Polyhexamethylene Biguanide (PHMB): An Addendum to Current Topical Antimicrobials
- 0 Comments
- 12314 reads
A review of the literature demonstrates in-vivo and in-vitro safety and effectiveness of PHMB for a number of applications. For wound dressings, Wright and colleagues26 compared the effectiveness of a silver dressing to a dry gauze dressing containing PHMB (Kerlix AMD). Results demonstrated reduction in bioburden with both dressings when tested in an in-vitro bactericidal assay. Using a Kirby-Bauer zone of inhibition study, the gauze was not as effective. This was believed to be due to a tight bond between the dressing and PHMB, which was not released and therefore did not result in killing beyond the edge of the dressing.26 Alternatively, Motta and associates6 demonstrated a good response using Kerlix AMD compared to gauze without PHMB in wounds where packing the dressing into the wound was required. Results suggested that the PHMB in the gauze resulted in a decrease in the number of organisms present in the wound.
The majority of literature describes effectiveness of PHMB on various microorganisms associated with contact lens disinfecting solutions. Antimicrobial effectiveness has been demonstrated on Acanthamoeba polyphaga, A castellanii, and A hatchetti.25,27,28 Additional effectiveness was demonstrated for PHMB use in water treatment. Barker and colleagues29 tested the effect of PHMB on Legionella pneumophila. This bacterium causes Legionnaire’s disease and can be found in water systems, air conditioning machinery, and cooling towers.
Gilbert and colleagues30,31 have performed numerous studies on bacteria, especially those that form biofilms, such as Klebsiella pneumoniae. In studying biofilms produced from E coli and S epidermidis, they noted that those compounds with higher activity against planktonic bacteria, including PHMB, were also the most effective agents against sessile bacteria found within biofilms. They suggested that the differences in effects of concentration of PHMB on planktonic versus sessile bacteria was due to either the mechanism of action or the number or disposition of cationic binding sites.30–32 Kramer et al33 have studied the effects of various antiseptics including PHMB on fibroblast proliferation and cytotoxicity. They noted that while octenidine-based products retarded wound healing, PHMB promoted contraction and aided wound closure significantly more than octenidine and placebo.
The mechanism of action of PHMB has been described in a number of articles. Broxton et al34,35 demonstrated that maximal activity of the PHMB occurs at between pH 5–6 and that initially the biocide interacts with the surface of the bacteria and then is transferred to the cytoplasm and cytoplasmic membrane. Ikeda and colleagues36 showed that the cationic PHMB had little effect on neutral phospholipids in the bacterial membrane—its effect was mainly on the acidic negatively charged species where it induced aggregation leading to increased fluidity and permeability. This results in the release of lipopolysaccharides from the outer membrane, potassium ion efflux, and eventual organism death.37
1. Atiyeh BS, Ioannovich J, Al-Amm CA, El-Musa KA. Management of acute and chronic open wounds: the importance of moist environment in optimal wound healing. Curr Pharm Biotechnol. 2002;3(3):179–195.
2. Enoch S, Harding K. Wound bed preparation: the science behind the removal of barriers to healing. WOUNDS. 2003;15(7):213–229.
3. Falanga V. Wound bed preparation: future approaches. Ostomy Wound Manage. 2003;49(5A Suppl):30–33.
4. Schultz GS, Sibbald RG, Falanga V, et al. Wound bed preparation: a systematic approach to wound management. Wound Repair Regen. 2003;11(Suppl 1):S1–S28.
5. Junkin J. Failure to thrive in wounds: prevention and early intervention. Infect Control Resource. 2003;1(2):1–6.
6. Motta GJ, Milne CT, Corbett LQ. Impact of antimicrobial gauze on bacterial colonies in wounds that require packing. Ostomy Wound Manage. 2004;50(8):48–62.
7. Kingsley A. The wound infection continuum and its application to clinical practice. Ostomy Wound Manage. 2003;49(7A Suppl):1–7.
