Principles of Antiseptic Treatments

An antiseptic is defined as an agent able to inhibit the growth and development of microorganisms. These principles can be used on healthy skin, mucous membranes, and cavities or wounds and aim to the complete abolition of local bacterial load. This condition, also if not necessarily associated with an effective infection, has been related to a delay in wound healing or an increased risk of secondary infections. In this context, the main target of different antiseptics is considered to be biofilm. This protected environment inside which bacteria are able to replicate themselves sharing resistance mechanisms represents a bacterial method to maximize the hurtful effect and contemporarily reduce the control chances for host defenses. In the last centuries, huge steps forward have been achieved on the management of antisepsis trying to enhance the effectiveness of different compounds while selecting the substances with the most favorable side effect profiles. This incredibly wide range of possibilities should be adapted to the needs of the single patient to optimize the reliable results while controlling costs. This will allow us to better manage healthcare costs and to reduce patients’ expenditure in terms of quality of life.

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References

  1. Strohal R, Apelqvist J, Dissemond J, et al. The EWMA document: debridement. J Wound Care. 2013;22(1 (Suppl.)):S1–S52. PubMedGoogle Scholar
  2. Nakayama DK. Antisepsis and asepsis and how they shaped modern surgery. Am Surg. 2018;84:766–71. PubMedGoogle Scholar
  3. Rutala WA, Weber DJ, Healthcare Infection Control Practices Advisory Committee (HICPAC). In guideline for disinfection and sterilization in healthcare facilities. Atlanta, GA: CDC; 2008. Google Scholar
  4. Cruse PJE. History of surgical infection. In: Fry DE, editor. Surgical infections. Boston: Little, Brown; 1994. p. 3–10. Google Scholar
  5. Torriani F, Taplitz R. History of infection prevention and control. Infect Dis. 2010:76–85. Google Scholar
  6. Smith PW, Watkins K, Hewlett A. Infection control through the ages. Am J Infect Control. 2012;40(1):35–42. PubMedGoogle Scholar
  7. Furley D, Wilkie J. Galen on respiration and the arteries. In: Princeton University Press, Bylebyl J, editors. 1979, William Harvey and his age. Baltimore: Johns Hopkins University Press; 1984. Google Scholar
  8. Aggarwal BB, Sundaram C, Malani N, Ichikawa H. Curcumin: the Indian solid gold. Adv Exp Med Biol. 2007;595:1–75. PubMedGoogle Scholar
  9. Hsiao CY, Hung CY, Tsai TH, Chak KF. A study of the wound healing mechanism of a traditional Chinese medicine, Angelica sinensis, using a proteomic approach. Evid Based Complement Alternat Med. 2012;2012:467531. PubMedPubMed CentralGoogle Scholar
  10. Gottfried RS. Plague, public health and medicine in late medieval England. In: Bulst N, Delort R, editors. Maladies et société. XII ed. Paris: Editions du CNRS; 1989. p. 337–65. Google Scholar
  11. Miller PJ. Semmelweis. Infect Control. 1982;3:405–9. CASPubMedGoogle Scholar
  12. Best M, Neuhauser D. Ignaz Semmelweis and the birth of infection control. Qual Saf Health Care. 2004;13:233–4. CASPubMedPubMed CentralGoogle Scholar
  13. Krasner RI. Pasteur: high priest of microbiology. ASM News. 1995;61:575–9. Google Scholar
  14. Kaufmann SH. Robert Koch, the Nobel Prize, and the ongoing threat of tuberculosis. N Engl J Med. 2005;353:2423–6. CASPubMedGoogle Scholar
  15. Pitt D, Aubin J-M. Joseph lister: father of modern surgery. Can J Surg. 2012;55:E8–9. PubMedPubMed CentralGoogle Scholar
