Antiseptics on Wounds: An Area of Controversy (PART TWO)

Anna Drosou, MD;(1) Anna Falabella, MD;(1) Robert S. Kirsner, MD(1,2)


Hydrogen Peroxide

A three-percent solution of hydrogen peroxide is commonly used as a wound antiseptic. The three-percent solution demonstrates in-vitro broad-spectrum efficacy. Its greatest activity is towards Gram-positive bacteria, but the presence of catalase in these bacteria makes dilutions below three percent less effective.[1] In a similar fashion, catalases present in tissues can render hydrogen peroxide even less bactericidal in vivo.[6] Although hydrogen peroxide is very commonly used, surprisingly few studies have been conducted to examine its effect on the wound healing process and its efficacy as a wound antiseptic.

Animal and human studies have shown hydrogen peroxide to have no negative effect on wound healing. Lineaweaver, et al.,[29] did not find retardation of reepithelization in a rat model after irrigation of the wound with three-percent hydrogen peroxide. However, at the in-vitro component of the same study, he found minimal bactericidal effect of hydrogen peroxide. Gruber, et al.,[52] found acceleration of reepithelization in a rat model and in a clinical trial. However, bullae were formed on or about the day of healing in most of the patients, suggesting possibly that hydrogen peroxide should not be used in newly formed epithelium.

In another study by Tur, et al.,[80] hydrogen peroxide was found to significantly increase the blood flow in ischemic ulcers in a guinea pig model. The increased blood flow may be due to new vessel formation through activation of metalloproteinases. Interestingly, the blood flow was increased even in places distant to the local application of hydrogen peroxide. No explanation was given for this finding. However, the authors found no difference in the wound-healing rate. This may be due to the limited sensitivity of the method they used to evaluate the clinical response (visual determination of the non-necrotic area).

In a clinical study evaluating the effectiveness of hydrogen peroxide on reducing the infection rate of appendectomy wounds, no toxic effects were found, but it was found to be ineffective.[81] Similarly, in another clinical study in human blister wounds contaminated with Staphylococcus aureus, hydrogen peroxide was found not to retard the healing but neither did it decrease bacterial load.[82]

In conclusion, hydrogen peroxide appears not to negatively influence wound healing, but it is also ineffective in reducing the bacterial count. However, it may be useful as a chemical debriding agent. The American Medical Association concluded that the effervescence of hydrogen peroxide might provide some mechanical benefit in loosening debris and necrotic tissue of the wound.[13]

Acetic Acid

Acetic acid is frequently used in wounds as a 0.25-percent or 0.5-percent solution. It is bactericidal against many Gram-positive and Gram-negative organisms, especially Pseudomonas aeruginosa. No delay of reepithelization has been found in animal and human models.[52] Although one study found that acetic acid initially delayed reepithelization, after the eighth day, this effect did not persist. In the same study, it was not shown to influence tensile wound strength.[29] In two human uncontrolled studies, acetic acid was found to be beneficial in wounds infected with Pseudomonas aeruginosa.[83,84] In a study with patients with venous leg ulcers,[85] gauze dressings wetted with acetic acid were shown to effectively decrease the number of Staphylococcus aureus and Gram-negative rods. Pseudomonas was not reduced significantly.

Although several in-vitro studies found acetic acid to be cytotoxic,[31,86] the in-vivo studies do not confirm these findings. The authors believe that acetic acid can continue being used topically in contaminated wounds where an agent is needed in order to eliminate the chances of infection.


Chlorhexidine has been commonly used in disinfectant and antiseptic solutions.



