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Microbial sealing: a new approach to reducing contamination
Journal of Hospital Infection (2008) 70(S2) 11–14
Available online at www.sciencedirect.com
www.elsevierhealth.com/journals/jhin
Microbial sealing: a new approach to reducing contamination S.E. Wilson* University of California, Irvine, CA, USA
KEYWORDS Microbial sealant; Surgical site infections; Wound contamination; Skin flora; Skin asepsis
Summary Most surgical site infections (SSIs) are caused by the patient’s endogenous flora, and hence strategies to prevent bacterial contamination of the surgical incision have a central role in the prevention of such infections. However, even with optimal skin preparation, true sterilisation of the skin is not possible. A recently available method of preventing infection is a cyanoacrylate-based microbial sealant (marketed as InteguSeal* Microbial Sealant), which mechanically blocks migration of pathogens to the surgical wound. In in-vitro studies, this preoperative preparation reduced the recovery of pathogens commonly implicated in SSIs by up to 99.9%. Similarly, the incidence of wound contamination was lower with the microbial sealant than with antimicrobial surgical drapes in in-vivo studies. Other studies have shown that this microbial sealant significantly improves the effect of povidone iodine by fixing it on the skin and avoiding wash off, and does not affect normal skin transpiration. In a clinical study in 177 patients, the incidence of wound contamination was 53.0% with the sealant, compared with 68.7% using povidone iodine. The conclusion of this clinical study is that InteguSeal* Microbial Sealant significantly reduces surgical wound bacterial contamination when used in conjunction with 10% povidone iodine skin preparation, as compared to povidone iodine alone. The clinical experience to date is that this sealant is easy to apply and can be used with a variety of skin preparation solutions and with most wound closure techniques. It also has a good safety profile. This preparation may therefore form a valuable part of strategies to reduce bacterial contamination of surgical incisions, thereby potentially decreasing the risk of SSIs. © 2008 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
Introduction The majority of surgical site infections (SSIs) are caused by the patient’s endogenous flora * Samuel E. Wilson MD. UC IRVINE Medical Center, 101 City Drive S., City Tower, Suite 810, Orange, CA 92868, USA. E-mail: [email protected] (S.E. Wilson).
carried on the skin or mucous membranes or in hollow viscera. 1,2 The most commonly implicated pathogens are aerobic Gram-positive cocci such as staphylococci, but Gram-negative organisms and anaerobes may be involved when the operative site is near the groin or perineum. 1 The level of bacterial contamination of the surgical site is an
0195-6701/$ - see front matter © 2008 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
12 important factor determining the risk of SSI. 1 Data from the US National Nosocomial Infections Surveillance (NNIS) system suggest that the incidence of SSIs increases from 2.1% with clean wounds (defined according to the US National Research Council criteria 3 ) to 3.3% with clean-contaminated wounds, 6.4% with contaminated wounds and 7.1% with dirty wounds. 4 Interventions aimed at reducing the risk of bacterial contamination of the surgical incision, for example preoperative washing with antiseptic, preparation of the skin with iodophors or alcohol-based products, and the use of sterile drapes, therefore form a central part of strategies to prevent SSIs. 1 However, even with optimal skin preparation, total sterilisation of the skin is not possible. 5 Recently, a microbial sealant (InteguSeal* Microbial Sealant; Kimberly-Clark Health Care, Roswell, USA) has become available, which is designed to prevent the migration of potential pathogens from the skin into the incision. The preclinical evaluation and initial clinical trial data with this preparation are reviewed in this paper.
Physical properties of InteguSeal* The microbial sealant is a cyanoacrylate-based liquid which polymerises on application to the skin to form a continuous barrier that prevents migration of skin flora into the incision. This preparation also seals microabrasions on the skin, thus preventing recolonisation of such spaces with potential pathogens following skin sterilisation (‘greenhouse’ effects). By contrast, conventional skin-sterilising preparations such as iodophors do not adequately penetrate microabrasions and thus do not prevent recolonisation. Another important factor is that, on account of its mechanical properties, InteguSeal* does not encourage the development of further bacterial resistance.
S.E. Wilson
Figure 1. Impact of microbial sealant (InteguSeal*) on the recovery of common pathogens implicated in SSIs in an invitro surgical incision model.