  16. Boyce JM. Best products for skin antisepsis. Am J Infect Control. 2019;47:17–22. Google Scholar
  17. Williamson DA, Carter GP, Howden BP. Current and emerging topical antibacterials and antiseptics: agents, action, and resistance patterns. Clin Microbiol Rev. 2017;30:827–60. CASPubMedPubMed CentralGoogle Scholar
  18. McDonnell G, Russell AD. Antiseptics and disinfectants: activity, action, and resistance. Clin Microbiol Rev. 1999;12(1):147–79. CASPubMedPubMed CentralGoogle Scholar
  19. McDonnell GE. Antisepsis, disinfection, and sterilization: types, action, and resistance. Washington, DC: ASM Press; 2007. Google Scholar
  20. McCoy WF, Bryers JD, Robbins J, Costerton JW. Observations of fouling biofilm formation. Can J Microbiol. 1981;27:910–7. CASPubMedGoogle Scholar
  21. Kaehn K. Polihexanide: a safe and highly effective biocide. Skin Pharmacol Physiol. 2010;23(suppl 1):7–16. CASPubMedGoogle Scholar
  22. Robson M. Infection in the surgical patient: an imbalance in the normal equilibrium. Clin Plast Surg. 1979;6:493–503. CASPubMedGoogle Scholar
  23. Heinzelmann M, Scott M, Lam T. Factors predisposing to bacterial invasion and infection. Am J Surg. 2002;183:179–90. PubMedGoogle Scholar
  24. Kujath P, Michelsen A. Wounds—from physiology to wound dressing. Dtsch Arztebl Int. 2008;105:239–48. PubMedPubMed CentralGoogle Scholar
  25. Leaper D. Topical antiseptics in wound care: time for reflection. Int Wound J. 2011;8:547–9. PubMedPubMed CentralGoogle Scholar
  26. Claesen J. Topical antiseptics and the skin microbiota. J Investig Dermatol. 2018;138:2106–7. CASPubMedGoogle Scholar
  27. Sotto A, Richard JL, Combescure C, et al. Beneficial effects of implementing guidelines on microbiology and costs of infected diabetic foot ulcers. Diabetologia. 2010;53:2249–55. CASPubMedGoogle Scholar
  28. Watnick P, Kolter R. Biofilm, city of microbes. J Bacteriol. 2000;182(10):2675–9. CASPubMedPubMed CentralGoogle Scholar
  29. Burmolle M, Thomsen TR, Fazli M, et al. Biofilms in chronic infections—a matter of opportunity—monospecies biofilms in multispecies infections. FEMS Immunol Med Microbiol. 2010;59:324–36. PubMedGoogle Scholar
  30. Junka A, Bartoszewicz M, Smutnicka D, Secewicz A, Szymczyk P. Efficacy of antiseptics containing povidone-iodine, Octenidine dihydrochloride and ethacridine lactate against biofilm formed by Pseudomonas aeruginosa and Staphylococcus aureus measured with the novel biofilm-oriented antiseptics test. Int Wound J. 2014;11:730–4. PubMedGoogle Scholar
  31. Bowler PG, Duerden BI, Armstrong DG. Wound microbiology and associated approaches to wound management. Clin Microbiol Rev. 2001;14:244–69. CASPubMedPubMed CentralGoogle Scholar
  32. Marzenna B, Anna R, Marek K, Anna P. Penetration of a selected antibiotic and antiseptic into a biofilm formed on orthopedic steel implants. Orthop Traumatol Rehabil. 2007;9:310–8. Google Scholar
  33. White RJ, Cutting KF. Critical colonization—the concept under scrutiny. Ostomy Wound Manage. 2006;52(11):50–6. PubMedGoogle Scholar
  34. Kingsley A. A proactive approach to wound infection. Nurs Stand. 2001;15(30):50–8. CASPubMedGoogle Scholar
  35. Dissemond J, Assadian O, Gerber V, et al. Classification of wounds at risk and their antimicrobial treatment with polihexanide: a practice-oriented expert recommendation. Skin Pharmacol Physiol. 2011;24:245–55. CASPubMedGoogle Scholar
  36. Brown TS, Hawksworth JS, Sheppard FR, et al. Effect of a new silver dressings on chronic venous leg ulcers. Surg Infect. 2011;12:351–7. Google Scholar