1. McDonnell G, Russell AD. Antiseptics and disinfectants: Activity, action and resistance. Clinical Microbiology Reviews 1999;12(1):147–79.
2. Taylor DM. Inactivation of unconventional agents of the transmissible degenerative encephalopathies. In: Russell AD, Hugo WB, Ayliffe GAJ (eds). Principles and Practice of Disinfection, Preservation and Sterilization, Third Edition. Oxford, England: Blackwell Science, 1999.
3. Niedner R. Cytotoxicity and sensitization of povidone iodine and other frequently used anti-infective agents. Dermatology 1997;195(Suppl 2):89–92.
4. 56 Federal Register 33644 at 33662.
5. Bergstrom N, Bennet MA, Carlson CE, et al. Clinical Practice Guideline Number 15: Treatment of Pressure Ulcers. Rockville, MD: US Department of Health and Human Services. Agency for Health Care Policy and Research; 1994. AHCPR Publication 95-0652.
6. Brown CD, Zitelli JA. A review of topical agents for wounds and methods of wounding. J Dermatol Surg Oncol 1993;19:732–7.
7. Rodeheaver G. Controversies in topical wound management. WOUNDS 1989;1:19–27.
8. Oberg MS, Lindsey D. Do not put hydrogen peroxide or povidone iodine on wounds. AJDC 1987;141:27–8.
9. Mayer DA, Tsapogas MJ. Povidone-iodine and wound healing: A critical review. WOUNDS 1993;5(1):14–23.
10. Goldenheim PD. An appraisal of povidone-iodine and wound healing. Postgrad Med J 1993;69(S3):S97–S105.
11. Dow G, Browne A, Sibbald RG. Infection in chronic wounds: Controversies in diagnosis and treatment. Ost/Wound Manang 1999;45(8):23–40.
12. Laato M, Niinikoski J, Lundberg C, et al. Inflammatory reaction in blood flow and experimental wounds inoculated with Staphylococcus aureus. Eur Surg Res 1988;20:33.
13. Rodeheaver GT. Wound cleansing, wound irrigation, wound disinfection. In: Krasner D, Kane D. Chronic Wound Care: A Clinical Source Book for Healthcare Professionals, Second Edition. Wayne, PA: Health Management Publications, Inc., 1997:97–108.
14. Bucknall T. The effect of local infection upon wound healing: An experimental study. Br J Surg 1980;67:851.
15. Robson M. Disturbances of wound healing. Ann Emerg Med 1988;1:1274.
16. Robson M, Stenberg B, Herggers J. Wound healing alterations caused by infection. Clin Plastic Surg 1990;17:485.
17. Gilchrist B, Reed C. The bacteriology of chronic venous ulcers treated with occlusive hydrocolloid dressings. Br J Dermatol 1989;121(3):337–44.
18. Eriksson G, Eklund A, Kallings L. The clinical significance of bacterial growth in venous leg ulcers. Scand J Infect Dis 1984;16:175–80.
19. Hermanns JF, Paquet P, Arrese JE, et al. La cytotoxicité bénéfique des antiseptiques. Rev Med Liege 1999;54(7):600–5.
20. Heggers JP. Defining infection in chronic wounds: Does it matter? J Wound Care 1998;7(8):389–92.
21. Elek SD. Experimental staphylococcal infections in the skin of man. Ann NY Acad Sci 1056;65:85–90.
22. Krizek TJ, Pobson MD, Kho E. Bacterial growth and skin graft survival. Surg Forum 1967;18:518.
23. Lookingbill DP, Miller SM, Knowles RC. Bacteriology of chronic leg ulcers. Arch Dermatol 1978;114:1765–8.
24. Bendy RH, Nuccio PA, Wolfe E, et al. Relationship of quantitative wound bacterial counts to healing of decubity: Effect of topical gentamicin. Antimicrob Agents Chemother 1964;147–55.
25. Mertz PM, Ovington LG. Wound healing microbiology. Dermatologic Clinics 1993;4:739–47.
