Skip to main content
Log in

The microbiome and its relevance in complex wounds

  • Review
  • Published:
European Journal of Dermatology

Abstract

Chronic wounds include arterial, venous, diabetic and pressure ulcers. The term “chronic wound” defines wounds that have not healed within three months. The possible causes that transform a simple wound into a chronic one are the object of study, and research has focused on infection as one of the crucial factors in producing and maintaining chronic wounds. In fact, 60% of chronic wounds are colonized by bacteria living in a biofilm. A biofilm is a complex aggregation of microorganisms characterized by the secretion of an adhesive and protective matrix. The two most common biofilm generators are Staphylococcus aureus and Pseudomonas aeruginosa. Several conditions constitute risk factors for the formation of biofilms, such as diabetes mellitus, venous insufficiency, malnutrition, cancer, oedema, and repetitive trauma. There are no standard diagnostic tests to determine the presence of biofilms, but there are several clinical indications which can help, and performing a tissue biopsy is better than a swab. Wound bed preparation is a crucial part of biofilm treatment and surgical or conservative sharp wound debridement are the preferred treatments that are effective in removing or reducing biofilms. We report three cases of complex wounds and their treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Zhao G, Usui ML, Lippman SI, et al. Biofilms and inflammation in chronic wounds. Adv Wound Care (New Rochelle) 2013; 2: 389–99.

    Article  Google Scholar 

  2. James GA, Swogger E, Wolcott R, et al. Biofilms in chronic wounds. Wound Repair Regen 2008; 16: 37–44.

    Article  PubMed  Google Scholar 

  3. Bianchi T, Wolcott RD, Peghetti A, et al. Recommendations for the management of biofilm: a consensus document. J Wound Care 2016; 25: 305–17.

    Article  CAS  PubMed  Google Scholar 

  4. Goslen JB. Autoimmune ulceration of the leg. Clin Dermatol 1990; 8: 92–117.

    Article  CAS  PubMed  Google Scholar 

  5. Ammons MC, Morrissey K, Tripet BP, et al. Biochemical association of metabolic profile and microbiome in chronic pressure ulcer wounds. PLoS One 2015; 10: e0126735.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Marchesi JR, Ravel J. The vocabulary of microbiome research: a proposal. Microbiome 2015; 3: 31.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Peterson DA, Frank DN, Pace NR, Gordon JI. Metagenomic approaches for defining the pathogenesis of inflammatory bowel diseases. Cell Host Microbe 2008; 3: 417–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Clinton A, Carter T. Chronic wound biofilms: pathogenesis and potential therapies. Lab Med 2015; 46: 277–84.

    Article  PubMed  Google Scholar 

  9. Lewis Sauer K, Camper A, Ehrlich G, Costerton J, Davies D. Pseudomonas aeruginosa displays multiple phenotypes during development as a biofilm. J Bacteriol 2002; 184: 1140–54.

    Article  Google Scholar 

  10. Lewis K. Multidrug tolerance of biofilms and persister cells. Curr Top Microbiol Immunol 2008; 322: 107–13.

    CAS  PubMed  Google Scholar 

  11. Chehoud C, Rafail S, Tyldsley AS, Seykora JT, Lambris JD, Grice E. Complement modulates the cutaneous microbiome and inflammatory milieu. Proc Natl Acad Sci USA 2013; 110: 15061–6.

    Article  PubMed  Google Scholar 

  12. Smith K, Collier A, Townsend EM, et al. One step closer to understanding the role of bacteria in diabetic foot ulcers: characterising the microbiome of ulcers. BMC Microbiol 2016; 16: 54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Lavigne JP, Sotto A, Dunyach-Remy C, Lipsky BA. New molecular techniques to study the skin microbiota of diabetic foot ulcers. Adv Wound Care (New Rochelle) 2015; 4: 38–49.

    Article  Google Scholar 

  14. Sanchez CJ Jr., Mende K, Beckius ML, et al. Biofilm formation by clinical isolates and the implications in chronic infections. BMC Infect Dis 2013; 13: 47.

    Article  PubMed  PubMed Central  Google Scholar 

  15. Forlee M. What is the diabetic foot? The rising prevalence of diabetes worldwide will mean an increasing prevalence of complications such as those of the extremities. CME 2011; 29: 4–8.

    Google Scholar 

  16. Høiby N, Bjarnsholt T, Moser C, et al. ESCMID guideline for the diagnosis and treatment of biofilm infection 2014. Clin Microbiol Infect 2015; 21: S1–25.

    Article  PubMed  Google Scholar 

  17. 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; 3: 225–31.

