Journal Mobile Options
Table of Contents
Vol. 23, Suppl. 1, 2010
Issue release date: September 2010
Free Access
Skin Pharmacol Physiol 2010;23(suppl 1):7–16
(DOI:10.1159/000318237)

Polihexanide: A Safe and Highly Effective Biocide

Kaehn K.
K2 Hygiene Dienstleistungen, Aschaffenburg, Germany
email Corresponding Author

Abstract

Polihexanide is a broad-spectrum antiseptic with excellent tolerance and a low-risk profile. The physicochemical action on the bacterial envelope prevents or impedes the development of resistant bacterial strains. Thus, polihexanide is particularly suitable and useful in the struggle against multidrug-resistant bacteria. The ecological database is still incomplete. There is some evidence that biodegradation requires adsorption to inert surfaces and that only a small number of bacterial species are capable of utilizing polihexanide.


 goto top of outline Key Words

  • Polihexanide
  • Polihexanide, chemical characteristics
  • Biocide
  • Antiseptic
  • Wounds

 goto top of outline Abstract

Polihexanide is a broad-spectrum antiseptic with excellent tolerance and a low-risk profile. The physicochemical action on the bacterial envelope prevents or impedes the development of resistant bacterial strains. Thus, polihexanide is particularly suitable and useful in the struggle against multidrug-resistant bacteria. The ecological database is still incomplete. There is some evidence that biodegradation requires adsorption to inert surfaces and that only a small number of bacterial species are capable of utilizing polihexanide.

Copyright © 2010 S. Karger AG, Basel


 goto top of outline References
  1. Davies GE, Francis J, Martin AR, Rose FL, Swain G: 1:6-Di-4′-chlorophenyldiguanidohexane (‘hibitane’); laboratory investigation of a new antibacterial agent of a high potency. Br J Pharmacol Chemother 1954;9:192–196.
  2. Willenegger H: Lokale Antiseptika in der Chirurgie – eine Wiedergeburt? Unfallchirurg 1994;20:94–110.
  3. Willenegger H: Klinische Erfahrungen mit einem neuen Antiinfektivum. Hyg Med 1994;19:227–233.
  4. Kaehn K, Eberlein T: Polyhexanide (PHMB) and betaine in wound care management. EWMA J 2008;8:13–17.
  5. Daeschlein G, Assadian O, Bruck JC, Meinl C, Kramer A, Koch S: Feasibility and clinical applicability of polihexanide for treatment of second-degree burn wounds. Skin Pharmacol Physiol 2007;20:292–296.
  6. Gerli S, Rossetti D, Di Renzo GC: A new approach for the treatment of bacterial vaginosis: use of polyhexamethylene biguanide. A prospective, randomized study. Eur Rev Med Pharmacol Sci 2003;7:127–130.
  7. Hansmann F, Kramer A, Ohgke H, Strobel H, Geerling G: Polyhexamethylbiguanid (PHMB) zur präoperativen Antisepsis bei Cataract Operation. Ophthalmologe 2004;101:377–383.
  8. Kramer A, Daeschlein G, Kammerlander G, Andriessen A, Aspöck C, Bergemann R, Eberlein T, Gerngross H, Görtz G, Heeg P, Jünger M, Koch S, König B, Laun R, Peter RU, Roth B, Ruef C, Sellmer W, Wewalka G, Eisenbeiss W: Konsensusempfehlung zur Auswahl von Wirkstoffen für die Wundantiseptik. Hyg Med 2004;5:147–157.
  9. Ikeda T, Tazuke S, Watanabe M: Interaction of biologically active molecules with phospholipid membranes. Fluorescence depolarisation studies on the effect of polymeric biocide bearing biguanides in the main chain. Biochim Biophys Acta 1983;735:380–386.
  10. Ikeda T, Ledwith A, Bamford CH, Hann RA: Interaction of polymeric biguanide biocide with phospholipid membranes. Biochim Biophys Acta 1984;769:57–66.
  11. Ikeda T, Tazuke S, Bamford CH: Interaction of membrane active biguanides with negatively charged species. A model of their interaction with target sites in microbial membranes. J Chem Res 1985;6:180–181.
  12. Ikeda T, Tazuke S, Bamford CH, Ledwith A: Spectroscopic studies on the interaction of polymeric in-chain biguanide biocide with phospholipid membranes as probed by 8-anilinonaphthalene-1-sulphonate. Bull Chem Soc Jpn 1985;58:705–709.
  13. Kramer A: Stellenwert der Infektionsprophylaxe und -therapie mit lokalen Antiinfektiva; in Kramer A, Wendt M,. Werner HP (eds): Möglichkeiten und Perspektiven der klinischen Antiseptik. Wiesbaden, mhp, 1995, pp 15–25.
  14. Frieling H, Gründling M, Lauer KS, Wendt M, Hackenberg T, Lehmann C, Pavlovic D: Intraperitoneal instillation of polihexanide produces hypotension and vasodilation: in vivo and in vitro study in rats. Int J Colorectal Dis 2006;21:373–383.