These in-vitro data are supported by an in-vivo study in pigs, which compared the efficacy of the microbial sealant and an antimicrobial incise drape. A total of 66 4-inch (10.2 cm) incisions with prolonged (60 min) blunt dissection, retraction, and irrigation were made in order to simulate a surgical procedure. In all cases, the skin was prepared with 10% povidone iodine plus either the microbial sealant or an antimicrobial drape, and the wounds were sampled for bacterial contamination immediately after incision and before wound closure. The microbial sealant resulted in six times less wound contamination than with the antimicrobial drape, both after incision and before wound closure, although the difference was statistically significant only before wound closure (Figure 2). In a second study, the incision site was pretreated with S. aureus before skin preparation in order to simulate a level of contamination comparable with that in the human gut. Bacterial wound contamination during the procedure was consistently lower when the microbial sealant was applied following skin preparation with povidone iodine than when povidone iodine was used alone. A further in-vivo study used a scrub and prep technique to investigate the performance of the
The ability of the microbial sealant to immobilise skin flora was initially evaluated in an in-vitro skin incision model. In this system, recovery of meticillin-resistant Staphylococcus aureus (MRSA) was reduced by 99.9% with the sealant, while the recoveries of S. epidermidis and Escherichia coli were reduced by 99.5% and 96.6%, respectively (Figure 1). In a further study with the same model, the microbial sealant reduced by a factor of 101.5 the recovery of drug-resistant Acinetobacter baumannii, another pathogen that has been implicated in SSIs in patients receiving antimicrobial prophylaxis. 6
Mean CFU/incision
Preclinical evaluation 7 6 5 4 3 2 1 0
InteguSeal™ Anti-microbial incise drape
After incision (p = 0.533)
Before closure (p < 0.002)
Figure 2. Wound contamination with microbial sealant (InteguSeal*) or antimicrobial incise drapes in an in-vivo porcine model.
Microbial sealing: a new approach to reducing contamination
13
Fig. 3. Reduction in skin bacteria with microbial sealant (InteguSeal*), alone or in combination with povidone iodine, in an in-vivo cup scrub study.
microbial sealant when used in combination with iodophor or chlorhexidine gluconate (abstract to be presented at ICAAC, Washington, DC, September 2008). The use of microbial sealant, alone or in combination with povidone iodine, resulted in less bacterial skin contamination than povidone iodine alone (Figure 3). Importantly, in an in-vitro study the microbial sealant had no significant effect on water vapour transmission rate, in contrast to either antimicrobial or non-antimicrobial incise drapes (Figure 4). Thus, normal skin transpiration can take place through the sealant film and wound healing process is not affected. The microbial barrier naturally exfoliates with the skin within 2 7 days.
Clinical experience The efficacy of the microbial sealant in preventing wound contamination was compared with standard of care treatment (10% povidone iodine) in a randomised, prospective, multicentre study involving 177 patients undergoing open, clean, inguinal hernia repair. This population was chosen because (contrary to widespread opinion) they are
Total Wound Contamination Rates (at least 1 CFU) 100 %
p=0.04 % of patients with wound contamination
Figure 4. In-vitro water vapour transmission rate with microbial sealant (InteguSeal*) and surgical drapes.
at risk of SSI, and because an SSI in this situation would compromise the aim of the operation, necessitating replacement of the prosthesis and secondary hernia repair. 7 The primary endpoint was the incidence of wound contamination (defined as bacterial counts >0), which occurred in 53.0% of patients with the microbial sealant and 68.7% of patients with povidone iodine (16% difference, P = 0.04). The microbial sealant resulted in decreased bacterial contamination both before and after surgery, and was independent of the use of antimicrobial prophylaxis or preoperative hair removal (Figure 5). In this study, participating surgeons were also asked to rate the ease of use of the microbial sealant on a 0 10 scale (where 10 indicates the greatest difficulty). The surgeons consistently rated the sealant highly with respect to ease of application (mean score ±SD: 0.5 ± 1.1), ability to incise the sealant (0.0 ± 0.2), ability to staple or suture through it (both 0.0 ± 0.0), and visualisation of surgical markers (0.1 ± 0.5). A further advantage
75 %
69% 50 %
53%
25 %
0% Control Group (57 of 83 patients)
InteguSeal* Group (44 of 83 patients)
Figure 5. Incidence of wound contamination with microbial sealant (InteguSeal*) or 10% povidone iodine (controls) in patients undergoing hernia repair, according to surgical variables.