26. Colsky AS, Kirsner RS, Kerdel FA. Analysis of antibiotics susceptibilities of skin wound flora of hospitalized dermatology patients. Arch Dermatol 1998;134:1006–9.
27. Fleischer W, Reimer K. Povidone-iodine in antisepsis: State of the art. Dermatology 1997;195(Suppl 2):3–9.
28. Payne DN, Gibson SAW, Lewis R. Antiseptics: A forgotten weapon in the control of antibiotic resistant bacteria in hospital and community settings. J Roy Soc Health 1998;118(1):18–22.
29. Lineaweaver W, Howard R, Soucy D, et al. Topical antimicrobial toxicity. Arch Surg 1985;120(3):267–70.
30. Greenberg L, Ingalls JW. Bactericide/leukocide ratio: A technique for the evaluation of disinfectants. J Am Pharmaceutical Association 1958;XLVII:531–3.
31. Cooper ML, Laxer JA, Hansbrough JF. The cytotoxic effects of commonly used topical antimicrobial agents on human fibroblasts and keratinocytes. J Trauma 1991;31(6):775–84.
32. Fleming A. The action of chemical and physiological antiseptics in a septic wound. Br J Surg 1919;7:99–129.
33. Mertz PM, Davis S, Brewer L, Franzen L. Can antimicrobials be effective without impairing wound healing? The evaluation of a cadexomer iodine ointment. WOUNDS 1994;6(6):184–93.
34. Skog E, Amesjo B, Troeng T, et al. A randomized trial comparing cadexomer iodine and standard treatment in the outpatient management of chronic venous ulcers. Brit Med J 1983;109:77–83.
35. Fleischer W, Reimer K. Povidone iodine in antisepsis—State of art. Dermatology 1997;195(Suppl 2):3–9.
36. Rodeheaver G, Bellamy W, Kody M, et al. Bactericidal activity and toxicity of iodine-containing solutions in wounds. Arch Surg 1982;117:181–5.
37. Howell JM, Stair TO, Howell AW, et al. The effect of scrubbing and irrigation with normal saline, povidone iodine, and cefazolin on wound bacterial counts in a guinea pig model. Am J Emerg Med 1993;11:134–8.
38. Georgiade NG, Harris WA. Open and closed treatment of burns with povidone iodine. Plast Reconstr Surg 1973;52(5):640–4.
39. Gravett A, Sterner S, Clinton JE, et al. A trial of povidone iodine in the prevention of infection in sutured lacerations. Ann Emerg Med 1987;16(2):167/47–171/51.
40. Piérard-Franchimont C, Paquet P, Arrese JE, et al. Healing rate and bacterial necrotizing vasculitis in venous leg ulcers. Dermatology 1997;194:383–7.
41. Viljanto J. Disinfection of surgical wounds without inhibition of wound healing. Arch Surg 1980;115:253–6.
42. Berkelman RL, Holland BW, Anderson RL. Increased bactericidal activity of dilute preparations of povidone iodine solutions. J Clin Microbiol 1982;15:635–9.
43. Lammers RL, Fourré M, Calahan ML, et al. Effect of povidone iodine and saline soaking on bacterial counts in acute, traumatic, contaminated wounds. Ann Emerg Med 1990;19(6):709/155–714/160.
44. Platt J, Bucknall RA. An experimental evaluation of antiseptic wound irrigation. J Hosp Infect 1984;5:181–8.
45. Eldrich RF, Custer J, Madden J, et al. Studies in management of the contaminated wound: III. Assessment of the effectiveness of irrigation with antiseptics agents. Am J Surg 1969;118:21–30.
46. Sindelar WF, Mason GR. Irrigation of subcutaneous tissue with povidone-iodine solution for prevention of surgical wound infections. Surg Gynecol Obstet 1979;148:227–31.
47. Kucan JO, Robson MC, Heggers JP, et al. Comparison of silver sulfadiazine, povidone iodine and physiologic saline in the treatment of chronic pressure ulcers. J Am Geriatr Soc 1981;XXIX(5):232–5.