    External Resources

  15. Berg A, Assadian O, Rudolph P, Mundkowski RG, Janda J, Kramer A: Intolerability to Lavasept® peritoneal lavage in experimentally induced peritonitis in the guinea pig. Hyg Med 2008;33:189–193.
  16. Kramer A, Roth B, Müller G, Rudolph P, Klöcker N: Influence of the antiseptic agents polihexanide and octenidine on FL cells and on healing of experimental superficial aseptic wounds in piglets. A double-blind, randomised, stratified, controlled, parallel-group study. Skin Pharmacol Physiol 2004;17:141–146.
  17. Körber A, Dissemond J: Polyhexanid schützt vor Kollagendegradierung: Erste Resultate einer in vitro Untersuchung zu Koll-P-10. ZfW 2007;4:213–216.
  18. 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;9:449–454.
  19. Rose FL, Swain G: Bisdiguanides having antibacterial activity. J Chem Soc 1956;850:4422–4425.

    External Resources

  20. Bratt H, Hathway DE: Characterization of the urinary polymer-related material from rats given poly[biguanide-1,5-diylhexamethylene hydrochlorid]. Macromol Chem Phys 1976;177:2591–2605.
  21. O’Malley LP, Hassan KZ, Brittan H, Johnson N, Collins AN: Characterization of the biocide polyhexamethylene biguanide by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. J Appl Polym Sci Symp 2006;102:4928–4936.
  22. Kurzer F, Pitchfork ED: Biguanides. Berlin, Springer, 1968.
  23. Davies A, Bentley M, Field BS: Comparison of the action of vantocil, cetrimide and chlorhexidine on Escherichia coli and its spheroplasts and the protoplasts of gram-positive bacteria. J Appl Bacteriol 1968;31:448–461.
  24. Kramer A, Roth B: Polihexanid; in Kramer A, Assadian O (eds): Wallhäussers Praxis der Sterilisation, Desinfektion, Antiseptik und Konservierung. Qualitätssicherung der Hygiene in Industrie, Pharmazie und Medizin. Stuttgart, Thieme, 2008, pp 789–793.
  25. Broxton P, Woodcock PM, Heatley F, Gilbert P: Interaction of some polyhexamethylene biguanides and membrane phospholipids in Escherichia coli. J Appl Bacteriol 1984;57:115–124.
  26. Gilbert P, Pemberton D, Wilkinson DE: Barrier properties of gram-negative cell envelope towards high molecular weight polyhexamethylene biguanides. J Appl Bacteriol 1990;69:585–592.
  27. Gilbert P, Pemberton D, Wilkinson DE: Synergism within polyhexamethylene biguanide biocide formulations. J Appl Bacteriol 1990;69:593–598.
  28. 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;54:111–115.
  29. Allen MJ, White GF, Morby AP: The response of Escherichia coli to exposure to the biocide polyhexamethylene biguanide. Microbiology 2006;152:989–1000.
  30. Glukhov E, Stark M, Burrows LL, Deber CM: Basis for selectivity of cationic antimicrobial peptides for bacterial versus mammalian membranes. J Biol Chem 2005;280:33960–33967.
  31. Singer SJ, Nicolson GL: The fluid mosaic model of the structure of cell membranes. Science 1972;175:720–731.
  32. Zhu S: Evidence for myxobacterial origin of eukaryotic defensins. Immunogenetics 2007;59:949–954.
