Biofilms in wounds: A review of present knowledge

Journal of Wound Care

Volumn 23, Issue 11, 2014, Pages 570-582

  Cooper, R A ^a   Bjarnsholt, T ^b,c   Alhede, M ^b,c  

^a CARDIFF METROPOLITAN UNIVERSITY   (United Kingdom)

^b UNIVERSITY OF COPENHAGEN   (Denmark)

^c Mental Health Services CPH   (Denmark)

Author keywords

Anti biofilm strategies; Biofilm detection; EPS; Extracellular polymeric substances; Immune evasion; Wound chronicity

Indexed keywords

ANTIINFECTIVE AGENT;

ANTIBIOTIC RESISTANCE; BIOFILM; DRUG EFFECTS; HUMAN; MICROBIOLOGY; WOUND HEALING; WOUND INFECTION; WOUNDS AND INJURIES;

ANTI-BACTERIAL AGENTS; BIOFILMS; DRUG RESISTANCE, BACTERIAL; HUMANS; WOUND HEALING; WOUND INFECTION; WOUNDS AND INJURIES;

EID: 84911368031     PISSN: 09690700     EISSN: None     Source Type: Journal    
DOI: 10.12968/jowc.2014.23.11.570     Document Type: Article

References (139)

1. Costerton, J.W., Cheng, K.J., Geesey, G.G. et al. Bacterial biofilms in nature and disease. Ann Rev Microbiol 1987; 41: 435-464.
2. Davey, M.E., O'Toole, G.A. Microbial biofilms: from ecology to molecular genetics. Microbiol Mol Biol Rev 2000; 64: 4, 847-867.
3. Bjarnsholt, T., Alhede, M., Alhede, M. et al. The in vivo biofilm. Trends Microbiol 2013; 21: 9, 466-474
4. Stoodley, P., Sauer, K., Davies, D.G., Costerton, J.W. Biofilms as complex differentiated communities. Ann Rev Microbiol 2002; 56: 187-209.
5. Costerton, J.W., Lewandowski, Z., Caldwell, D.E. et al. Microbial biofilms. Ann Rev Microbiol 1995; 49: 711-745.
6. Wingender, J., Strathmann, M. Rode, A., et al. Isolation and biochemical characterization of extracellular polymeric substances from Pseudomonas aeruginosa. Methods Enzymol 2001; 336: 302-314.
7. Whitchurch, C.B., Tolker-Nielsen, T., Ragas, P.C. et al. Extracellular DNA required for bacterial biofilm formation. Science 2002; 295: 5559,1487.
8. Costerton, W., Veeh, R., Shirtliff, M., et al. The application of biofilm science to the study and control of chronic bacterial infections. J Clin Invest 2003; 112: 10, 1466-1477.
9. Alhede, M., Kragh, K.N., Qvortrup, K. et al. Phenotypes of non-attached Pseudomonas aeruginosa aggregates resemble surface attached biofilm. PLoS One 2011; 6: 11, e27943.
10. Driffield, K., Miller, K., Bostock, J.M. et al. Increased mutability of Pseudomonas aeruginosa in biofilms. J Antimicrob Chemother 2008; 61: 5, 1053-1056.
11. Tyerman, J.G., Ponciano, J.M., Joyce, P., et al. The evolution of antibiotic susceptibility and resistance during the formation of Escherichia coli biofilms in the absence of antibiotics. BMC Evol Biol 2013; 13: 22.
12. Conibear, T.C., Collins, S.L., Webb, J.S. Role of mutation in Pseudomonas aeruginosa biofilm development. PLoS One 2009; 4: 7, e6289.
13. Bagge, N., Ciofu, O., Skovgaard, L.T., Holby, N. Rapid development in vitro and in vivo of resistance to ceftazidime in biofilm-growing Pseudomonas aeruginosa due to chromosomal beta-lactamase. APMIS 2000; 108: 9, 589-600.
14. De Kievit, T.R., Parkins, M.D., Gillis, R.J. et al. Multidrug efflux pumps: expression patterns and contribution to antibiotic resistance in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 2001; 45: 6, 1761-1770.