48. Mertz PM, Oliveira-Gandia MF, Davis SC. The evaluation of a cadexomer iodine wound dressing on methicillin resistant Staphylococcus aureus in acute wounds. Dermatol Surg 1999;25:89–93.
49. Danielsen L, Cherry GW, Harding K, Rollman O. Cadexomer iodine in ulcers colonized by Pseudomonas aeruginosa. J Wound Care 1997;6(4):169–72.
50. Sullivan TP, Eaglstein WH, Davis SC, Mertz P. The pig as a model for human wound healing. Wound Repair Regen 2001;9(2):66–76.
51. Geronemus RG, Mertz PM, Eaglstein WH. Wound healing: The effects of topical antimicrobial agents. Arch Dermatol 1979;15:1311–4.
52. Gruber RP, Vistnes L, Pardoe R. The effect of commonly used antiseptics on wound healing. Plast Reconstr Surg 1975;55(4):472–6.
53. Kjolseth D, Frank JM, Barker JH, et al. Comparison of the effects of commonly used wound agents on epithelialization and neovascularization. J Am College Surgeons 1994 Sept;179:305–12.
54. Menton DN, Brown M. The effects of commercial wound cleansers on cutaneous wound healing in guinea pigs. WOUNDS 1994;6:21–7.
55. Mulliken JB, Healey NA, Glowacki J. Povidone iodine and tensile strength of wounds in rats. J Trauma 1980;20(4):323–4.
56. Kashayap A, Beezhold D, Wiseman J, Beck WC. Effect of povidone-iodine dermatologic ointment on wound healing. The American Surgeon 1995;61:486–91.
57. Niedner R, Schopf E. Inhibition of wound healing by antiseptics. Br J Dermatol 1986;115(Suppl 31):41–4.
58. MacRae SM, Brown B, Edelhauser HF. The corneal toxicity of presurgical antiseptics. Am J Ophthalmol 1984;97:221–32.
59. Niedner R. Cytotoxicity and sensitization of povidone-iodine and other frequently used anti-infective agents. Dermatology 1997;195(Suppl 2):89–92.
60. Hopf K, Grandy R, Stahl-Bayliss C, Fitzmartin R. The effect of betadine cream vs. silvadene cream on reepithelialization in uninfected experimental wounds. Proc Burn Assoc 1991;23:166.
61. Robins P, Day CL Jr, Lew RA. A multivariate analysis of factors affecting wound healing time. Dermatol Surg Oncol 1984;10:219–22.
62. De Kock M, van der Merwe AE, Swarts C. A comparative study of povidone iodine cream and silver sulfadiazine in the topical treatment of burns. In: Selwyn S (ed). Proceedings of The First Asian/Pacific Congress of Medicine Services. London, UK: Royal Society of Medicine Services, 1998:65–71.
63. Lee BY, Trainor FS, Thoden WR. Topical application of povidone-iodine in the management of decubitus and stasis ulcers. J Am Geriatr Soc 1979;27(7):302–6.
64. Knutson RA, Merbitz LA, Creekmore MA, et al. Use of sugar and povidone-iodine to enhance wound healing: Five years’ experience. Southern Medical Journal 1981;74(11):1329–35.
65. Steen M. Review of povidone iodine use in the treatment of burns. Postgrad Med J 1993;69(Suppl 3):S84–S92.
66. Zamora L. Chemical and microbiologic characteristics and toxicity of povidone iodine solutions. Am J Surg 1986;151:400–5.
67. Burks RI. Povidone iodine solution in wound treatment. Physical Therapy 1998;78(2):212–8.
68. Lamme EN, Gustafsson TO, Middelkoop E. Cadexomer iodine shows stimulation of epidermal regeneration in experimental full thickness wounds. Arch Dermatol Res 1998;290:18–24.
69. Laudanska H, Gustavson B. In-patient treatment of chronic varicose venous ulcers. A randomized trial of cadexomer iodine versus standard dressings. J Internat Med Research 1988;16:428–35.