  33. Smith JG, Nemerow GR: Mechanism of adenovirus neutralization by Human alpha-defensins. Cell Host Microbe 2008;3:11–19.
  34. Taylor K, Clarke DJ, McCullough B, Chin W, Seo E, Yang D, Oppenheim J, Uhrin D, Govan JR, Campopiano DJ, MacMillan D, Barran P, Dorin JR: Analysis and separation of residues important for the chemoattractant and antimicrobial activities of beta-defensin 3. J Biol Chem 2008;283:6631–6639.
  35. Krishnakumari V, Nagaraj R: Interaction of antibacterial peptides spanning the carboxy-terminal region of human beta-defensins 1–3 with phospholipids at the air-water interface and inner membrane of E. coli. Peptides 2008;29:7–14.
  36. Vylkova S, Sun JN, Edgerton M: The role of released ATP in killing Candida albicans and other extracellular microbial pathogens by cationic peptides. Purinergic Signal 2007;3:91–97.
  37. Sugiarto H, Yu PL: Mechanisms of action of ostrich beta-defensins against Escherichia coli. FEMS Microbiol Lett 2007;270:195–200.
  38. Morgera F, Antcheva N, Pacor S, Quaroni L, Berti F, Vaccari L, Tossi A: Structuring and interactions of human beta-defensins 2 and 3 with model membranes. J Pept Sci 2008;14:518–523.
  39. Donlan RM: Biofilms: microbial life on surfaces. Emerg Infect Dis 2002;8:881–890.
  40. Gjødsbøl K, Christensen JJ, Karlsmark T, Jørgensen B, Klein BM, Krogfelt KA: Multiple bacterial species reside in chronic wounds: a longitudinal study. Int Wound J 2006;1:1–2.
  41. Bjarnsholt T, Kirketerp-Møller K, Jensen PØ, Madsen KG, Phipps R, Krogfelt K, Høiby N, Givskov M: Why chronic wounds will not heal: a novel hypothesis. Wound Repair Regen 2008;16:2–10.

    External Resources

  42. Seipp HM, Hofmann S, Hack A, Skowronsky A, Hauri A: Efficacy of various wound irrigation solutions against biofilms. ZfW 2005;4:160–164.
  43. Blackburn RS, Harvey A, Kettle LL, Payne JD, Russell SJ: Sorption of poly(hexamethylene biguanide) on cellulose: mechanism of binding and molecular recognition. Langmuir 2006;22:5636–5644.
  44. Kusnetsov JM, Tulkki AI, Ahonen HE, Martikainen PJ: Efficacy of tree prevention strategies against Legionella in cooling water systems. J Appl Microbiol 1997;82:763–768.
  45. Perez R, Davis SC, Kaehn K: Wirkung verschiedener Wundspüllösungen auf MRSA-Biofilme in Wunden im Tiermodel. WundManagement 2010,4:44–48.
  46. Elsztein C, de Menezes JAS, de Morais MA Jr: Polyhexamethyl biguanide can eliminate contaminant yeasts from fuel-ethanol fermentation process. J Ind Microbiol Biotechnol 2008;35:967–973.
  47. Messick CR, Pendland SL, Moshirfar M, Fiscella RG, Losnedahl KJ, Schriever CA, Schreckenberger PC: In-vitro activity of polyhexamethylene biguanide (PHMB) against fungal isolates associated with infective keratitis. J Antimicrob Chemother 1999;44:297–298.
  48. Liu N, Khong D, Chung SK, Hwang DG: In-vitro susceptibility of ocular bacterial and fungal pathogens to polyhexamethylene biguanide. Invest Ophthamol Vis Sci 1996;37:4058.

