Korean J healthc assoc Infect Control Prev.  2024 Jun;29(1):3-9. 10.14192/kjicp.2024.29.1.3.

Antiseptics for Preventing Surgical Site Infections

• Lee JS

• KMID: 2556868
• DOI: http://doi.org/10.14192/kjicp.2024.29.1.3

Abstract

Surgical-site infections (SSIs) are the most common healthcare-associated infections in patients undergoing surgery. Surgical site preparation to prevent SSI is aimed at reducing the number of microorganisms introduced into the operative sites. Antiseptics are used to remove transient bacteria and reduce the number of commensal organisms present on the skin. The most commonly used agents are chlorhexidine, povidone-iodine, and alcohol. All of these agents have broad-spectrum activity against various pathogens. Although each agent has its advantages and disadvantages, alcohol-based antiseptic solutions containing chlorhexidine are recommended in the available guidelines. Further well-designed studies are required to identify the best antiseptics for SSI prevention.

Keyword

Surgical wound infection; Chlorhexidine; Povidone-iodine; Alcohols

Reference

1. Cardoso T, Almeida M, Friedman ND, Aragão I, Costa-Pereira A, Sarmento AE, et al. 2014; Classification of healthcare-associated infection: a systematic review 10 years after the first proposal. BMC Med. 12:40. DOI: 10.1186/1741-7015-12-40. PMID: 24597462. PMCID: PMC4016612.

2. Burke JP. 2003; Infection control - a problem for patient safety. N Engl J Med. 348:651–6. DOI: 10.1056/NEJMhpr020557. PMID: 12584377.

3. Horan TC, Culver DH, Gaynes RP, Jarvis WR, Edwards JR, Reid CR. 1993; Nosocomial infections in surgical patients in the United States, January 1986-June 1992. National Nosocomial Infections Surveillance (NNIS) system. Infect Control Hosp Epidemiol. 14:73–80. DOI: 10.1086/646686. PMID: 8440883.

4. de Lissovoy G, Fraeman K, Hutchins V, Murphy D, Song D, Vaughn BB. 2009; Surgical site infection: incidence and impact on hospital utilization and treatment costs. Am J Infect Control. 37:387–97. DOI: 10.1016/j.ajic.2008.12.010. PMID: 19398246.

5. Kirkland KB, Briggs JP, Trivette SL, Wilkinson WE, Sexton DJ. 1999; The impact of surgical-site infections in the 1990s: attributable mortality, excess length of hospitalization, and extra costs. Infect Control Hosp Epidemiol. 20:725–30. DOI: 10.1086/501572. PMID: 10580621.

6. Jenney AW, Harrington GA, Russo PL, Spelman DW. 2001; Cost of surgical site infections following coronary artery bypass surgery. ANZ J Surg. 71:662–4. DOI: 10.1046/j.1445-1433.2001.02225.x. PMID: 11736828.

7. Oh J, Byrd AL, Park M, Kong HH, Segre JA. NISC Comparative Sequencing Program. 2016; Temporal stability of the human skin microbiome. Cell. 165:854–66. DOI: 10.1016/j.cell.2016.04.008. PMID: 27153496. PMCID: PMC4860256.

8. Claesen J. 2018; Topical antiseptics and the skin microbiota. J Invest Dermatol. 138:2106–7. DOI: 10.1016/j.jid.2018.06.001. PMID: 30244719.

9. Privitera GP, Costa AL, Brusaferro S, Chirletti P, Crosasso P, Massimetti G, et al. 2017; Skin antisepsis with chlorhexidine versus iodine for the prevention of surgical site infection: a systematic review and meta-analysis. Am J Infect Control. 45:180–9. DOI: 10.1016/j.ajic.2016.09.017. PMID: 27838164.

10. Williamson DA, Carter GP, Howden BP. 2017; Current and emerging topical antibacterials and antiseptics: agents, action, and resistance patterns. Clin Microbiol Rev. 30:827–60. DOI: 10.1128/CMR.00112-16. PMID: 28592405. PMCID: PMC5475228.

11. McDonnell G, Russell AD. 1999; Antiseptics and disinfectants: activity, action, and resistance. Clin Microbiol Rev. 12:147–79. DOI: 10.1128/CMR.12.1.147. PMID: 9880479. PMCID: PMC88911.