  37. Gabriel GJ, Som A, Madkour AE, Eren T, Tew GN. Infectious disease: connecting innate immunity to biocidal polymers. Mater Sci Eng R Rep. 2007;57:28–64. PubMedPubMed CentralGoogle Scholar
  38. Bath MF, Davies J, Suresh R, Machesney MR. Surgical site infections: a scoping review on current intraoperative prevention measures. Ann R Coll Surg Engl. 2022;104(8):571–6. CASPubMedPubMed CentralGoogle Scholar
  39. Schweizer HP. Triclosan: a widely used biocide and its link to antibiotics. FEMS Microbiol Lett. 2001;202:1–7. CASPubMedGoogle Scholar
  40. Magee P. Antiseptic drugs and disinfectants. In: Aronson JK, editor. Side effects of drugs annual. Amsterdam, The Netherlands: Elsevier; 2010.; Chapter 24; Volume 32. p. 437–43. Google Scholar
  41. Karpinski T, Sopata M, Mankowski B. The antimicrobial effectiveness of antiseptics as a challenge in hard to heal wounds. Leczenie Ran. 2020;17:88–94. Google Scholar
  42. Enzler MJ, Berbari E, Osmon DR. Antimicrobial prophylaxis in adults. Mayo Clin Proc. 2011;86:686–701. CASPubMedPubMed CentralGoogle Scholar
  43. Gottrup F, Apelqvist J, Price P. Outcomes in controlled and comparative studies on non-healing wounds: recommendations to improve the quality of evidence in wound management. J Wound Care. 2010;19:239–68. Google Scholar
  44. Alvarez-Marin R, Aires-de-Sousa M, Nordmann P, Kieffer N, Poirel L. Antimicrobial activity of octenidine against multidrug-resistant gram-negative pathogens. Eur J Clin Microbiol Infect Dis. 2017;36:2379–83. CASPubMedGoogle Scholar
  45. Bond CJ. Remarks on the application of strong antiseptics to infected and non-infected wounds. Br Med J. 1915;1(2827):405–6. CASPubMedPubMed CentralGoogle Scholar
  46. Maillard JY. Antimicrobial biocides in the healthcare environment: efficacy, usage, policies, and perceived problems. Ther Clin Risk Manag. 2005;1:307–20. PubMedPubMed CentralGoogle Scholar
  47. Levy SB. Active efflux, a common mechanism for biocide and antibiotic resistance. Symp Ser Soc Appl Microbiol. 2002;31(Suppl):65S–71S. CASGoogle Scholar
  48. Punjataewakupt A, Napavichayanun S, Aramwit P. The downside of antimicrobial agents for wound healing. Eur J Clin Microbiol Infect Dis. 2019;38(1):39–54. PubMedGoogle Scholar
  49. Fazli M, Bjarnsholt T, Kirketerp-Moller K, et al. Quantitative analysis of the cellular inflammatory response against biofilm bacteria in chronic wounds. Wound Repair Regen. 2011;19:387–91. PubMedGoogle Scholar
  50. Kirketerp-Møller K, Madsen K, Jensen P, et al. The distribution, organization and ecology of bacteria in chronic wounds. J Clin Microbiol. 2008;46:2717–22. PubMedPubMed CentralGoogle Scholar
  51. Pagès JM, Maillard JY, Davin-Regli A, Springthorpe S. Microbicides—the double-edged sword: environmental toxicity and emerging resistance. In: Fraise AP, Maillard J-Y, Sattar A, editors. Russell, Hugo and Ayliffe’s principles and practice of disinfection, preservation and sterilization. 5th ed. Wiley-Blackwell; 2013. Google Scholar
  52. Nunan R, Harding KG, Martin P. Clinical challenges of chronic wounds: searching for an optimal animal model to recapitulate their complexity. Dis Model Mech. 2014;7(11):1205–13. CASPubMedPubMed CentralGoogle Scholar
  53. Lee DH, Vielemeyer O. Analysis of overall level of evidence behind Infectious Diseases Society of America practice guidelines. Arch Intern Med. 2011;171:18–22. PubMedGoogle Scholar
  54. Lipsky BA, Hoey C. Topical antimicrobial therapy for treating chronic wounds. Clin Infect Dis. 2009;49:1541–9. PubMedGoogle Scholar
  55. Warren SJ. The use of topical antimicrobials and antibiotics in wound care. Adv Wound Care. 2011;2:219–24. Google Scholar