15. Zhang, L., Mah, T.F. Involvement of a novel efflux system in biofilm-specific resistance to antibiotics. J Bacteriol 2008; 190: 13, 4447-4452.
16. Soto, S.M. Role of efflux pumps in the antibiotic resistance of bacteria embedded in a biofilm. Virulence 2013; 4: 3, 223-229.
17. Pamp, S.J., Gjermansen, M., Johansen,H.K., Tolker-Nielsen, T. Tolerance to the antimicrobial peptide colistin in Pseudomonas aeruginosa biofilms is linked to metabolically active cells, and depends on the pmr and mexAB-oprM genes. Mol Microbiol 2008; 68: 1, 223-240.
18. Chiang, W.C., Pamp, S.J., Nilsson, M. et al. The metabolically active subpopulation in Pseudomonas aeruginosa biofilms survives exposure to membrane-targeting antimicrobials via distinct molecular mechanisms. FEMS Immunol Med Microbiol 2012; 65: 2, 245-256.
19. Ito, A., Taniuchi, A., May, T. et al. Increased antibiotic resistance of Escherichia coli in mature biofilms. Appl Environ Microbiol 2009; 75: 12, 4093-4100.
20. Bagge, N., Ciofu, O. Hentzer, M. et al. Constitutive high expression of chromosomal beta-lactamase in Pseudomonas aeruginosa caused by a new insertion sequence (IS1669) located in ampD. Antimicrob Agents Chemother 2002; 46: 11, 3406-3411.
21. Bagge, N., Hentzer, M., Andersen, J. B. et al. Dynamics and spatial distribution of beta-lactamase expression in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 2004; 48: 4, 1168-1174.
22. Hengzhuang, W., Ciofu, O., Yang, L. et al. High beta-lactamase levels change the pharmacodynamics of beta-lactam antibiotics in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 2013; 57: 1, 196-204.
23. Hengzhuang, W., Wu, H., Ciofu, O. et al. In vivo pharmacokinetics/ pharmacodynamics of colistin and imipenem in Pseudomonas aeruginosa biofilm infection. Antimicrob Agents Chemother 2012; 56: 5, 2683-2690.
24. Hengzhuang, W., Wu,H., Ciofu, O. et al. Pharmacokinetics/ pharmacodynamics of colistin and imipenem on mucoid and nonmucoid Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 2011; 55: 9, 4469-4474.
25. Hentzer, M., Teitzel, G.M., Balzer, G.J. et al. Alginate overproduction affects Pseudomonas aeruginosa biofilm structure and function. J Bacteriol 2001; 183: 18, 5395-5401.
26. Mah, T.F., Pitts, B., Pellock, B. et al. A genetic basis for Pseudomonas aeruginosa biofilm antibiotic resistance. Nature 2003; 426: 6964, 306-310.
27. Billings, N., Millan, M., Caldara, M. et al. The extracellular matrix Component Psl provides fast-acting antibiotic defense in Pseudomonas aeruginosa biofilms. PLoS Pathog 2013; 9: 8, e1003526.
28. Allesen-Holm, M., Barken, K.B., Yang, L. et al. A characterization of DNA release in Pseudomonas aeruginosa cultures and biofilms. Mol. Microbiol 2006; 59: 4, 1114-1128.
29. Walker, T.S., Tomlin, K.L., Worthen, G.S. et al. Enhanced Pseudomonas aeruginosa biofilm development mediated by human neutrophils. Infect. Immun. 2005; 73: 6, 3693-3701.
30. Chiang, W.C., Nilsson, M., Jensen, P.O. et al. Extracellular DNA shields against aminoglycosides in Pseudomonas aeruginosa biofilms. Antimicrob Agents Chemother 2013; 57: 5, 2352-2361.
31. Mulcahy, H., Charron- Mazenod, L., Lewenza, S. Extracellular DNA chelates cations and induces antibiotic resistance in Pseudomonas aeruginosa biofilms. PLoS Pathog 2008; 4: 11, e1000213.