8. Ovington L. Bacterial toxins and wound healing. Ostomy Wound Manage. 2003;49(7A Suppl):8–12.
9. Sibbald RG. Topical antimicrobials. Ostomy Wound Manage. 2003;49(5A Suppl):14–18.
10. Mertz PM. Cutaneous biofilms: friend or foe? WOUNDS. 2003;15(5):129–132.
11. Stotts NA. Wound infection: diagnosis and management. In: Bryant RA, ed. Acute and Chronic Wounds: Nursing Management. 2nd ed. St. Louis, MO: Mosby: 2000:179–188.
12. Fraser JF, Bodman J, Sturgess R, Faoagali J, Kimble RM. An in-vitro study of the antimicrobial efficacy of a 1% silver sulphadiazine and 0.2% chlorhexidine digluconate cream, 1% silver sulfadiazine cream and a silver coated dressing. Burns. 2004;30(1):35–41.
13. Burrell RE. A scientific perspective on the use of topical silver preparations. Ostomy Wound Manage. 2003;49(5A Suppl):19–24.
14. Drosou A, Falabella A, Kirsner RS. Antiseptics on wounds: an area of controversy. WOUNDS. 2003;15(5):149–166.
15. Tambe SM, Sampath L, Modak SM. In-vitro evaluation of the risk of developing bacterial resistance to antiseptics and antibiotics used in medical devices. J Antimicrob Chemother. 2001;47(5):589–598.
16. Ovington LG. The truth about silver. Ostomy Wound Manage. 2004;50(9A Suppl):1S–10S.
17. Parsons D, Bowler PG, Myles V, Jones S. Silver antimicrobial dressings in wound management: a comparison of antibacterial, physical, and chemical characteristics. WOUNDS. 2005;17(8):222–232.
18. Fox CL, Modak SM. Mechanism of silver sulfadiazine action on burn wound infections. Antimicrob Agents Chemother. 1974:5(6):582–588.
19. Hohaus K, Vennewald I, Wollina U. Deep mycosis caused by Trichophyton mentagrophytes in a diabetic patient. Mycoses. 2003;46(8):355–357.
20. Thomas S, McCubbin P. A comparison of the antimicrobial effects of four silver-containing dressings on three organisms. J Wound Care. 2003;12(3):101–107.
21. Thomas S, McCubbin P. An in-vitro analysis of the antimicrobial properties of 10 silver-containing dressings. J Wound Care. 2003;12(8):305–308.
22. Jones S, Bowler PG, Walker M. Antimicrobial activity of silver-containing dressings is influenced by dressing conformability with a wound surface. WOUNDS. 2005;17(9):263–270.
23. Mertz PM, Oliveira-Gandia MF, Davis SC. The evaluation of a cadexomer iodine wound dressing on methicillin resistant Staphylococcus aureus (MRSA) in acute wounds. Dermatol Surg.1999;25(2):89–93.
24. Hansson C. The effects of cadexomer iodine paste in the treatment of venous leg ulcers compared with hydrocolloid dressing and paraffin gauze dressing. Cadexomer Iodine Study Group. Int J Dermatol. 1998;37(5):390–396.
25. Hughes R, Heaselgrave W, Kilvington S. Acanthamoeba polyphaga strain age and method of cyst production influence the observed efficacy of therapeutic agents and contact lens disinfectants. Antimicrob Agents Chemother. 2003;47(10):3080–3084.
26. Wright JB, Lam K, Olson ME, Burrell RE. Is antimicrobial efficacy sufficient? A question concerning the benefits of new dressings. WOUNDS. 2003;15(5):133–142.
27. Burger RM, Franco RJ, Drlica K. Killing Acanthamoebae with polyaminopropyl biguanide: quantitation and kinetics. Antimicrob Agents Chemother. 1994;38(4):886–888.
28. Hiti K, Walochnik J, Haller-Schober EM, Faschinger C, Aspock H. Viability of Acanthamoeba after exposure to a multipurpose disinfecting contact lens solution and two hydrogen peroxide systems. Br J Ophthalmol. 2002;86(2):144–146.