  56. Scalise A, Falcone M, Avruscio G, Brocco E, Ciacco E, Parodi A, Tasinato R, Ricci E. What COVID-19 taught us: new opportunities and pathways from telemedicine and novel antiseptics in wound healing. Int Wound J. 2022;19(5):987–95. PubMedGoogle Scholar
  57. Aisa J, Parlier M. Local wound management: a review of modern techniques and products. Vet Dermatol. 2022;33(5):463–78. PubMedGoogle Scholar
  58. Venter H, Henningsen ML, Begg SL. Antimicrobial resistance in healthcare, agriculture and the environment: the biochemistry behind the headlines. Venter H, editor. Essays Biochem. 2017;61(1):1–10. PubMedPubMed CentralGoogle Scholar
  59. Poole K. Efflux-mediated antimicrobial resistance. J Antimicrob Chemother. 2005;56(1):20–51. CASPubMedGoogle Scholar
  60. Alves PJ, Barreto RT, Barrois BM, Gryson LG, Meaume S, Monstrey SJ. Update on the role of antiseptics in the management of chronic wounds with critical colonisation and/or biofilm. Int Wound J. 2021;18(3):342–58. PubMedGoogle Scholar
  61. Zinn J, Jenkins JB, Swofford V, Harrelson B, McCarter S. Intraoperative patient skin prep agents: is there a difference? AORN J. 2010;92:662–74. PubMedGoogle Scholar
  62. de Lissovoy G, Fraeman K, Hutchins V, et al. Surgical site infection: incidence and impact on hospital utilization and treatment costs. Am J Infect Control. 2009;37:387–97. PubMedGoogle Scholar
  63. Berríos-Torres SI, Umscheid CA, Bratzler DW, Leas B, Stone EC, Kelz RR, Reinke CE, Morgan S, Solomkin JS, Mazuski JE, et al. Centers for Disease Control and Prevention Guideline for the Prevention of Surgical Site Infection, 2017. JAMA Surg. 2017;152:784–91. PubMedGoogle Scholar
  64. Mangram A, Horan T, Pearson M, Silver L, Jarvis W. Guideline for prevention of surgical site infection, 1999. Hospital Infection Control Practices Advisory Committee. Infect Control Hosp Epidemiol. 1999;20(4):250–78. CASPubMedGoogle Scholar
  65. Dumville JC, McFarlane E, Edwards P, Lipp A, Holmes A, Liu Z. Preoperative skin antiseptics for preventing surgical wound infections after clean surgery. Cochrane Database Syst Rev. 2015;(4):CD003949. https://doi.org/10.1002/14651858.CD003949.pub4.
  66. Edmonds M, Foster A. The use of antibiotics in the diabetic foot. Am J Surg. 2004;187(5A (Suppl.)):25S–8S. CASPubMedGoogle Scholar
  67. Diana M, Hubner M, Eisenring MC, et al. Measures to prevent surgical site infections: what surgeons (should) do. World J Surg. 2011;35:280–8. PubMedGoogle Scholar
  68. Perencevich EN, Sands KE, Cosgrove SE, et al. Health and economic impact of surgical site infections diagnosed after hospital discharge. Emerg Infect Dis. 2003;9:196–203. PubMedPubMed CentralGoogle Scholar
  69. Zöllner H, Kramer A, Youssef P, Youssef U, Adrian V. Preliminary investigations on the biodegradability of selected microbicidal agents. Hyg Med. 1995;20:401–7. Google Scholar
  70. Freise J, Kohaus S, Korber A, Hillen U, Kroger K, Grabbe S, Dissemond J. Contact sensitization in patients with chronic wounds: results of a prospective investigation. J Eur Acad Dermatol Venereol. 2008;22:1203–7. CASPubMedGoogle Scholar
  71. Edmonds M. Facts that every vascular surgeon needs to know about the diabetic foot. J Cardiovasc Surg. 2014;55(2 Suppl 1):255–63. CASGoogle Scholar
  72. Langer S, Sedigh Salakdeh M, Goertz O, Steinau HU, Steinstraesser L, Homann HH. The impact of topical antiseptics on skin microcirculation. Eur J Med Res. 2004;9:449–54. CASPubMedGoogle Scholar
  73. Müller G, Kramer A. Biocompatibility index of antiseptic agents by parallel assessment of antimicrobial activity and cellular cytotoxicity. J Antimicrob Chemother. 2008;61:1281–7. PubMedGoogle Scholar