32. Purdy Drew, K.R., Sanders, L.K., Culumber, Z.W. et al. Cationic amphiphiles increase activity of aminoglycoside antibiotic tobramycin in the presence of airway polyelectrolytes. J Am Chem Soc 2009; 131: 2, 486-493.
33. Evans, D.J., Brown, M.R., Allison, D.G. et al. Susceptibility of bacterial biofilms to tobramycin: role of specific growth rate and phase in the division cycle. J Antimicrob Chemother 1990; 25: 4, 585-591.
34. Hentzer, M., Eberl, L., Givskov, M. Transcriptome analysis of Pseudomonas aeruginosa biofilm development: anaerobic respiration and iron limitation. Biofilms 2005; 2: 1, 37-61.
35. Anderson, G.G., O'Toole, G.A. Innate and induced resistance mechanisms of bacterial biofilms. Curr Top Microbiol Immunol 2008; 322: 85-105.
36. Kuhl, M., Rickelt, L.F., Thar, R. Combined imaging of bacteria and oxygen in biofilms. Appl Environ Microbiol 2007; 73: 19, 6289-6295.
37. Alhede, M., Bjarnsholt, T. Jensen, P.O. et al. Pseudomonas aeruginosa recognizes and responds aggressively to the presence of polymorphonuclear leukocytes. Microbiology 2009; 155: 3500-3508.
38. Kharazmi, A. Mechanisms involved in the evasion of the host defence by Pseudomonas aeruginosa. Immunol Lett 1991; 30: 2, 201-205.
39. Kharazmi, A., Doring, G., Hoiby, N., Valerius, N.H. Interaction of Pseudomonas aeruginosa alkaline protease and elastase with human polymorphonuclear leukocytes in vitro. Infect Immun 1984; 43: 1, 161-165.
40. Pedersen, B.K., Kharazmi, A. Inhibition of human natural killer cell activity by Pseudomonas aeruginosa alkaline protease and elastase. Infect Immun 1987; 55: 4, 986-989.
41. Theander, T.G., Kharazmi, A., Pedersen, B.K. et al. Inhibition of human lymphocyte proliferation and cleavage of interleukin-2 by Pseudomonas aeruginosa proteases. Infect. Immun. 1988; 56: 7, 1673-1677.
42. Doring, G., Goldstein, W., Botzenhart, K. et al. Elastase from polymorphonuclear leucocytes: a regulatory enzyme in immune complex disease. Clin Exp Immunol 1986; 64: 3, 597-605.
43. Ogston A. Ueber abscesse. Archiv f Kin Chir 1880; 25: 599. Reproduced in: Macdonald, A., Smith, G. (eds) The staphylococci. Proceedings of the Alexander Ogston Centennial Conference. Aberdeen University Press, 1981.
44. Bigger, J.W. Treatment of staphylococcal infections with penicillin by intermittent sterilization. Lancet 1944; 244: 6320, 497-500.
45. Gristina, A.G., Price, J.L., Hobgood, C.D., et al. Bacterial colonisation of percutaneous sutures. Surgery 1985; 98: 1, 12-19.
46. Donlan, R.M. Biofilms and device-associated infections. Emerg Infect Dis 2001; 7: 2, 277-281.
47. Serralta, V.W., Harrison-Balestra, C., Cazzaniga, A.L., et al. Lifestyles of bacteria in wounds: presence of biofilms? Wounds 2001; 13: 1, 29-34.
48. Akiyama, H., Torigoe, R., Arata, J. Interaction of Staphylococcus aureus cells and silk thread in vitro and in mouse skin. J Dermatol Sci 1993; 6: 3, 247-257.
49. Akiyama, H., Kanzaki, H., Abe, Y., et al. Staphylococcus aureus infection on experimental croton oil-inflammed skin. J Dermatol Sci 1994; 8: 1, 1-10
50. Akiyama, H., Kanzaki, H., Tada, J., et al. Staphylococcus aureus infection on cut wounds in the mouse skin: experimental staphylococcal botryomycosis. J Dermatol Sci 1996; 11; 3, 234-238.