14
S.E. Wilson
identified during the study was that the microbial sealant appeared to improve the adhesion of surgical drapes to the inguinal area.
Conclusions This microbial sealant has been shown to form an effective skin barrier that immobilises bacteria remaining on the skin after conventional preparation, preventing their migration into the incision. It is effective in reducing bacterial contamination of the skin both in-vitro and in-vivo, and the clinical experience to date indicates that it is easy to apply and stays on the skin for up to 5 7 days. It can be used with a variety of skin preparation solutions, and with most wound closure techniques, including sutures, staples, and adhesives. It has a good safety profile; it does not produce local irritation or toxicity, and is not associated with acute systemic toxicity. This preparation may therefore form a valuable part of strategies to reduce bacterial contamination of surgical incisions, thereby potentially decreasing the risk of SSIs. Funding: Research funded by Kimberly-Clark but no funds were received directly by the author. Conflict of Interest statement: Author is a consultant to Kimberly-Clark Health Care.
References 1. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR; Hospital Infection Control Practice Advisory Committee. Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol 1999;20:247 278. 2. Altemeier WA, Culbertson WR, Hummel RP. Surgical sources, considerations of endogenous infections types, and methods of control. Surg Clin North Am 1968;48:227 240. 3. Berard F, Gandon J. Postoperative wound infections: the influence of ultraviolet irradiation of the operating room and of various other factors. Ann Surg 1964; 160(Suppl 1):1 192. 4. Culver DH, Horan TC, Gaynes RP, et al. Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infection Surveillance System. Am J Med 1991;91(Suppl 3B): 152S 157S. 5. Gilliam DL, Nelson CL. Comparison of a one-step iodophor skin preparation versus traditional preparation in total joint surgery. Clin Orthop Rel Res 1990;250:258 260. 6. Goh BK, Alkouder G, Lama TK, Tan CE. Multidrug-resistant Acinetobacter baumannii intra-abdominal abscess. Surg Infect (Larchmt) 2005;6:345 347. 7. Deysine M, Ed. Hernia infections. Pathophysiology, diagnosis, treatment, prevention. New York: Dekker; 2003.
Available online at www.sciencedirect.com
www.elsevierhealth.com/journals/jhin
Microbial sealing: a new approach to reducing contamination S.E. Wilson* University of California, Irvine, CA, USA
KEYWORDS Microbial sealant; Surgical site infections; Wound contamination; Skin flora; Skin asepsis
Summary Most surgical site infections (SSIs) are caused by the patient’s endogenous flora, and hence strategies to prevent bacterial contamination of the surgical incision have a central role in the prevention of such infections. However, even with optimal skin preparation, true sterilisation of the skin is not possible. A recently available method of preventing infection is a cyanoacrylate-based microbial sealant (marketed as InteguSeal* Microbial Sealant), which mechanically blocks migration of pathogens to the surgical wound. In in-vitro studies, this preoperative preparation reduced the recovery of pathogens commonly implicated in SSIs by up to 99.9%. Similarly, the incidence of wound contamination was lower with the microbial sealant than with antimicrobial surgical drapes in in-vivo studies. Other studies have shown that this microbial sealant significantly improves the effect of povidone iodine by fixing it on the skin and avoiding wash off, and does not affect normal skin transpiration. In a clinical study in 177 patients, the incidence of wound contamination was 53.0% with the sealant, compared with 68.7% using povidone iodine. The conclusion of this clinical study is that InteguSeal* Microbial Sealant significantly reduces surgical wound bacterial contamination when used in conjunction with 10% povidone iodine skin preparation, as compared to povidone iodine alone. The clinical experience to date is that this sealant is easy to apply and can be used with a variety of skin preparation solutions and with most wound closure techniques. It also has a good safety profile. This preparation may therefore form a valuable part of strategies to reduce bacterial contamination of surgical incisions, thereby potentially decreasing the risk of SSIs. © 2008 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
Introduction The majority of surgical site infections (SSIs) are caused by the patient’s endogenous flora * Samuel E. Wilson MD. UC IRVINE Medical Center, 101 City Drive S., City Tower, Suite 810, Orange, CA 92868, USA. E-mail: [email protected] (S.E. Wilson).
carried on the skin or mucous membranes or in hollow viscera. 1,2 The most commonly implicated pathogens are aerobic Gram-positive cocci such as staphylococci, but Gram-negative organisms and anaerobes may be involved when the operative site is near the groin or perineum. 1 The level of bacterial contamination of the surgical site is an
0195-6701/$ - see front matter © 2008 The Hospital Infection Society. Published by Elsevier Ltd. All rights reserved.