  74. Health Quality Ontario. Management of chronic pressure ulcers: an evidence-based analysis. Ont Health Technol Assess Ser. 2009;9(3):1–203. Google Scholar
  75. Game FL, Hinchliffe RJ, Apelqvist J, et al. A systematic review of interventions to enhance the healing of chronic ulcers of the foot in diabetes. Diabetes Metab Res Rev. 2012;28(Suppl. 1):119–41. PubMedGoogle Scholar
  76. Chen W, Xu K, Zhang H, et al. A comparative study on effect of bacterial load in diabetic foot ulcers dealing with iodophor and rivanol respectively [in Chinese]. Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2008;22:567–70. CASPubMedGoogle Scholar
  77. Zelver N, Hamilton M, Pitts B, et al. Measuring antimicrobial effects on biofilm bacteria: from laboratory to field. Methods Enzymol. 1999;310:608–28. CASPubMedGoogle Scholar
  78. Rayman, et al. Guidelines on use of interventions to enhance healing of chronic foot ulcers in diabetes. Diab Metab Res Rev. 2020:e3283. Google Scholar
  79. Ceri H, Olson ME, Stremick C, et al. The Calgary biofilm device: new technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. J Clin Microbiol. 1999;37:1771–6. CASPubMedPubMed CentralGoogle Scholar
  80. Anderl JN, Franklin MJ, Stewart PS. Role of antibiotic penetration limitation in Klebsiella pneumoniae biofilm resistance to ampicillin and ciprofloxacin. Antimicrob Agents Chemother. 2000;44:1818–24. CASPubMedPubMed CentralGoogle Scholar
  81. Vanzi V, Pitaro R. Skin injuries and chlorhexidine gluconate-based antisepsis in early premature infants: a case report and review of the literature. J Perinat Neonatal Nurs. 2018;32(4):341–50. PubMedGoogle Scholar
  82. Tanzer JM, Slee AM, Kamay BA. Structural requirements of guanide, biguanide, and bisbiguanide agents for antiplaque activity. Antimicrob Agents Chemother. 1977;12:721–9. CASPubMedPubMed CentralGoogle Scholar
  83. Bashir MH, Hollingsworth A, Schwab D, Prinsen KS, Paulson JE, Morse DJ, Bernatchez SF. Ex vivo and in vivo evaluation of residual chlorhexidine gluconate on skin following repetitive exposure to saline and wiping with 2% chlorhexidine gluconate/70% isopropyl alcohol pre-operative skin preparations. J Hosp Infect. 2019;102:256–61. CASPubMedGoogle Scholar
  84. Hann S, Hughes TM, Stone NM. Flexural allergic contact dermatitis to benzalkonium chloride in antiseptic bath oil. Br J Dermatol. 2007;157(4):795–8. CASPubMedGoogle Scholar
  85. Rohrer N, Widmer AF, Waltimo T, Kulik EM, Weiger R, Filipuzzi-Jenny E, Walter C. Antimicrobial efficacy of 3 oral antiseptics containing octenidine, polyhexamethylene biguanide, or citroxx: can chlorhexidine be replaced? Infect Control Hosp Epidemiol. 2010;31:733–9. PubMedGoogle Scholar
  86. Koburger T, Hübner N-O, Braun M, Siebert J, Kramer A. Standardized comparison of antiseptic efficacy of triclosan, PVP–iodine, Octenidine dihydrochloride, polyhexanide and chlorhexidine Digluconate. J Antimicrob Chemother. 2010;65:1712–9. CASPubMedGoogle Scholar
  87. Beaudouin E, Kanny G, Morisset M, Renaudin JM, Mertes M, Laxenaire MC, Mouton C, Jacson F, Moneret-Vautrin DA. Immediate hypersensitivity to chlorhexidine: literature review. Eur Ann Allergy Clin Immunol. 2004;36(4):123–6. CASPubMedGoogle Scholar
  88. Wessels S, Ingmer H. Modes of action of three disinfectant active substances: a review. Regul Toxicol Pharmacol. 2013;67(3):456–67. CASPubMedGoogle Scholar
  89. Krautheim AB, Jermann TH, Bircher AJ. Chlorhexidine anaphylaxis: case report and review of the literature. Contact Dermatitis. 2004;50:113–6. CASPubMedGoogle Scholar