51. Akiyama, H., Huh, W.K., Yamasaki, O., et al. Confocal laser scanning microscopic observation of glycocalyx by Staphylococcus aureus in mouse skin: does S. aureus generally produce a biofilm on damaged skin? Br J Dermatol 2002;147: 5, 879-885.
52. Harrison-Balestra, C., Cazzaniga, A.L., Davis, S., Mertz, P.M. A wound-isolated Pseudomonas aeruginosa grows a biofilm in vitro within 10 hours and is visualised by light microscopy. Dermatol Surg 2003; 29: 6, 631-635.
53. Bjarnsholt, T., Kirketerp-Moller, K., Jensen, P.O., et al. Why chronic wounds will not heal: a novel hypothesis. Wound Repair Regen 2008; 16: 1, 2-10
54. James, G.A., Swogger, E., Wolcott, R., et al. Biofilms in chronic wounds. Wound Repair Regen 2008; 16: 1, 37-44.
55. Thomsen, T.R., Aasholm, M.S., Rudkjobing, V.B. et al. The bacteriology of chronic venous leg ulcer examined by culture-independent molecular methods. Wound Repair Regen 2010; 18:1, 38-49.
56. Dowd, S.E., Sun, Y., Secor, P.R. et al. Survey of bacterial diversity in chronic wounds using pyrosequencing, DGGE, and full ribosome shotgun sequencing. BMC Microbiol 2008; 8: 43.
57. Gjodsbol, K., Christensen, J.J., Karlsmark, T., et al. Multiple bacterial species reside in chronic wounds: a longitudinal study. Int Wound J 2006; 3: 3, 225-231.
58. Kirketerp-Moller, K., Jensen, P.O., Fazli, M., et al. Distribution, organization, and ecology of bacteria in chronic wounds. J Clin Microbiol 2008; 46: 8, 2717-2722.
59. Fazli, M., Bjarnsholt, T., Kirketerp-Moller, K., et al. Non-random distribution of Pseudomonas aeruginosa and Staphylococcus aureus in chronic wounds. J Clin Microbiol 2009; 47: 12, 4084-4089.
60. Malic, S., Hill, K.E., Hayes, A., et al. Detection and identification of specific bacteria in wound biofilms using peptide nucleic acid fluorescence in situ hybridization (PNA FISH). Microbiol 2009; 155: 2603-2611.
61. Kennedy, P., Brammah, S., Wills, W. Burns, biofilm and a new appraisal of burns sepsis. Burns 2010; 36: 1, 49-56.
62. Neut, D., Tijdens-Creusen, E.J.A., Bulstra, S.K., et al. Biofilms in chronic diabetic foot ulcers-a study of 2 cases. Acta Orthopaedica 2011; 82: 3, 383-385.
63. Fromantin, I., Seyer, D., Watson, S., et al. Bacterial floras and biofilms of malignant wounds associated with breast cancers. J Clin Microbiol 2013; 51: 10, 3368-3373.
64. Alhede, M., Er, Ö., Eickhardt, S. et al. Bacterial biofilm formation and treatment in soft tissue fillers. Pathog Dis 2014; 70: 3, 339-346.
65. Rudkjobing, V.B., Thomsen, T.R., Alhede, M., et al. The microorganisms in chronically infected end-stage and non-end-stage cystic fibrosis patients. FEMS Immunol Med Microbiol 2012; 65: 2, 236-44.
66. Burmolle, M., Thomsen, T.R., Fazli, M., et al. Biofilms in chronic infections - a matter of opportunity - monospecies biofilms in multispecies infections. FEMS Immunol Med Microbiol 2010; 59: 3, 324-336.
67. Bjarnsholt, T., Jensen, P.O., Fiandaca, M.J., et al. Pseudomonas aeruginosa biofilms in the respiratory tract of cystic fibrosis patients. Pediatr Pulmonol 2009; 44: 6, 547-558.
68. Bjarnsholt, T. The role of bacterial biofilms in chronic infections. APMIS Suppl 2013; 136: 1-51.
69. Hogsberg, T., Bjarnsholt, T., Thomsen, J.S., Kirketerp-Moller, K. Success rate of split-thickness skin grafting of chronic venous leg ulcers depends on the presence of Pseudomonas aeruginosa: A Retrospective Study. PLoS One 2011; 6: 5, e20492.