12. Greenstein G, Berman C, Jaffin R. 1986; Chlorhexidine. An adjunct to periodontal therapy. J Periodontol. 57:370–7. DOI: 10.1902/jop.1986.57.6.370. PMID: 3522851.

13. Gomes BP, Vianna ME, Zaia AA, Almeida JF, Souza-Filho FJ, Ferraz CC. 2013; Chlorhexidine in endodontics. Braz Dent J. 24:89–102. DOI: 10.1590/0103-6440201302188. PMID: 23780357.

14. Davies GE, Francis J, Martin AR, Rose FL, Swain G. 1954; 1:6-Di-4'-chlorophenyldiguanidohexane (hibitane). Laboratory investigation of a new antibacterial agent of high potency. Br J Pharmacol Chemother. 9:192–6. DOI: 10.1111/j.1476-5381.1954.tb00840.x. PMID: 13172429. PMCID: PMC1509439.

15. Jenkins S, Addy M, Wade W. 1988; The mechanism of action of chlorhexidine. A study of plaque growth on enamel inserts in vivo. J Clin Periodontol. 15:415–24. DOI: 10.1111/j.1600-051X.1988.tb01595.x. PMID: 3183067.

16. Bobichon H, Bouchet P. 1987; Action of chlorhexidine on budding Candida albicans: scanning and transmission electron microscopic study. Mycopathologia. 100:27–35. DOI: 10.1007/BF00769565. PMID: 3317060.

17. Hiom SJ, Furr JR, Russell AD, Hann AC. 1996; The possible role of yeast cell walls in modifying cellular response to chlorhexidine diacetate. Cytobios. 86:123–35.

18. Best M, Sattar SA, Springthorpe VS, Kennedy ME. 1990; Efficacies of selected disinfectants against Mycobacterium tuberculosis. J Clin Microbiol. 28:2234–9. DOI: 10.1128/jcm.28.10.2234-2239.1990. PMID: 2121783. PMCID: PMC268154.

19. Günther F, Kaiser SJ, Fries T, Frank U, Mutters NT. 2015; Susceptibility of multidrug resistant clinical pathogens to a chlorhexidine formulation. J Prev Med Hyg. 56:E176–9.

20. Russell AD. 1990; Bacterial spores and chemical sporicidal agents. Clin Microbiol Rev. 3:99–119. DOI: 10.1128/CMR.3.2.99. PMID: 2187595. PMCID: PMC358146.

21. Springthorpe VS, Grenier JL, Lloyd-Evans N, Sattar SA. 1986; Chemical disinfection of human rotaviruses: efficacy of commercially-available products in suspension tests. J Hyg (Lond). 97:139–61. DOI: 10.1017/S0022172400064433. PMID: 3016081. PMCID: PMC2082863.

22. Mbithi JN, Springthorpe VS, Sattar SA. 1990; Chemical disinfection of hepatitis A virus on environmental surfaces. Appl Environ Microbiol. 56:3601–4. DOI: 10.1128/aem.56.11.3601-3604.1990. PMID: 2176450. PMCID: PMC185032.

23. Best M, Springthorpe VS, Sattar SA. 1994; Feasibility of a combined carrier test for disinfectants: studies with a mixture of five types of microorganisms. Am J Infect Control. 22:152–62. DOI: 10.1016/0196-6553(94)90004-3. PMID: 7943926.

24. Gélinas P, Goulet J. 1983; Neutralization of the activity of eight disinfectants by organic matter. J Appl Bacteriol. 54:243–7. DOI: 10.1111/j.1365-2672.1983.tb02613.x. PMID: 6687886.

25. Schlett CD, Millar EV, Crawford KB, Cui T, Lanier JB, Tribble DR, et al. 2014; Prevalence of chlorhexidine-resistant methicillin-resistant Staphylococcus aureus following prolonged exposure. Antimicrob Agents Chemother. 58:4404–10. DOI: 10.1128/AAC.02419-14. PMID: 24841265. PMCID: PMC4136006.

26. Jun KI, Choi Y, Kwon K, Shin MJ, Park JS, Song KH, et al. 2019; Chlorhexidine sensitivity in staphylococci isolated from patients with central line-associated bloodstream infection. J Hosp Infect. 103:276–9. DOI: 10.1016/j.jhin.2019.07.009. PMID: 31319094.