    External Resources

  49. Larkin DFP, Kilvington S, Dart JKG: Treatment of Acanthamoeba keratitis with polyhexamethylene biguanide. J Ophthalmol 1992;99:185–191.
  50. Donoso R, Mura JJ, Lopez M: Acanthamoeba keratitis treated with propamidine and polyhexamethylene biguanide (PHMB). Rev Med Chil 2002;130:396–401.
  51. Narasimhan S, Madhavan HN, Therese LK: Development and application of an in vitro susceptibility test for Acanthamoeba species isolated from keratitis to polyhexamethylene biguanide and chlorhexidine. Cornea 2002;21:203–205.

    External Resources

  52. 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;59:438–445.
  53. Andriessen AE, Eberlein T: Assessment of a wound cleansing solution in the treatment of problem wounds. Wounds 2008;20:171–175.
  54. Möller A, Kaehn K, Nolte A: Erfahrungen mit dem Einsatz polyhexanidhaltiger Wundprodukte bei der Versorgung chronischer Wunden – Ergebnisse einer systematischen retrospektiven Untersuchung an 953 Patienten. WundManagement 2008;3:112–117.
  55. Cazzaniga A, Serralta V, Davis S, Orr R, Eaglestein W, Mertz PM: The effect of an antimicrobial gauze dressing impregnated with 0.2 percent polyhexamethylene biguanides as a barrier to prevent Pseudomonas aeruginosa wound invasion. Wounds 2002;14:169–176.
  56. United States Environmental Protection Agency: Reregistration eligibility decision of PHMB. EPA739-R-05-003, September 2005.
  57. 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 re-growth. J Clin Periodontol 2002;98:392–399.

    External Resources

  58. Brecx M, Decker EM, Freitag HP, Maier G, von Ohle C: The effect of polihexanide on dental biofilm formation in vivo. J Dent Res 2008;87:0528.
  59. Christiansen R, Palmork KH: Distribution and elimination of [14C] in saithe (Pollachius virens L.) after application of a single dose of [14C] polyhexamethylene hydrochloridbiguanide. Bull Environ Contam Toxicol 1996;36:121–128.

    External Resources

  60. Zöllner H, Kramer A, Youssef P, Youssef U, Adrian V: Preliminary investigations on the biodegradability of selected microbicidal agents. Hyg Med 1995;20:401–407.
  61. O’Malley LP, Collins AN, White GF: Biodegradability of end-groups of the biocide polyhexamethylene biguanide (PHMB) assessed using model compounds. J Ind Microbiol Biotechnol 2006;33:677–684.
  62. O’Malley LP, Shaw CH, Collins AN: Microbial degradation of the biocide polyhexamethylene biguanide: isolation and characterization of enrichment consortia and determination of degradation by measurement of stable isotope incorporation into DNA. J Appl Microbiol 2007;103:1158–1169.
  63. Kawai F: Sphingomonads involved in the biodegradation of xenobiotic compounds. J Ind Microbiol Biotechnol 1999;23:400–407.
  64. Hiraishi T, Kajiyama M, Yamoto I, Doi Y: Enzymatic hydrolysis of alpha- and beta-oligo(L-aspartic acid) by poly(aspartic acid) hydrolases-1 and 2 from Sphingomonas sp. KT-1. Macromol Biosci 2004;4:330–339.
  65. Vacca DJ, Bleam WF, Hickey WJ: Isolation of soil bacteria adapted to degrade humic acid-sorbed phenanthrene. Appl Environ Microbiol 2005;71:3797–3805.
  66. Mishima Y, Momma K, Hashimoto W, Mikami B, Murata K: Super-channel in bacteria: function and structure of the macromolecule import system mediated by a pit-dependent ABC transporter. FEMS Microbiol Lett 2001;204:215–221.

 goto top of outline Author Contacts

Kurt Kaehn, MSc, PhD
K2 Hygiene Dienstleistungen
Haidstrasse 48
DE–67431 Aschaffenburg (Germany)
Tel. +49 602 144 7528, Fax + 49 602 144 7549, E-Mail k2-hygiene@t-online.de


 goto top of outline Article Information

Published online: September 8, 2010
Number of Print Pages : 10
Number of Figures : 1, Number of Tables : 3, Number of References : 66


 goto top of outline Publication Details

Skin Pharmacology and Physiology (Journal of Pharmacological and Biophysical Research)