70. 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: 3, 387-391.
71. Davis, S.C., Ricotti, C., Cazzaniga, A., et al. Microscopic and physiologic evidence for biofilm-associated wound colonization in vivo. Wound Repair Regen 2008; 16: 23-29.
72. Stewart, P.S., Costerton, J.W. Antibiotic resistance of bacteria in biofilms. Lancet 2001; 358: 9276, 135-138.
73. Hall-Stoodley, L., Stoodley, P., Kathju, S., et al. Towards diagnostic guidelines for biofilm-associated infections. FEMS Immunol Med Microbiol 2012; 65: 2,127-145.
74. Weinberg, E.D. Suppression of bacterial biofilms by iron limitation. Med Hypotheses 2004; 63: 5, 863-865.
75. Tapininen, T., Sormunen, R., Kaijalainen, T., et al. Ultrastructure of Streptococcus pneumoniae after exposure to xylitol. J Antimicrob Chemother 2004; 54: 1, 225-228.
76. Ammons, M.C., Ward, L.S., Fisher, S.T., et al. In vitro susceptibility of established biofilms composed of a clinical wound isolate of Pseudomonas aeruginosa treated with lactoferrin and xyltiol. Int J Antimicrob Agents 2009; 33: 3, 230-236.
77. Lerrer, B., Zinger-Yosovich, K.D., Avrahami, B., Gilboa-Garber, N. Honey and royal jelly, like human milk, abrogate lectin-dependent infection preceding Pseudomonas aeruginosa adhesion. ISME J 2007; 1: 2, 149-155.
78. Roberts, A.E., Maddocks, S.E., Cooper, R.A. Manuka honey is bactericidal against Pseudomonas aeruginosa and results in differential expression of oprF and algD. Microbiology 2012; 158: 3005-3013.
79. Maddocks, S.E., Lopez, M.S., Rowlands, R.S., Cooper, R.A. Manuka honey inhibits the development of Streptococcus pyogenes biofilms and causes reduced expression of two fibronectin binding proteins. Microbiology 2012; 158: 781-790.
80. Shapiro, J.A. Thinking about bacterial populations as multicellular organisms. Ann Rev Microbiol 1998; 52: 81-104.
81. Fuqua, W.C., Winans, S.C. Greenberg, E.P. Quorum sensing in bacteria: the LuxR-LuxI family of cell density-responsive transcriptional regulators. J Bacteriol 1994; 176: 2, 269-275.
82. Waters, C.M., Bassler, B.L. Quorum sensing: cell-to-cell communication in bacteria. Annu Rev Cell Dev Biol 2005; 21: 319-346.
83. Hentzer, M., Wu, H., Andersen, J.B. et al. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 2003; 22: 3803-3815.
84. Wu, H., Song, Z., Hentzer, M. et al. Synthetic furanones inhibit quorum-sensing and enhance bacterial clearance in Pseudomonas aeruginosa lung infection in mice. J Antimicrob Chemother 2004; 53: 6, 1054-1061.
85. Jakobsen, T. H., Bragason, S. K., Phipps, R. K., et al. Food as a source for quorum sensing inhibitors: iberin from horseradish revealed as a quorum sensing inhibitor of Pseudomonas aeruginosa. Appl Environ Microbiol 2012; 78: 7, 2410-2421.
86. Jakobsen, T. H., van Gennip, M., Phipps, R. K. et al. Ajoene, a sulfur-rich molecule from garlic, inhibits genes controlled by quorum sensing. Antimicrob Agents Chemother 2012; 56: 5, 2314-2325.
87. Truchado, P., Lopez-Galvez, F., Gil, M.I., et al. Quorum sensing inhibitory and antimicrobial activities of honeys and the relationship with individual phenols. Food Chemistry 2009;115: 1337-1344.