27. Wang JT, Sheng WH, Wang JL, Chen D, Chen ML, Chen YC, et al. 2008; Longitudinal analysis of chlorhexidine susceptibilities of nosocomial methicillin-resistant Staphylococcus aureus isolates at a teaching hospital in Taiwan. J Antimicrob Chemother. 62:514–7. DOI: 10.1093/jac/dkn208. PMID: 18477706.

28. Buxser S. 2021; Has resistance to chlorhexidine increased among clinically-relevant bacteria? A systematic review of time course and subpopulation data. PLoS One. 16:e0256336. DOI: 10.1371/journal.pone.0256336. PMID: 34411140. PMCID: PMC8376095.

29. Poole K. 2005; Efflux-mediated antimicrobial resistance. J Antimicrob Chemother. 56:20–51. DOI: 10.1093/jac/dki171. PMID: 15914491.

30. Durani P, Leaper D. 2008; Povidone-iodine: use in hand disinfection, skin preparation and antiseptic irrigation. Int Wound J. 5:376–87. DOI: 10.1111/j.1742-481X.2007.00405.x. PMID: 18593388. PMCID: PMC7951395.

31. Zamora JL. 1986; Chemical and microbiologic characteristics and toxicity of povidone-iodine solutions. Am J Surg. 151:400–6. DOI: 10.1016/0002-9610(86)90477-0. PMID: 3513654.

32. Apostolov K. 1980; The effects of iodine on the biological activities of myxoviruses. J Hyg (Lond). 84:381–8. DOI: 10.1017/S0022172400026905. PMID: 6300223. PMCID: PMC2133914.

33. Kunisada T, Yamada K, Oda S, Hara O. 1997; Investigation on the efficacy of povidone-iodine against antiseptic-resistant species. Dermatology. 195 Suppl 2:14–8. DOI: 10.1159/000246025. PMID: 9403250.

34. Yasuda T, Yoshimura Y, Takada H, Kawaguchi S, Ito M, Yamazaki F, et al. 1997; Comparison of bactericidal effects of commonly used antiseptics against pathogens causing nosocomial infections. Part 2. Dermatology. 195 Suppl 2(Suppl 2):19–28. DOI: 10.1159/000246026. PMID: 9403251.

35. Kawana R, Kitamura T, Nakagomi O, Matsumoto I, Arita M, Yoshihara N, et al. 1997; Inactivation of human viruses by povidone-iodine in comparison with other antiseptics. Dermatology. 195 Suppl 2:29–35. DOI: 10.1159/000246027. PMID: 9403252.

36. Wutzler P, Sauerbrei A, Klöcking R, Brögmann B, Reimer K. 2002; Virucidal activity and cytotoxicity of the liposomal formulation of povidone-iodine. Antiviral Res. 54:89–97. DOI: 10.1016/S0166-3542(01)00213-3. PMID: 12062394.

37. Lepelletier D, Maillard JY, Pozzetto B, Simon A. 2020; Povidone iodine: properties, mechanisms of action, and role in infection control and Staphylococcus aureus decolonization. Antimicrob Agents Chemother. 64:e00682–20. DOI: 10.1128/AAC.00682-20. PMID: 32571829. PMCID: PMC7449185.

38. Tennen R, Setlow B, Davis KL, Loshon CA, Setlow P. 2000; Mechanisms of killing of spores of Bacillus subtilis by iodine, glutaraldehyde and nitrous acid. J Appl Microbiol. 89:330–8. DOI: 10.1046/j.1365-2672.2000.01114.x. PMID: 10971767.

39. Hoekstra MJ, Westgate SJ, Mueller S. 2017; Povidone-iodine ointment demonstrates in vitro efficacy against biofilm formation. Int Wound J. 14:172–9. DOI: 10.1111/iwj.12578. PMID: 26968574. PMCID: PMC7949843.

40. Johani K, Malone M, Jensen SO, Dickson HG, Gosbell IB, Hu H, et al. 2018; Evaluation of short exposure times of antimicrobial wound solutions against microbial biofilms: from in vitro to in vivo. J Antimicrob Chemother. 73:494–502. DOI: 10.1093/jac/dkx391. PMID: 29165561. PMCID: PMC5890786.

41. Bigliardi PL, Alsagoff SAL, El-Kafrawi HY, Pyon JK, Wa CTC, Villa MA. 2017; Povidone iodine in wound healing: a review of current concepts and practices. Int J Surg. 44:260–8. DOI: 10.1016/j.ijsu.2017.06.073. PMID: 28648795.