70. Hillstrom L. Iodosorb compared to standard treatment in chronic venous ulcers—A multicenter study. Acta Chir Scand 1988;Suppl 544:53–6.
71. Skog E, Arnesjo B, Troeng T, et al. A randomized trial comparing cadexomer iodine and standard treatment in the out-patient management of chronic venous ulcers. Br J Dermatol 1983;109:77–83.
72. Holloway GA, Johansen KH, Barnes RW, Pierce GE. Multicenter trial of cadexomer iodine to treat venous stasis ulcers. Western J Med 1989;151(1):35–8.
73. Ormiston MC, Seymour MT J, Venn GE, Cohen RI, Fox JA. Controlled trial of Iodosorb in chronic venous ulcers. Br Med J 1985;291:308–10.
74. Harcup JW, Saul PA. A study of the effect of cadexomer iodine in the treatment of venous leg ulcers. Br J Clin Prac 1986;40(9):360–4.
75. Tarvainen K. Cadexomer iodine (Iodosorb) compared with dextranomer (Debrisan) in the treatment of chronic leg ulcers. Acta Chir Scand 1988;Suppl 544:57–9.
76. Hansson C. The effects of cadexomer iodine paste in the treatment of venous leg ulcers compared with hydrocolloid dressing and paraffin gauze dressing. Internat J Dermatol 1998;37:390–6.
77. Floyer C, Wilkinson JD. Treatment of venous leg ulcers with cadexomer iodine with particular reference to iodine sensitivity. Acta Chir Scand 1988;Suppl 544:60–1.
78. Apelqvist J, Ragnarson Tennvall G. Cavity foot ulcers in diabetic patients: A comparative study of cadexomer iodine and standard treatment. An economic analysis alongside a clinical trial. Acta Derm Venereol 1996;76(3):231–5.
79. Moberg S, Hoffman L, Grennert ML, Holst A. A randomized trial of cadexomer iodine in decubitus ulcers. J Am Geriatrics Soc 1983;31(8):462–5.
80. Tur E, Bolton L, Constantine BE. Topical hydrogen peroxide treatment of ischemic ulcers in the guinea pig: Blood recruitment in multiple skin sites. JAAD 1995;33(2:1):217–21.
81. Lau WY, Wong SH. Randomised, prospective trial of topical hydrogen peroxide in appendectomy wound infection. Am J Surg 1981;142:393–7.
82. Leyden JJ, Bartelt NM. Comparison of topical antibiotic ointments, a wound protectant and antiseptics in the treatment of human blister wounds contaminated with Staphylococcus aureus. J Fam Pract 1987;24(6):601–4.
83. Phillips I, Lobo AZ, Fernadez R, Gundara NS. Acetic acid in the treatment of superficial wounds infected by Pseudomonas aeruginosa. Lancet 1968;1:11–3.
84. Sloss JM, Cumberland N, Milner SM. Acetic acid used for the elimination of Pseudomonas aeruginosa from burn and soft tissue wounds. J R Army Med Corps 1993;139(2):49–51.
85. Hansson C, Faergemann J. The effect of antiseptic solutions on microorganisms in venous leg ulcers. Acta Derm Venereol 1995;75(1):31–3.
86. Lineaweaver W, McMorris S, Soucy D, Howard R. Cellular and bacterial toxicities of topical antimicrobials. Plast Reconstr Surg 1985;75:394–6.
87. Saatman RA, Carlton WW, Hubben K, et al. A wound healing study of chlorhexidine digluconate in guinea pigs. Fundamental & Applied Toxicology 1986;6(1):1–6.
88. Sanchez IR, Swaim SF, Nusbaum KE, et al. Effects of chlorhexidine diacetate and povidone iodine on wound healing in dogs. Vet Surg 1988;17(6):291–5.
89. Severyns AM, Lejeune A, Rocoux G, Lejeune G. Non-toxic antiseptic irrigation with chlorhexidine in experimental revascularization in the rat. J Hosp Infect 1991;17:197–206.
90. Mobacken H, Wengstrom C. Interference with healing of rat skin incisions treated with chlorhexidine. Acta Dermatoveener (Stockholm) 1974;54:29–34.