88. Truchado, P., Gil-Izquierdo, A., Tomas-Barberan, F. et al. Inhibition by chestnut honey of N-Acetyl-L-homoserine lactones and biofilm formation in Erwinia carotovora, Yersinia entercolitica, and Aeromonas hydrophila. J Agric Food Chem 2009; 57: 11186-11193.
89. Wang, R, Starkey, M., Hazan, R., Rahme, L.G. Honey's ability to counter bacterial infections arises from both bactericidal compounds and QS inhibition. Frontiers Microbiol 2012; 3: 144.
90. Jenkins, R.E., Burton, N.F., Cooper, R.A. Proteomic and genomic analysis of methicillin-resistant Staphylococcus aureus (MRSA) exposed to manuka honey in vitro demonstrated down-regulation of virulence markers. J Antimicrob Chemother 2014; 69: 3, 603-615.
91. Nemoto, K., Hirota, K., Murakami, K., et al. Effect of varidase (streptodornase) on biofilm of Pseudomonas aeruginosa. Chemotherapy 2003; 49: 3, 121-125.
92. Chambers, L., Woodrow, S., Brown, A.P., et al. Degradation of extracellular matrix components by defined proteinases from the greenbottle larvae Lucilia sericata used for the clinical debridement of non-healing wounds. Br J Dermatol 2003; 148: 1, 14-23.
93. Cooper, R.A. Inhibition of biofilms by glucose oxidase, lactoperoxidase and guaiacol: the active antibacterial component in an enzyme alginogel. Int Wound J 2013; 10: 6, 630-637.
94. Merckoll, P., Jonassen, T.O., Vad, M.E., et al. Bacteria, biofilm and honey: A study of the effects of honey on 'planktonic' and biofilm-embedded wound bacteria. Scand J Infect Dis 2009; 41: 5, 341-347.
95. Alandejani, T., Marsan, J., Ferris, W., et al. Effectiveness of honey on Staphylococcus aureus and Pseudomonas aeruginosa biofilms. Otolarynology- Head Neck Surg 2009; 141: 1, 114-118.
96. Maddocks, S.E., Jenkins, R.E., Rowlands, R.S., et al. Manuka honey inhibits adhesion and invasion of medically important wound bacteria in vitro. Future Microbiol 2013; 8: 12, 1523-1536.
97. Cooper, R., Jenkins, L., Hooper, S. Inhibition of biofilms of Pseudomonas aeruginosa by Medihoney in vitro. J Wound Care 2014; 23: 3, 93-104.
98. Carmen, J.C., Nelson, J.L., Beckstead, B.L. et al. Ultrasonic-enhanced gentamicin transport through colony biofilms of Pseudomonas aeruginosa and Escherichia coli. J Infect Chemother 2004; 10: 4, 193-199.
99. Carmen, J.C., Roeder, B.L., Nelson, J.L. et al. Ultrasonically enhanced vancomycin activity against Staphylococcus epidermidis biofilms in vivo. J Biomater Appl 2004; 18: 4, 237-245.
100. Ensing, G.T., Neut, D., van Horn, J.R., et al. The combination of ultrasound with antibiotics released from bone cement decreases the viability of planktonic and biofilm bacteria: an in vitro study with clinical strains. J Antimicrob Chemother 2006; 58: 6, 1287-1290.
101. Pitt, W.G., McBride, M.O., Lunceford, J.K., et al. Ultrasonic enhancement of antibiotic action on gram-negative bacteria. Antimicrob Agents Chemother 1994; 38: 11, 2577-2582.
102. Rapoport, N., Smirnov, A.I., Timoshin, A., et al. Factors affecting the permeability of Pseudomonas aeruginosa cell walls toward lipophilic compounds: effects of ultrasound and cell age. Arch Biochem Biophys 1997; 344: 1, 114-124.
103. Rapoport, N., Smirnov, A.I., Pitt, W.G., et al. Bioreduction of Tempone and spin-labeled gentamicin by gram-negative bacteria: kinetics and effect of ultrasound. Arch Biochem Biophys 1999; 362: 2, 233-241.