42. Kiyoyama T, Tokuda Y, Shiiki S, Hachiman T, Shimasaki T, Endo K. 2009; Isopropyl alcohol compared with isopropyl alcohol plus povidone-iodine as skin preparation for prevention of blood culture contamination. J Clin Microbiol. 47:54–8. DOI: 10.1128/JCM.01425-08. PMID: 18971366. PMCID: PMC2620854.

43. Nzekwe IT, Agwuka OI, Okezie MU, Fasheun DO, Nnamani PO, Agubata CO. 2021; Designing an ideal alcohol-based hand sanitizer: in vitro antibacterial responses of ethanol and isopropyl alcohol solutions to changing composition. AAPS Open. 7:5. DOI: 10.1186/s41120-021-00038-x. PMID: 34841045. PMCID: PMC8606244.

44. Gold NA, Mirza TM, Avva U. Hauber S, editor. 2023. Alcohol sanitizer. StatPearls. StatPearls Publishing;Treasure Island (FL):

45. Haft RJ, Keating DH, Schwaegler T, Schwalbach MS, Vinokur J, Tremaine M, et al. 2014; Correcting direct effects of ethanol on translation and transcription machinery confers ethanol tolerance in bacteria. Proc Natl Acad Sci U S A. 111:E2576–85. DOI: 10.1073/pnas.1401853111. PMID: 24927582. PMCID: PMC4078849.

46. Yeung YWS, Ma Y, Liu SY, Pun WH, Chua SL. 2022; Prevalence of alcohol-tolerant and antibiotic-resistant bacterial pathogens on public hand sanitizer dispensers. J Hosp Infect. 127:26–33. DOI: 10.1016/j.jhin.2022.05.017. PMID: 35690267. PMCID: PMC9176178.

47. Omidbakhsh N, Sattar SA. 2006; Broad-spectrum microbicidal activity, toxicologic assessment, and materials compatibility of a new generation of accelerated hydrogen peroxide-based environmental surface disinfectant. Am J Infect Control. 34:251–7. DOI: 10.1016/j.ajic.2005.06.002. PMID: 16765201. PMCID: PMC7132737.

48. Barbut F, Menuet D, Verachten M, Girou E. 2009; Comparison of the efficacy of a hydrogen peroxide dry-mist disinfection system and sodium hypochlorite solution for eradication of Clostridium difficile spores. Infect Control Hosp Epidemiol. 30:507–14. DOI: 10.1086/597232. PMID: 19379098.

49. Painter KL, Strange E, Parkhill J, Bamford KB, Armstrong-James D, Edwards AM. 2015; Staphylococcus aureus adapts to oxidative stress by producing H2O2-resistant small-colony variants via the SOS response. Infect Immun. 83:1830–44. DOI: 10.1128/IAI.03016-14. PMID: 25690100. PMCID: PMC4399076.

50. Baureder M, Reimann R, Hederstedt L. 2012; Contribution of catalase to hydrogen peroxide resistance in Enterococcus faecalis. FEMS Microbiol Lett. 331:160–4. DOI: 10.1111/j.1574-6968.2012.02567.x. PMID: 22486165.

51. Sun D, Crowell SA, Harding CM, De Silva PM, Harrison A, Fernando DM, et al. 2016; KatG and KatE confer Acinetobacter resistance to hydrogen peroxide but sensitize bacteria to killing by phagocytic respiratory burst. Life Sci. 148:31–40. DOI: 10.1016/j.lfs.2016.02.015. PMID: 26860891. PMCID: PMC4792659.

52. World Health Organization (WHO). 2018. Global guidelines for the prevention of surgical site infection. 2nd ed. WHO;Geneva: p. 87–91.

53. Berríos-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, et al. Healthcare Infection Control Practices Advisory Committee. 2017; Centers for disease control and prevention guideline for the prevention of surgical site infection, 2017. JAMA Surg. 152:784–91. DOI: 10.1001/jamasurg.2017.0904. PMID: 28467526.

54. Calderwood MS, Anderson DJ, Bratzler DW, Dellinger EP, Garcia-Houchins S, Maragakis LL, et al. 2023; Strategies to prevent surgical site infections in acute-care hospitals: 2022 update. Infect Control Hosp Epidemiol. 44:695–720. DOI: 10.1017/ice.2023.67. PMID: 37137483. PMCID: PMC10867741.