  90. Darouiche RO, Wall MJ, Itani KM, Otterson MF, Webb AL, Carrick MM, Miller HJ, Awad SS, Crosby CT, Mosier MC, Alsharif A, Berger DH. Chlorhexidine-alcohol versus povidone-iodine for surgical-site antisepsis. N Engl J Med. 2010;362(1):18–26. CASPubMedGoogle Scholar
  91. Durani P, Leaper D. Povidone-iodine: use in hand disinfection, skin preparation and antiseptic irrigation. Int Wound J. 2008;5(3):376–87. PubMedPubMed CentralGoogle Scholar
  92. Wutzler P, Sauerbrei A, Klocking R, Brogmann B, Reimer K. Virucidal activity and cytotoxicity of the liposomal formulation of povidone-iodine. Antivir Res. 2002;54(2):89–97. CASPubMedGoogle Scholar
  93. Barreto R, Barrois B, Lambert J, Malhotra-Kumar S, Santos-Fernandes V, Monstrey S. Addressing the challenges in antisepsis: focus on povidone iodine. Int J Antimicrob Agents. 2020;56(3):106064. CASPubMedGoogle Scholar
  94. Capriotti KD, Anadkat M, Choi J, Kaffenberger B, McLellan B, Barone S, Kukoyi O, Goldfarb S, Lacouture M. A randomized phase 2 trial of the efficacy and safety of a novel topical povidone-iodine formulation for cancer therapy-associated paronychia. Investig New Drugs. 2019;37:1247–56. CASGoogle Scholar
  95. Bigliardi PL, Alsagoff SAL, El-Kafrawi HY, Pyon JK, Wa CTC, Villa MA. Povidone iodine in wound healing: a review of current concepts and practices. Int J Surg. 2017;44:260–8. PubMedGoogle Scholar
  96. Jalil A, Matuszczak B, Nguyen Le N-M, Mahmood A, Laffleur F, Bernkop-Schnürch A. Synthesis and characterization of thiolated pvp-iodine complexes: key to highly mucoadhesive antimicrobial gels. Mol Pharm. 2018;15:3527–34. CASPubMedGoogle Scholar
  97. Macias JH, Alvarez MF, Arreguin V, Muñoz JM, Macias AE, Alvarez JA. Chlorhexidine avoids skin bacteria recolonization more than triclosan. Am J Infect Control. 2016;44:1530–4. CASPubMedGoogle Scholar
  98. Lachapelle JM. Allergic contact dermatitis from povidone-iodine: a re-evaluation study. Contact Dermatitis. 2005;52(1):9–10. CASPubMedGoogle Scholar
  99. Sibbald RG, Coutts P, Woo KY. Reduction of bacterial burden and pain in chronic wounds using a new polyhexamethylene biguanide antimicrobial foam dressing-clinical trial results. Adv Skin Wound Care. 2011;24:78–84. PubMedGoogle Scholar
  100. Hübner NO, Kramer A. Review on the efficacy, safety and clinical applications of Polihexanide, a modern wound antiseptic. Skin Pharmacol Physiol. 2010;23:17–27. PubMedGoogle Scholar
  101. Yanai R, Ueda K, Nishida T, Toyohara M, Mori O. Effects of ionic and surfactant agents on the antimicrobial activity of polyhexamethylene biguanide. Eye Contact Lens. 2011;37:85–9. PubMedGoogle Scholar
  102. Krebs FC, Miller SR, Ferguson ML, Labib M, Rando RF, Wigdahl B. Polybiguanides, particularly polyethylene hexamethylene biguanide, have activity against human immunodeficiency virus type 1. Biomed Pharmacother. 2005;59:438–45. CASPubMedGoogle Scholar
  103. Valluri S, Fleming TP, Laycock KA, Tarle IS, Goldberg MA, Garcia-Ferrer FJ, Essary LR, Pepose JS. In vitro and in vivo effects of polyhexamethylene biguanide against herpes simplex virus infection. Cornea. 1997;16:556–9. CASPubMedGoogle Scholar
  104. Broxton P, Woodcock PM, Gilbert P. Injury and recovery of Escherichia coli ATCC 8,739 from treatment with some polyhexamethylene biguanides. Microbios. 1984;40:187–93. CASPubMedGoogle Scholar
  105. Harbs N, Siebert J. In vitro efficacy of octenidine and polihexanide against biofilms composed of Pseudomonas aeruginosa. GMS Krankenh Interdiszip. 2007;2:45. Google Scholar
  106. Olivieri J, Eigenmann PA, Hauser C. Severe anaphylaxis to a new disinfectant: polihexanide, a chlorhexidine polymer. Schweiz Med Wochenschr. 1998;128:1508–11. CASPubMedGoogle Scholar
