyer A, Gilfillan I, Thakur S, Sharma S. Reduction of surgical site infection using a microbial sealant: a randomized trial. J Thorac Cardiovasc Surg 2011;142:438–442. Towfigh S, Cheadle WG, Lowry SF, et al. Significant reduction in incidence of wound contamination by skin flora through use of microbial sealant. Arch Surg 2008;143: 885–891.
Address correspondence to: Prof. Dr. Pascal M. Dohmen Department of Cardiac Surgery Heart Centre Leipzig University of Leipzig Struempellstr. 39, D-04289 Leipzig, Germany E-mail: [email protected]