104. Rediske, A.M., Hymas, W.C., Wilkinson,R., Pitt. W.G. Ultrasonic enhancement of antibiotic action on several species of bacteria. J Gen Appl Microbiol 1998; 44: 4, 283-288.
105. Rediske, A. M., Roeder, B.L., Brown, M.K., et al. Ultrasonic enhancement of antibiotic action on Escherichia coli biofilms: an in vivo model. Antimicrob Agents Chemother 1999; 43: 5, 1211-1214.
106. Qian, Z., Stoodley, P. Pitt, W.G. Effect of low-intensity ultrasound upon biofilm structure from confocal scanning laser microscopy observation. Biomaterials 1996; 17: 20, 1975-1980.
107. Liu, J., Lewis, T.N. Prausnitz, M.R. Non-invasive assessment and control of ultrasound-mediated membrane permeabilization. Pharm Res 1998; 15: 6, 918-924.
108. Runyan, C. M., Carmen, J.C., Beckstead, B.L., et al. Low-frequency ultrasound increases outer membrane permeability of Pseudomonas aeruginosa. J Gen Appl Microbiol 2006; 52: 5, 295-301.
109. Nikaido, H. Molecular basis of bacterial outer membrane permeability revisited. Microbiol Mol Biol Rev 2003; 67: 4, 593-656.
110. Pong, M., Umchid, S., Guarino, A. J. et al. In vitro ultrasound-mediated leakage from phospholipid vesicles. Ultrasonics 2006; 45: 133-145.
111. Nishikawa, T., Yoshida, A., Khanal, A. et al A study of the efficacy of ultrasonic waves in removing biofilms. Gerodontology 2010; 27: 3, 199-206.
112. Karau, M. J., Piper, K.E.,Steckelberg, J.M., et al. In vitro activity of the Quostic Wound Therapy System against planktonic and biofilm bacteria. Adv Skin Wound Care 2010; 23: 7, 316-320.
113. Tollefson, D. F., Bandyk, D.F., Kaebnick, H.W., et al. Surface biofilm disruption. Enhanced recovery of microorganisms from vascular prostheses. Arch Surg 1987; 122: 1, 38-43.
114. Pitt, W.G., Ross, S.A. Ultrasound increases the rate of bacterial cell growth. Biotechnol Prog 2003; 19: 3, 1038-1044.
115. Ramundo, J., Gray, M. Is ultrasonic mist therapy effective for debriding chronic wounds? J Wound, Ostomy, Continence Nurs 2008; 35: 6, 579-583.
116. Escandon, J., Vivas, A.C.,Perez, R., et al. A prospective pilot study of ultrasound therapy effectiveness in refractory venous leg ulcers. Int Wound J 2012; 9: 5, 570-578.
117. Vicenti, F.A., Laus, J.L., Costa Neto, J.M. et al. Effects of low-intensity pulsed ultrasound on wound healing in corneas of dogs following keratoplasty. Vet Ophthalmol 2003; 6: 3, 255-263.
118. Hess, C.L., Howard, M.A., Attinger, C.E. A review of mechanical adjuncts in wound healing: hydrotherapy, ultrasound, negative pressure therapy, hyperbaric oxygen, and electrostimulation. Ann Plast Surg 2003; 51: 2, 210-218.
119. Butcher, G., Pinnuck, L. Wound bed preparation: ultrasonic-assisted debridement. Br J Nurs 2013; 22: 6, S36, S38-43.
120. Soothill, J. Use of bacteriophages in the treatment of Pseudomonas aeruginosa infections. Expert Rev Anti Infect Ther 2013; 11: 9, 909-915.
121. Chhibber, S., Kaur, T., Kaur, S. Co-therapy using lytic bacteriophage and linezolid: effective treatment in eliminating methicillin-resistant Staphylococcus aureus (MRSA) from diabetic foot infections. PLoS One 2013; 8: 2, e56022.
122. Mendes, J.J., Leandro, C., Corte-Real, S., et al. Wound healing potential of topical bacteriophage therapy on diabetic cutaneous wounds. Wound Repair Regen 2013; 21: 4, 595-603