91. Brennan SS, Foster ME, Leaper DJ. Antiseptic toxicity in wounds healing by secondary intention. J Hosp Infect 1986;8(3):263–7.
92. Shahan MH, Chuang AH, Brennan WA, et al. The effect of chlorhexidine irrigation on the tensile wound strength. J Periodontol 1993;64(8):719–22.
93. Lambert PM, Moris HF, Ochi S. The influence of 0.12% chlorhexidine gluconate rinses on the incidence of infectious complications and implant success. J Oral Maxillofac Surg 1997;55(12 Suppl 5):25–30.
94. Crossfill M, Hall R, London D. The use of chlorhexidine antisepsis in contaminated surgical wounds. Brit J Surg 1969;56(12):906–8.
95. Klasen HJ. A historical review of the use of silver in the treatment of burns. II. Renewed interest for silver. Burns 2000;26(2):131–8.
96. Monafo WW, West MA. Current treatment recommendations for topical burn therapy. Drugs 1990 Sep;40(3):364–73.
97. De Gracia CG. An open study comparing topical silver sulfadiazine and topical silver sulfadiazine-cerium nitrate in the treatment of moderate and severe burns. Burns 2001 Feb;27(1):67–74.
98. Tredget EE, Shankowsky HA, Groeneveld A, Burrell R. A matched-pair, randomized study evaluating the efficacy and safety of Acticoat silver-coated dressing for the treatment of burn wounds. J Burn Care Rehabil 1998;19(6):531–7.
99. Demling RH, DeSanti L. Effects of silver on wound management. WOUNDS 2001;13(1):5–15.
100. Lansdown AB, Sampson B, Laupattarakasem P, Vuttivirojana A. Silver aids healing in the sterile skin wound: Experimental studies in the laboratory rat. Br J Dermatol 1997;137(5):728–35.
101. Leitch IO, Kucukcelebi A, Robson MC. Inhibition of wound contraction by topical antimicrobials. Aust N Z J Surg 1993 Apr;63(4):289–93.
102. Bishop JB, Phillips LG, Mustoe TA, et al. A prospective randomized evaluator-blinded trial of two potential wound healing agents for the treatment of venous stasis ulcers. J Vasc Surg 1992 Aug;16(2):251–7.
103. Ouvry PA. [A trial of silver sulfadiazine in the local treatment of venous ulcer]. Phlebologie 1989 Nov-Dec;42(4):673–9.
104. Livingstone DH, Cryer HG, Miller FB, et al. A randomized prospective study of topical antimicrobial agents on skin grafts after thermal injury. Plast Reconstruct Surg 1990;86(6):1059–64.
105. Demling RH, DeSanti L. The rate of reepithelialization across meshed skin grafts is increased with exposure to silver. Burns 2002;28(3):264–6.
106. Olson ME, Wright JB, Lam K, Burrell RE. Healing of porcine donor sites covered with silver-coated dressings. Eur J Surg 2000;166:486–9.
107. Bennett LL, Rosenblum RS, Perlov C, et al. An in vivo comparison of topical agents on wound repair. Plast Reconstruct Surg 2001;108(3):675–85.
108. Mertz PM, Alvarez OM, Smerbeck RV, Eaglstein WH. A new in vivo model for the evaluation of topical antiseptics on superficial wounds. Arch Dermatol 1984;120:58–62.
109. Brennan SS, Leaper DJ. The effect of antiseptics on the healing wound: A study using the rabbit ear chamber. Br J Surg 1985;72:780–2.
110. Fumal I, Braham C, Paquet P, Pierard-Franchimont C, Pierard GE. The beneficial toxicity paradox of antimicrobials in leg ulcer healing impaired by a polymicrobial flora: A proof-of-concept study. Dermatology 2002;204(Suppl 1):70–4.
111. Hutchinson JJ, McGuckin M. Occlusive dressings: A microbiologic and clinical review. Am J Infect Control 1990;18(4):257–68.

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