12 important factor determining the risk of SSI. 1 Data from the US National Nosocomial Infections Surveillance (NNIS) system suggest that the incidence of SSIs increases from 2.1% with clean wounds (defined according to the US National Research Council criteria 3 ) to 3.3% with clean-contaminated wounds, 6.4% with contaminated wounds and 7.1% with dirty wounds. 4 Interventions aimed at reducing the risk of bacterial contamination of the surgical incision, for example preoperative washing with antiseptic, preparation of the skin with iodophors or alcohol-based products, and the use of sterile drapes, therefore form a central part of strategies to prevent SSIs. 1 However, even with optimal skin preparation, total sterilisation of the skin is not possible. 5 Recently, a microbial sealant (InteguSeal* Microbial Sealant; Kimberly-Clark Health Care, Roswell, USA) has become available, which is designed to prevent the migration of potential pathogens from the skin into the incision. The preclinical evaluation and initial clinical trial data with this preparation are reviewed in this paper.
Physical properties of InteguSeal* The microbial sealant is a cyanoacrylate-based liquid which polymerises on application to the skin to form a continuous barrier that prevents migration of skin flora into the incision. This preparation also seals microabrasions on the skin, thus preventing recolonisation of such spaces with potential pathogens following skin sterilisation (‘greenhouse’ effects). By contrast, conventional skin-sterilising preparations such as iodophors do not adequately penetrate microabrasions and thus do not prevent recolonisation. Another important factor is that, on account of its mechanical properties, InteguSeal* does not encourage the development of further bacterial resistance.
S.E. Wilson
Figure 1. Impact of microbial sealant (InteguSeal*) on the recovery of common pathogens implicated in SSIs in an invitro surgical incision model.
These in-vitro data are supported by an in-vivo study in pigs, which compared the efficacy of the microbial sealant and an antimicrobial incise drape. A total of 66 4-inch (10.2 cm) incisions with prolonged (60 min) blunt dissection, retraction, and irrigation were made in order to simulate a surgical procedure. In all cases, the skin was prepared with 10% povidone iodine plus either the microbial sealant or an antimicrobial drape, and the wounds were sampled for bacterial contamination immediately after incision and before wound closure. The microbial sealant resulted in six times less wound contamination than with the antimicrobial drape, both after incision and before wound closure, although the difference was statistically significant only before wound closure (Figure 2). In a second study, the incision site was pretreated with S. aureus before skin preparation in order to simulate a level of contamination comparable with that in the human gut. Bacterial wound contamination during the procedure was consistently lower when the microbial sealant was applied following skin preparation with povidone iodine than when povidone iodine was used alone. A further in-vivo study used a scrub and prep technique to investigate the performance of the
The ability of the microbial sealant to immobilise skin flora was initially evaluated in an in-vitro skin incision model. In this system, recovery of meticillin-resistant Staphylococcus aureus (MRSA) was reduced by 99.9% with the sealant, while the recoveries of S. epidermidis and Escherichia coli were reduced by 99.5% and 96.6%, respectively (Figure 1). In a further study with the same model, the microbial sealant reduced by a factor of 101.5 the recovery of drug-resistant Acinetobacter baumannii, another pathogen that has been implicated in SSIs in patients receiving antimicrobial prophylaxis. 6
Mean CFU/incision
Preclinical evaluation 7 6 5 4 3 2 1 0
InteguSeal™ Anti-microbial incise drape
After incision (p = 0.533)
Before closure (p < 0.002)
Figure 2. Wound contamination with microbial sealant (InteguSeal*) or antimicrobial incise drapes in an in-vivo porcine model.
Microbial sealing: a new approach to reducing contamination
13
Fig. 3. Reduction in skin bacteria with microbial sealant (InteguSeal*), alone or in combination with povidone iodine, in an in-vivo cup scrub study.
microbial sealant when used in combination with iodophor or chlorhexidine gluconate (abstract to be presented at ICAAC, Washington, DC, September 2008). The use of microbial sealant, alone or in combination with povidone iodine, resulted in less bacterial skin contamination than povidone iodine alone (Figure 3). Importantly, in an in-vitro study the microbial sealant had no significant effect on water vapour transmission rate, in contrast to either antimicrobial or non-antimicrobial incise drapes (Figure 4). Thus, normal skin transpiration can take place through the sealant film and wound healing process is not affected. The microbial barrier naturally exfoliates with the skin within 2 7 days.