  107. Ferrarini A, Baggi M, Fluckiger R, Bianchetti MG. Intraoperative anaphylaxis to a chlorhexdine polymer in childhood. Paediatr Anaesth. 2006;16:705. PubMedGoogle Scholar
  108. Storm-Versloot MN, Vos CG, Ubbink DT, Vermeulen H. Topical silver for preventing wound infection. Cochrane Database Syst Rev. 2010;3:CD006478. Google Scholar
  109. Vermeulen H, van Hattem J, Storm-Versloot MN, et al. Topical silver for treating infected wounds. Cochrane Database Syst Rev. 2007;1:CD005486. Google Scholar
  110. Graham C. The role of silver in wound healing. Br J Nurs. 2005;14:S22–8. PubMedGoogle Scholar
  111. Lo SF, Hayter M, Chang CJ, et al. A systematic review of silver-releasing dressings in the management of infected chronic wounds. J Clin Nurs. 2008;17:1973–85. PubMedGoogle Scholar
  112. Jung WK, Koo HC, Kim KW, Shin S, Kim SH, Park YH. Antibacterial activity and mechanism of action of the silver ion in Staphylococcus aureus and Escherichia coli. Appl Environ Microbiol. 2008;74:2171–8. CASPubMedPubMed CentralGoogle Scholar
  113. Randall CP, Gupta A, Jackson N, Busse D, O'Neill AJ. Silver resistance in Gram-negative bacteria: a dissection of endogenous and exogenous mechanisms. J Antimicrob Chemother. 2015;70(4):1037–46. CASPubMedPubMed CentralGoogle Scholar
  114. Lansdown A. Silver in health care: antimicrobial effects and safety in use. Curr Probl Dermatol. 2006;33:17–34. CASPubMedGoogle Scholar
  115. Panacek A, Kvitek L, Smekalova M, et al. Bacterial resistance to silver nanoparticles and how to overcome it. Nat Nanotechnol. 2018;13(1):65–71. CASPubMedGoogle Scholar
  116. Lansdown AB. A pharmacological and toxicological profile of silver as an antimicrobial agent in medical devices. Adv Pharmacol Sci. 2010;2010:910686. PubMedPubMed CentralGoogle Scholar
  117. Murphy EC, Friedman AJ. Hydrogen peroxide and cutaneous biology: translational applications, benefits, and risks. J Am Acad Dermatol. 2019;81(6):1379–86. CASPubMedGoogle Scholar
  118. Dukan S, Touati D. Hypochlorous acid stress in Escherichia coli: resistance, DNA damage, and comparison with hydrogen peroxide stress. J Bacteriol. 1996;178(21):6145–50. CASPubMedPubMed CentralGoogle Scholar
  119. Setlow B, Setlow P. Binding of small, acid-soluble spore proteins to DNA plays a significant role in the resistance of Bacillus subtilis spores to hydrogen peroxide. Appl Environ Microbiol. 1993;59(10):3418–23. CASPubMedPubMed CentralGoogle Scholar
  120. Zhou XQ, Xie WG. Research advances on the effect of hydrogen peroxide in wound healing. Zhonghua Shao Shang Za Zhi. 2020;36(11):1083–6. CASPubMedGoogle Scholar
  121. Iacopi E, Abbruzzese L, Goretti C, Riitano N, Piaggesi A. The use of a novel super-oxidized solution on top of standard treatment in the home care management of postsurgical lesions of the diabetic foot reduces reinfections and shortens healing time. Int J Low Extrem Wounds. 2018;17(4):268–74. PubMedGoogle Scholar
  122. Salisbury AM, Percival SL. The efficacy of an electrolysed water formulation on biofilms. Adv Exp Med Biol. 2019;1214:1–8. CASPubMedGoogle Scholar
  123. Piaggesi A, Goretti C, Mazzurco S, et al. A randomized controlled trial to examine the efficacy and safety of a new super-oxidized solution for the management of wide post-surgical lesions on the diabetic foot. Int J Low Extrem Wounds. 2010;9:10–5. CASPubMedGoogle Scholar