123. Rhoads, D.D, Wolcott, R.D., Wolcott, M.A., et al. Bacteriophage therapy of venous leg ulcers in humans: results of a phase I safety trial. J Wound Care 2009; 18: 6, 237-243.
124. Abedon, S.T. Bacteriophages and biofilms. In: Bailey W.C. (ed) Biofilms: formation, development and properties. Nova Science Publishers Inc, 2011.
125. Seth, A.K., Geringer, M.R., Nquyen, K.T., et al. Bacteriophage therapy foot Staphylococcus aureus biofilm-infected wounds: a new approach to chronic wound care. Plast Reconstr Surg 2013; 131: 2, 225-234.
126. Wolcott, R.D., Rhoads, D.D. A study of biofilm-based management of subjects with critical limb ischemia. J Wound Care 2008; 17: 4, 145-155.
127. Coenye, T., Nelis, H.J. In vitro and in vivo model systems to study microbial biofilm formation. J Microbiol Methods 2014; 83: 2, 89-109.
128. Sun, Y., Dowd, S.E., Smith, E., et al. In vitro multispecies Lubbock chronic wound biofilm model. Wound Repair Regen 2008; 16: 6, 805-813.
129. Werthén, M., Henriksson, L., Jensen, P.O., et al. An in vitro model of bacterial infections in wounds and other soft tissues. APMIS 2010; 118: 2, 156-164.
130. Charles, C.A., Ricotti, C.A., Davis, S.C., et al. Use of tissue-engineered skin to study in vitro biofilm development. Dermatol Surg 2009; 35: 9, 1334-1341.
131. Thorn, R.M. Nelson, S.M., Greenman, J. Use of a bioluminescent Pseudomonas aeruginosa strain within an in vitro microbiological system, as a model of wound infection, to assess the antimicrobial efficacy of wound dressings by monitoring light production. Antimicrob Agents Chemother 2007; 51: 9, 3217-3224.
132. Thorn, R.M., Greenman, J. A novel in vitro flat-bed perfusion biofilm model for determining the potential antimicrobial efficacy of topical wound dressings. J Appl Microbiol 2009; 107: 6, 2070-2079.
133. Lipp, C., Kirke, K., Agostinho, A., et al. Testing wound dressings using an in vitro wound model. J Wound Care 2010; 19: 6, 220-226.
134. Hill, K.E., Malic, S., McKee, R. et al. An in vitro model of chronic wound biofilms to test wound dressings and assess antimicrobial susceptibilities. J Antimicrob Chemother 2010; 65: 6, 1195-1206.
135. Nakagami, G, Sanada, H., Sugama, J., et al. Detection of Pseudomonas aeruginosa quorum sensing signals in an infected ischemic wound: an experimental study in rats. Wound Repair Regen 2008; 16: 1, 30-36.
136. Simonetti, O., Cirioni, O., Ghiselli, R., et al. RNAIII-inhibiting peptide enhances healing of wounds infected with methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 2008; 52: 6, 2205-2211.
137. Schierle, C.F., de la Garza, M., Mustoe, T.A., Galiano, R.D. Staphylococcal biofilms impair wound healing by delaying reepithelialisation in a murine cutaneous wound model. Wound Repair Regen 2009; 17: 3, 354-359.
138. Kanno, E., Toriyabe, S., Zhang, L., et al. Biofilm formation on rats skin wounds by Pseudomonas aeruginosa carrying green fluorescent protein gene. Exp Dermatol 2010; 19: 2, 154-156
139. Dowd, S.E., Wolcott, R.D., Sun, Y. et al. Polymicriobial nature of chronic diabetic foot ulcer biofilm infections determined using bacterial tag encoded FLX amplicon pyrosequencing (bTEFAP). PLoS One 2008; 3, 10, e3326.