Clinical experience The efficacy of the microbial sealant in preventing wound contamination was compared with standard of care treatment (10% povidone iodine) in a randomised, prospective, multicentre study involving 177 patients undergoing open, clean, inguinal hernia repair. This population was chosen because (contrary to widespread opinion) they are
Total Wound Contamination Rates (at least 1 CFU) 100 %
p=0.04 % of patients with wound contamination
Figure 4. In-vitro water vapour transmission rate with microbial sealant (InteguSeal*) and surgical drapes.
at risk of SSI, and because an SSI in this situation would compromise the aim of the operation, necessitating replacement of the prosthesis and secondary hernia repair. 7 The primary endpoint was the incidence of wound contamination (defined as bacterial counts >0), which occurred in 53.0% of patients with the microbial sealant and 68.7% of patients with povidone iodine (16% difference, P = 0.04). The microbial sealant resulted in decreased bacterial contamination both before and after surgery, and was independent of the use of antimicrobial prophylaxis or preoperative hair removal (Figure 5). In this study, participating surgeons were also asked to rate the ease of use of the microbial sealant on a 0 10 scale (where 10 indicates the greatest difficulty). The surgeons consistently rated the sealant highly with respect to ease of application (mean score ±SD: 0.5 ± 1.1), ability to incise the sealant (0.0 ± 0.2), ability to staple or suture through it (both 0.0 ± 0.0), and visualisation of surgical markers (0.1 ± 0.5). A further advantage
75 %
69% 50 %
53%
25 %
0% Control Group (57 of 83 patients)
InteguSeal* Group (44 of 83 patients)
Figure 5. Incidence of wound contamination with microbial sealant (InteguSeal*) or 10% povidone iodine (controls) in patients undergoing hernia repair, according to surgical variables.
14
S.E. Wilson
identified during the study was that the microbial sealant appeared to improve the adhesion of surgical drapes to the inguinal area.
Conclusions This microbial sealant has been shown to form an effective skin barrier that immobilises bacteria remaining on the skin after conventional preparation, preventing their migration into the incision. It is effective in reducing bacterial contamination of the skin both in-vitro and in-vivo, and the clinical experience to date indicates that it is easy to apply and stays on the skin for up to 5 7 days. It can be used with a variety of skin preparation solutions, and with most wound closure techniques, including sutures, staples, and adhesives. It has a good safety profile; it does not produce local irritation or toxicity, and is not associated with acute systemic toxicity. This preparation may therefore form a valuable part of strategies to reduce bacterial contamination of surgical incisions, thereby potentially decreasing the risk of SSIs. Funding: Research funded by Kimberly-Clark but no funds were received directly by the author. Conflict of Interest statement: Author is a consultant to Kimberly-Clark Health Care.
References 1. Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR; Hospital Infection Control Practice Advisory Committee. Guideline for prevention of surgical site infection, 1999. Infect Control Hosp Epidemiol 1999;20:247 278. 2. Altemeier WA, Culbertson WR, Hummel RP. Surgical sources, considerations of endogenous infections types, and methods of control. Surg Clin North Am 1968;48:227 240. 3. Berard F, Gandon J. Postoperative wound infections: the influence of ultraviolet irradiation of the operating room and of various other factors. Ann Surg 1964; 160(Suppl 1):1 192. 4. Culver DH, Horan TC, Gaynes RP, et al. Surgical wound infection rates by wound class, operative procedure, and patient risk index. National Nosocomial Infection Surveillance System. Am J Med 1991;91(Suppl 3B): 152S 157S. 5. Gilliam DL, Nelson CL. Comparison of a one-step iodophor skin preparation versus traditional preparation in total joint surgery. Clin Orthop Rel Res 1990;250:258 260. 6. Goh BK, Alkouder G, Lama TK, Tan CE. Multidrug-resistant Acinetobacter baumannii intra-abdominal abscess. Surg Infect (Larchmt) 2005;6:345 347. 7. Deysine M, Ed. Hernia infections. Pathophysiology, diagnosis, treatment, prevention. New York: Dekker; 2003.