Vol. 23, No. Suppl. 1, Year 2010 (Cover Date: September 2010)

Journal Editor: Lademann J. (Berlin)
ISSN: 1660-5527 (Print), eISSN: 1660-5535 (Online)

For additional information: http://www.karger.com/SPP


Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Abstract

Polihexanide is a broad-spectrum antiseptic with excellent tolerance and a low-risk profile. The physicochemical action on the bacterial envelope prevents or impedes the development of resistant bacterial strains. Thus, polihexanide is particularly suitable and useful in the struggle against multidrug-resistant bacteria. The ecological database is still incomplete. There is some evidence that biodegradation requires adsorption to inert surfaces and that only a small number of bacterial species are capable of utilizing polihexanide.



 goto top of outline Author Contacts

Kurt Kaehn, MSc, PhD
K2 Hygiene Dienstleistungen
Haidstrasse 48
DE–67431 Aschaffenburg (Germany)
Tel. +49 602 144 7528, Fax + 49 602 144 7549, E-Mail k2-hygiene@t-online.de


 goto top of outline Article Information

Published online: September 8, 2010
Number of Print Pages : 10
Number of Figures : 1, Number of Tables : 3, Number of References : 66


 goto top of outline Publication Details

Skin Pharmacology and Physiology (Journal of Pharmacological and Biophysical Research)

Vol. 23, No. Suppl. 1, Year 2010 (Cover Date: September 2010)

Journal Editor: Lademann J. (Berlin)
ISSN: 1660-5527 (Print), eISSN: 1660-5535 (Online)

For additional information: http://www.karger.com/SPP


Copyright / Drug Dosage

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

References

  1. Davies GE, Francis J, Martin AR, Rose FL, Swain G: 1:6-Di-4′-chlorophenyldiguanidohexane (‘hibitane’); laboratory investigation of a new antibacterial agent of a high potency. Br J Pharmacol Chemother 1954;9:192–196.
  2. Willenegger H: Lokale Antiseptika in der Chirurgie – eine Wiedergeburt? Unfallchirurg 1994;20:94–110.
  3. Willenegger H: Klinische Erfahrungen mit einem neuen Antiinfektivum. Hyg Med 1994;19:227–233.
  4. Kaehn K, Eberlein T: Polyhexanide (PHMB) and betaine in wound care management. EWMA J 2008;8:13–17.
  5. Daeschlein G, Assadian O, Bruck JC, Meinl C, Kramer A, Koch S: Feasibility and clinical applicability of polihexanide for treatment of second-degree burn wounds. Skin Pharmacol Physiol 2007;20:292–296.
  6. Gerli S, Rossetti D, Di Renzo GC: A new approach for the treatment of bacterial vaginosis: use of polyhexamethylene biguanide. A prospective, randomized study. Eur Rev Med Pharmacol Sci 2003;7:127–130.
  7. Hansmann F, Kramer A, Ohgke H, Strobel H, Geerling G: Polyhexamethylbiguanid (PHMB) zur präoperativen Antisepsis bei Cataract Operation. Ophthalmologe 2004;101:377–383.
  8. Kramer A, Daeschlein G, Kammerlander G, Andriessen A, Aspöck C, Bergemann R, Eberlein T, Gerngross H, Görtz G, Heeg P, Jünger M, Koch S, König B, Laun R, Peter RU, Roth B, Ruef C, Sellmer W, Wewalka G, Eisenbeiss W: Konsensusempfehlung zur Auswahl von Wirkstoffen für die Wundantiseptik. Hyg Med 2004;5:147–157.
  9. Ikeda T, Tazuke S, Watanabe M: Interaction of biologically active molecules with phospholipid membranes. Fluorescence depolarisation studies on the effect of polymeric biocide bearing biguanides in the main chain. Biochim Biophys Acta 1983;735:380–386.
  10. Ikeda T, Ledwith A, Bamford CH, Hann RA: Interaction of polymeric biguanide biocide with phospholipid membranes. Biochim Biophys Acta 1984;769:57–66.
  11. Ikeda T, Tazuke S, Bamford CH: Interaction of membrane active biguanides with negatively charged species. A model of their interaction with target sites in microbial membranes. J Chem Res 1985;6:180–181.
  12. Ikeda T, Tazuke S, Bamford CH, Ledwith A: Spectroscopic studies on the interaction of polymeric in-chain biguanide biocide with phospholipid membranes as probed by 8-anilinonaphthalene-1-sulphonate. Bull Chem Soc Jpn 1985;58:705–709.
  13. Kramer A: Stellenwert der Infektionsprophylaxe und -therapie mit lokalen Antiinfektiva; in Kramer A, Wendt M,. Werner HP (eds): Möglichkeiten und Perspektiven der klinischen Antiseptik. Wiesbaden, mhp, 1995, pp 15–25.
  14. Frieling H, Gründling M, Lauer KS, Wendt M, Hackenberg T, Lehmann C, Pavlovic D: Intraperitoneal instillation of polihexanide produces hypotension and vasodilation: in vivo and in vitro study in rats. Int J Colorectal Dis 2006;21:373–383.