55. National Institute for Health. 2020. Surgical site infections: prevention and treatment. NICE;London: p. 31.

56. Korea Disease Control. 2017. Guidelines for prevention and control of Healthcare associated infections. KDCA;Chungbuk: p. 263–4.

57. Hadiati DR, Hakimi M, Nurdiati DS, Masuzawa Y, da Silva Lopes K, Ota E. 2020; Skin preparation for preventing infection following caesarean section. Cochrane Database Syst Rev. 6:CD007462. DOI: 10.1002/14651858.CD007462.pub5. PMID: 32580252. PMCID: PMC7386833.

58. Chen S, Chen JW, Guo B, Xu CC. 2020; Preoperative antisepsis with chlorhexidine versus povidone-iodine for the prevention of surgical site infection: a systematic review and meta-analysis. World J Surg. 44:1412–24. DOI: 10.1007/s00268-020-05384-7. PMID: 31996985.

59. Jalalzadeh H, Groenen H, Buis DR, Dreissen YE, Goosen JH, Ijpma FF, et al. 2022; Efficacy of different preoperative skin antiseptics on the incidence of surgical site infections: a systematic review, GRADE assessment, and network meta-analysis. Lancet Microbe. 3:e762–71. DOI: 10.1016/S2666-5247(22)00187-2. PMID: 35985350.

60. National Institute of Health Research Unit on Global Surgery. 2022; Alcoholic chlorhexidine skin preparation or triclosan-coated sutures to reduce surgical site infection: a systematic review and meta-analysis of high-quality randomised controlled trials. Lancet Infect Dis. 22:1242–51. DOI: 10.1016/S1473-3099(22)00133-5. PMID: 35644158.

61. Scott WJ, Eck CD. 2012; Povidone-iodine and ophthalmia neonatorum. Ophthalmology. 119:653–4. author reply 654. DOI: 10.1016/j.ophtha.2011.11.037. PMID: 22385492.

62. David M, Rumelt S, Weintraub Z. 2011; Efficacy comparison between povidone iodine 2.5% and tetracycline 1% in prevention of ophthalmia neonatorum. Ophthalmology. 118:1454–8. DOI: 10.1016/j.ophtha.2010.12.003. PMID: 21439642.

63. Chapman AK, Aucott SW, Milstone AM. 2012; Safety of chlorhexidine gluconate used for skin antisepsis in the preterm infant. J Perinatol. 32:4–9. DOI: 10.1038/jp.2011.148. PMID: 22031047.

64. Barker SJ, Polson JS. 2001; Fire in the operating room: a case report and laboratory study. Anesth Analg. 93:960–5. DOI: 10.1097/00000539-200110000-00031. PMID: 11574364.

65. Hsueh PR, Teng LJ, Yang PC, Pan HL, Ho SW, Luh KT. 1999; Nosocomial pseudoepidemic caused by Bacillus cereus traced to contaminated ethyl alcohol from a liquor factory. J Clin Microbiol. 37:2280–4. DOI: 10.1128/JCM.37.7.2280-2284.1999. PMID: 10364598. PMCID: PMC85137.

66. Vigeant P, Loo VG, Bertrand C, Dixon C, Hollis R, Pfaller MA, et al. 1998; An outbreak of Serratia marcescens infections related to contaminated chlorhexidine. Infect Control Hosp Epidemiol. 19:791–4. DOI: 10.1086/647728. PMID: 9801292.

67. Ko S, An HS, Bang JH, Park SW. 2015; An outbreak of Burkholderia cepacia complex pseudobacteremia associated with intrinsically contaminated commercial 0.5% chlorhexidine solution. Am J Infect Control. 43:266–8. DOI: 10.1016/j.ajic.2014.11.010. PMID: 25557770.

68. Lee S, Han SW, Kim G, Song DY, Lee JC, Kwon KT. 2013; An outbreak of Burkholderia cenocepacia associated with contaminated chlorhexidine solutions prepared in the hospital. Am J Infect Control. 41:e93–6. DOI: 10.1016/j.ajic.2013.01.024. PMID: 23608047.

69. Panlilio AL, Beck-Sague CM, Siegel JD, Anderson RL, Yetts SY, Clark NC, et al. 1992; Infections and pseudoinfections due to povidone-iodine solution contaminated with Pseudomonas cepacia. Clin Infect Dis. 14:1078–83. DOI: 10.1093/clinids/14.5.1078. PMID: 1376156.