29. Barker J, Brown MR, Collier PJ, Farrell I, Gilbert P. Relationship between Legionella pneumophila and Acanthamoeba polyphaga: physiological status and susceptibility to chemical inactivation. Appl Env Microbiol. 1992;58(8):2420–2425.
30. Gilbert P, Das JR, Jones MV, Allison DG. Assessment of resistance towards biocides following the attachment of micro-organisms to, and growth on, surfaces. J Appl Microbiol. 2001;91(2):248–254.
31. Gilbert P, Pemberton D, Wilkinson DE. Synergism within polyhexamethylene biguanide biocide formulations. J Appl Bacteriol. 1990;69(4):593–598.
32. Zhou XF, Markx GH, Pethig R, Eastwood IM. Differentiation of viable and non-viable bacterial biofilms using electrorotation. Biochim Biophys Acta. 1995;1245(1):85–93.
33. Kramer A, Roth B, Müller G, Rudolph P, Klocker N. Influence of the antiseptic agents polyhexanide and octenidine on FL cells and on healing of experimental superficial aseptic wounds in piglets. A double-blind, randomized, stratified, controlled, parallel-group study. Skin Pharmacol Physiol. 2004;17(3):141–146.
34. Broxton P, Woodcock PM, Gilbert P. Binding of some polyhexamethylene biguanides to the cell envelope of Escherichia coli ATCC 8739. Microbios. 1984;41(163):15–22.
35. Broxton P, Woodcock PM, Heatley F, Gilbert P. Interaction of some polyhexamethylene biguanides and membrane phospholipids in Escherichia coli. J Appl Bacteriol. 1984;57(1):115–124.
36. Ikeda T, Ledwith A, Bamford CH, Hann RA. Interaction of a polymeric biguanide biocide with phospholipids membranes. Biochim Biophys Acta. 1984;769(1):57–66.
37. Yasuda K, Ohmizo C, Katsu T. Potassium and tetraphenylphosphonium ion-selective electrodes for monitoring changes in the permeability of bacterial outer and cytoplasmic membranes. J Microbiol Methods. 2003;54(1):111–115.
38. Kramer A, Behrens-Baumann W. Prophylactic use of topical anti-infectives in ophthalmology. Ophthalmologica. 1997;211(Suppl 1):68–76.
39. Rosin M, Welk A, Kocher T, Majic-Todt A, Kramer A, Pitten FA. The effect of a polyhexamethylene biguanide mouthrinse compared to an essential oil rinse and a chlorhexidine rinse on bacterial counts and 4-day plaque regrowth. J Clin Periodontol. 2002;29(5):392–399.
40. Petrou-Binder S. PHMB-containing antiseptics ‘may offer alternative’ to iodine perioperative agents, say researchers. Available at: http://www.escrs.org/eurotimes/April2003/phmb.asp.
41. Reitsma AM, Rodeheaver GT. Effectiveness of a new antimicrobial gauze dressing as a bacterial barrier. Mansfield, Mass: Tyco Healthcare Group LP; 2001:1–4.
42. Orr R, Eggleston T, Shelanski MV. Determination of the irritating and sensitizing propensities of Kerlix® A.M.D. antimicrobial gauze dressing on scarified human skin. Mansfield, Mass: Tyco Healthcare Group LP; 2001:1–4.
43. Frankel VH, Serafica GC, Damien CJ. Development and testing of a novel biosynthesized XCell for treating chronic wounds. Surg Technol Int. 2004;12:27–33.
44. Alvarez OA, Patel M, Booker J, Markowitz L. Effectiveness of a biocellulose wound dressing for the treatment of chronic venous leg ulcers: results of a single center randomized study involving 24 patients. WOUNDS. 2004;16(7):224–233.
45. Phillips T, Stanton B, Provan A, Lew R. A study of the impact of leg ulcers on quality of life: financial, social, and psychological implications. J Am Acad Dermatol. 1994;31(1):49–53.
46. Mulder GD. Cost-effective managed care: gel versus wet-to-dry for debridement. Ostomy Wound Manage. 1995;41(2):68–74.