    External Resources

  15. Berg A, Assadian O, Rudolph P, Mundkowski RG, Janda J, Kramer A: Intolerability to Lavasept® peritoneal lavage in experimentally induced peritonitis in the guinea pig. Hyg Med 2008;33:189–193.
  16. Kramer A, Roth B, Müller G, Rudolph P, Klöcker N: Influence of the antiseptic agents polihexanide and octenidine on FL cells and on healing of experimental superficial aseptic wounds in piglets. A double-blind, randomised, stratified, controlled, parallel-group study. Skin Pharmacol Physiol 2004;17:141–146.
  17. Körber A, Dissemond J: Polyhexanid schützt vor Kollagendegradierung: Erste Resultate einer in vitro Untersuchung zu Koll-P-10. ZfW 2007;4:213–216.
  18. 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;9:449–454.
  19. Rose FL, Swain G: Bisdiguanides having antibacterial activity. J Chem Soc 1956;850:4422–4425.

    External Resources

  20. Bratt H, Hathway DE: Characterization of the urinary polymer-related material from rats given poly[biguanide-1,5-diylhexamethylene hydrochlorid]. Macromol Chem Phys 1976;177:2591–2605.
  21. O’Malley LP, Hassan KZ, Brittan H, Johnson N, Collins AN: Characterization of the biocide polyhexamethylene biguanide by matrix-assisted laser desorption ionization time-of-flight mass spectrometry. J Appl Polym Sci Symp 2006;102:4928–4936.
  22. Kurzer F, Pitchfork ED: Biguanides. Berlin, Springer, 1968.
  23. Davies A, Bentley M, Field BS: Comparison of the action of vantocil, cetrimide and chlorhexidine on Escherichia coli and its spheroplasts and the protoplasts of gram-positive bacteria. J Appl Bacteriol 1968;31:448–461.
  24. Kramer A, Roth B: Polihexanid; in Kramer A, Assadian O (eds): Wallhäussers Praxis der Sterilisation, Desinfektion, Antiseptik und Konservierung. Qualitätssicherung der Hygiene in Industrie, Pharmazie und Medizin. Stuttgart, Thieme, 2008, pp 789–793.
  25. Broxton P, Woodcock PM, Heatley F, Gilbert P: Interaction of some polyhexamethylene biguanides and membrane phospholipids in Escherichia coli. J Appl Bacteriol 1984;57:115–124.
  26. Gilbert P, Pemberton D, Wilkinson DE: Barrier properties of gram-negative cell envelope towards high molecular weight polyhexamethylene biguanides. J Appl Bacteriol 1990;69:585–592.
  27. Gilbert P, Pemberton D, Wilkinson DE: Synergism within polyhexamethylene biguanide biocide formulations. J Appl Bacteriol 1990;69:593–598.
  28. 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;54:111–115.
  29. Allen MJ, White GF, Morby AP: The response of Escherichia coli to exposure to the biocide polyhexamethylene biguanide. Microbiology 2006;152:989–1000.
  30. Glukhov E, Stark M, Burrows LL, Deber CM: Basis for selectivity of cationic antimicrobial peptides for bacterial versus mammalian membranes. J Biol Chem 2005;280:33960–33967.
  31. Singer SJ, Nicolson GL: The fluid mosaic model of the structure of cell membranes. Science 1972;175:720–731.
  32. Zhu S: Evidence for myxobacterial origin of eukaryotic defensins. Immunogenetics 2007;59:949–954.