  124. Aragón-Sánchez J, Lázaro-Martínez JL, Quintana-Marrero Y, Sanz-Corbalán I, Hernández-Herrero MJ, Cabrera-Galván JJ. Super-oxidized solution (Dermacyn wound care) as adjuvant treatment in the postoperative management of complicated diabetic foot osteomyelitis: preliminary experience in a specialized department. Int J Low Extrem Wounds. 2013;12(2):130–7. PubMedGoogle Scholar
  125. D'Atanasio N, Capezzone de Joannon A, Mangano G, et al. A new acid-oxidizing solution: assessment of its role on methicillin-resistant Staphylococcus aureus (MRSA) biofilm morphological changes. Wounds. 2015;27(10):265–73. PubMedGoogle Scholar
  126. Ricci E. The management of chronic ulcers with an acidoxidising solution. J Wound Care. 2016;25(8):443–50. CASPubMedGoogle Scholar
  127. Hadi SF, Khaliq T, Bilal N, Sikandar I, Saaiq M, Zubair M, Aurangzeb S. Treating infected diabetic wounds with superoxidized water as anti-septic agent : a preliminary experience. J Coll Physicians Surg Pak. 2007;17(12):740–3. PubMedGoogle Scholar
  128. Martinez-De Jesus FR, Ramos De la Medina A, Remes-Troche JM, et al. Efficacy and safety of neutral pH superoxidised solution in severe diabetic foot infections. Int Wound J. 2007;4:353–62. PubMedPubMed CentralGoogle Scholar
  129. De Angelis B, Lucarini L, Agovino A, et al. Combined use of super-oxidized solution with negative pressure for the treatment of pressure ulcers: case report. Int Wound J. 2012;24 Google Scholar
  130. Bahari N, Hashim N, Md Akim A, Maringgal B. Recent advances in honey-based nanoparticles for wound dressing: a review. Nano. 2022;12:2560. CASGoogle Scholar
  131. Tashkandi H. Honey in wound healing: an updated review. Open Life Sci. 2021;16(1):1091–100. CASPubMedPubMed CentralGoogle Scholar
  132. Yilmaz AC, Aygin D. Honey dressing in wound treatment: a systematic review. Complement Ther Med. 2020;51:102388. PubMedGoogle Scholar
  133. Oryan A, Alemzadeh E, Moshiri A. Biological properties and therapeutic activities of honey in wound healing: a narrative review and meta-analysis. J Tissue Viability. 2016;25:98–118. PubMedGoogle Scholar
  134. Smaropoulos E, Cremers NAJ. Treating severe wounds in pediatrics with medical grade honey: a case series. Clin Case Rep. 2020;8:469–76. PubMedPubMed CentralGoogle Scholar
  135. Angioi R, Morrin A, White B. The rediscovery of honey for skin repair: recent advances in mechanisms for honeymediatedwound healing and scaffolded application techniques. Appl Sci. 2021;11:5192. CASGoogle Scholar
  136. Scepankova H, Combarros-Fuertes P, Fresno JM, Tornadijo ME, Dias MS, Pinto CA, Saraiva JA, Estevinho LM. Role of honey in advanced wound care. Molecules. 2021;26:4784. CASPubMedPubMed CentralGoogle Scholar
  137. Nolan VC, Harrison J, Cox JAG. Dissecting the antimicrobial composition of honey. Antibiotics. 2019;8:251. CASPubMedPubMed CentralGoogle Scholar
  138. Cebrero G, Sanhueza O, Pezoa M, Báez ME, Martínez J, Báez M, Fuentes E. Relationship among the minor constituents, antibacterial activity and geographical origin of honey: a multifactor perspective. Food Chem. 2020;315:126296. CASPubMedGoogle Scholar
  139. Yupanqui Mieles J, Vyas C, Aslan E, Humphreys G, Diver C, Bartolo P. Honey: an advanced antimicrobial and wound healing biomaterial for tissue engineering applications. Pharmaceutics. 2022;14:1663. CASPubMedPubMed CentralGoogle Scholar
  140. Critchfield JW, Butera ST, Folks TM. Inhibition of HIV activation in latently infected cells by flavonoid compounds. AIDS Res Hum Retrovir. 1996;12:39–46. CASPubMedGoogle Scholar

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Authors and Affiliations

  1. Diabetic Foot Section, Pisa University Hospital, Pisa, Italy Elisabetta Iacopi, Francesco Giangreco & Alberto Piaggesi
  1. Elisabetta Iacopi