  33. Smith JG, Nemerow GR: Mechanism of adenovirus neutralization by Human alpha-defensins. Cell Host Microbe 2008;3:11–19.
  34. Taylor K, Clarke DJ, McCullough B, Chin W, Seo E, Yang D, Oppenheim J, Uhrin D, Govan JR, Campopiano DJ, MacMillan D, Barran P, Dorin JR: Analysis and separation of residues important for the chemoattractant and antimicrobial activities of beta-defensin 3. J Biol Chem 2008;283:6631–6639.
  35. Krishnakumari V, Nagaraj R: Interaction of antibacterial peptides spanning the carboxy-terminal region of human beta-defensins 1–3 with phospholipids at the air-water interface and inner membrane of E. coli. Peptides 2008;29:7–14.
  36. Vylkova S, Sun JN, Edgerton M: The role of released ATP in killing Candida albicans and other extracellular microbial pathogens by cationic peptides. Purinergic Signal 2007;3:91–97.
  37. Sugiarto H, Yu PL: Mechanisms of action of ostrich beta-defensins against Escherichia coli. FEMS Microbiol Lett 2007;270:195–200.
  38. Morgera F, Antcheva N, Pacor S, Quaroni L, Berti F, Vaccari L, Tossi A: Structuring and interactions of human beta-defensins 2 and 3 with model membranes. J Pept Sci 2008;14:518–523.
  39. Donlan RM: Biofilms: microbial life on surfaces. Emerg Infect Dis 2002;8:881–890.
  40. Gjødsbøl K, Christensen JJ, Karlsmark T, Jørgensen B, Klein BM, Krogfelt KA: Multiple bacterial species reside in chronic wounds: a longitudinal study. Int Wound J 2006;1:1–2.
  41. Bjarnsholt T, Kirketerp-Møller K, Jensen PØ, Madsen KG, Phipps R, Krogfelt K, Høiby N, Givskov M: Why chronic wounds will not heal: a novel hypothesis. Wound Repair Regen 2008;16:2–10.

    External Resources

  42. Seipp HM, Hofmann S, Hack A, Skowronsky A, Hauri A: Efficacy of various wound irrigation solutions against biofilms. ZfW 2005;4:160–164.
  43. Blackburn RS, Harvey A, Kettle LL, Payne JD, Russell SJ: Sorption of poly(hexamethylene biguanide) on cellulose: mechanism of binding and molecular recognition. Langmuir 2006;22:5636–5644.
  44. Kusnetsov JM, Tulkki AI, Ahonen HE, Martikainen PJ: Efficacy of tree prevention strategies against Legionella in cooling water systems. J Appl Microbiol 1997;82:763–768.
  45. Perez R, Davis SC, Kaehn K: Wirkung verschiedener Wundspüllösungen auf MRSA-Biofilme in Wunden im Tiermodel. WundManagement 2010,4:44–48.
  46. Elsztein C, de Menezes JAS, de Morais MA Jr: Polyhexamethyl biguanide can eliminate contaminant yeasts from fuel-ethanol fermentation process. J Ind Microbiol Biotechnol 2008;35:967–973.
  47. Messick CR, Pendland SL, Moshirfar M, Fiscella RG, Losnedahl KJ, Schriever CA, Schreckenberger PC: In-vitro activity of polyhexamethylene biguanide (PHMB) against fungal isolates associated with infective keratitis. J Antimicrob Chemother 1999;44:297–298.
  48. Liu N, Khong D, Chung SK, Hwang DG: In-vitro susceptibility of ocular bacterial and fungal pathogens to polyhexamethylene biguanide. Invest Ophthamol Vis Sci 1996;37:4058.

    External Resources

  49. Larkin DFP, Kilvington S, Dart JKG: Treatment of Acanthamoeba keratitis with polyhexamethylene biguanide. J Ophthalmol 1992;99:185–191.
  50. Donoso R, Mura JJ, Lopez M: Acanthamoeba keratitis treated with propamidine and polyhexamethylene biguanide (PHMB). Rev Med Chil 2002;130:396–401.
  51. Narasimhan S, Madhavan HN, Therese LK: Development and application of an in vitro susceptibility test for Acanthamoeba species isolated from keratitis to polyhexamethylene biguanide and chlorhexidine. Cornea 2002;21:203–205.

    External Resources

  52. 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;59:438–445.
  53. Andriessen AE, Eberlein T: Assessment of a wound cleansing solution in the treatment of problem wounds. Wounds 2008;20:171–175.
  54. Möller A, Kaehn K, Nolte A: Erfahrungen mit dem Einsatz polyhexanidhaltiger Wundprodukte bei der Versorgung chronischer Wunden – Ergebnisse einer systematischen retrospektiven Untersuchung an 953 Patienten. WundManagement 2008;3:112–117.
  55. Cazzaniga A, Serralta V, Davis S, Orr R, Eaglestein W, Mertz PM: The effect of an antimicrobial gauze dressing impregnated with 0.2 percent polyhexamethylene biguanides as a barrier to prevent Pseudomonas aeruginosa wound invasion. Wounds 2002;14:169–176.
  56. United States Environmental Protection Agency: Reregistration eligibility decision of PHMB. EPA739-R-05-003, September 2005.
  57. 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 re-growth. J Clin Periodontol 2002;98:392–399.

    External Resources

  58. Brecx M, Decker EM, Freitag HP, Maier G, von Ohle C: The effect of polihexanide on dental biofilm formation in vivo. J Dent Res 2008;87:0528.
  59. Christiansen R, Palmork KH: Distribution and elimination of [14C] in saithe (Pollachius virens L.) after application of a single dose of [14C] polyhexamethylene hydrochloridbiguanide. Bull Environ Contam Toxicol 1996;36:121–128.

    External Resources

  60. Zöllner H, Kramer A, Youssef P, Youssef U, Adrian V: Preliminary investigations on the biodegradability of selected microbicidal agents. Hyg Med 1995;20:401–407.
  61. O’Malley LP, Collins AN, White GF: Biodegradability of end-groups of the biocide polyhexamethylene biguanide (PHMB) assessed using model compounds. J Ind Microbiol Biotechnol 2006;33:677–684.
  62. O’Malley LP, Shaw CH, Collins AN: Microbial degradation of the biocide polyhexamethylene biguanide: isolation and characterization of enrichment consortia and determination of degradation by measurement of stable isotope incorporation into DNA. J Appl Microbiol 2007;103:1158–1169.
  63. Kawai F: Sphingomonads involved in the biodegradation of xenobiotic compounds. J Ind Microbiol Biotechnol 1999;23:400–407.
  64. Hiraishi T, Kajiyama M, Yamoto I, Doi Y: Enzymatic hydrolysis of alpha- and beta-oligo(L-aspartic acid) by poly(aspartic acid) hydrolases-1 and 2 from Sphingomonas sp. KT-1. Macromol Biosci 2004;4:330–339.
  65. Vacca DJ, Bleam WF, Hickey WJ: Isolation of soil bacteria adapted to degrade humic acid-sorbed phenanthrene. Appl Environ Microbiol 2005;71:3797–3805.
  66. Mishima Y, Momma K, Hashimoto W, Mikami B, Murata K: Super-channel in bacteria: function and structure of the macromolecule import system mediated by a pit-dependent ABC transporter. FEMS Microbiol Lett 2001;204:215–221.