    Article  PubMed  Google Scholar 

  18. Redel H, Gao Z, Li H, et al. Quantitation and composition of cutaneous microbiota in diabetic and nondiabetic men. J Infect Dis 2013; 207: 1105–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Wolcott RD, Hanson JD, Rees EJ, et al. Analysis of the chronic wound microbiota of 2,963 patients by 16S rDNA pyrosequencing. Wound Repair Regen 2014; 24: 163–74.

    Article  Google Scholar 

  20. Kalan L, Loesche M, Hodkinson BP, et al. Redefining the chronic-wound microbiome: fungal communities are prevalent, dynamic and associated with delayed healing. MBio 2016; 7: e01058–1116.

    PubMed  PubMed Central  Google Scholar 

  21. Høiby N, Bjarnsholt T, Moser C, et al. ESCMID guideline for the diagnosis and treatment of biofilm infections 2014. Clin Microbiol Infect 2015; 1: S1–25.

    Article  Google Scholar 

  22. Martin JM, Zenilman JM, Lazarus GS. Molecular microbiology: new dimensions for cutaneous biology and wound healing. J Invest Dermatol 2010; 130: 3848.

    Google Scholar 

  23. Ren D, Madsen JS, Sørensen SJ, Burmølle M. High prevalence of biofilm synergy among 20 bacterial soil isolates in cocultures indicates bacterial interspecific cooperation. ISME J 2015; 9: 81–9.

    Article  CAS  PubMed  Google Scholar 

  24. Seth A, Gehringer M, Hong J, Leung K, Galiano RD, Mustoe TA. Comparative analysis of 24 single species and polybacterial wound biofilms using a quantitative, in vivo, rabbit ear model. PLoS One 2012; 7: e42897.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Wolcott RD, Kennedy JP, Dowd SE. Regular debridement is the main tool for maintaining a healthy wound bed in most chronic wounds. J Wound Care 2009; 18: 54–6.

    Article  CAS  PubMed  Google Scholar 

  26. Wolcott RD, Rumbaugh KP, James G, et al. Biofilm maturity studies indicate sharp debridement opens a time-dependent therapeutic window. J Wound Care 2010; 19: 320–8.

    Article  CAS  PubMed  Google Scholar 

  27. Lipsky BA, Hoey C. Topical antimicrobial therapy for treating chronic wounds. Clin Infect Dis 2009;49: 1541–9.

    Article  PubMed  Google Scholar 

  28. Daeschlein G. Antimicrobial and antiseptic strategies in wound management. Int Wound J 2013; 10: 9–14.

    Article  PubMed  Google Scholar 

  29. Han G, Ceilley R. Chronic wound healing: a review of current management and treatments. Adv Ther 2017; 34: 599–610.

    Article  PubMed  PubMed Central  Google Scholar 

  30. Barnes S, Spencer M, Graham D, Johnson HB. Surgical wound irrigation: a call for evidence-based standardization of practice. Am J Infect Control 2014; 42: 525–9.

    Article  Google Scholar 

  31. Patel PP, Vasquez SA, Granick MS, Rhee ST. Topical antimicrobials in pediatric burn wound management. J Craniofac Surg 2008; 19: 913–22.

    Article  PubMed  Google Scholar 

  32. Burd A, Kwok CH, Hung SC, et al. A comparative study of the cytotoxicity of silver-based dressings in monolayer cell, tissue explant, and animal model. Wound Repair Regen 2007; 15: 94–104.

    Article  PubMed  Google Scholar 

  33. Rani GN, Budumuru R, Bandaru NR. Antimicrobial activity of honey with special reference to methicillin resistant Staphylococcus aureus (MRSA) and methicillin sensitive Staphylococcus aureus (MSSA). J Clin Diagn Res 2017; 11: DC05–8.

    PubMed  PubMed Central  Google Scholar 

  34. Othman AS. Antibacterial activity of bee and Yemeni Sidr honey against some pathogenic bacterial species. Int J Curr Microbiol App Sci 2014; 3: 1015–25.

    Google Scholar 

  35. Al-Waili N, Salom K, Al-Ghamdi AA. Honey for wound healing, ulcers, and burns: data supporting its use in clinical practice. Scientific World Journal 2011; 11: 766–87.

    Article  PubMed  Google Scholar 

  36. Benhanifia MB, Boukraâ L, Hammoudi SM, Sulaiman SA, Manivannan. Recent patents on topical application of honey in wound and burn management. Recent Pat Inflamm Allergy Drug Discov 2011; 5: 81–6.

    Article  CAS  PubMed  Google Scholar 

  37. Narayanan A, Nair MS, Karumathil DP, Baskaran SA, Venkitanarayanan K, Amalaradjou MA. Inactivation of acinetobacter baumannii biofilms on polystyrene, stainless steel, and 20 urinary catheters by octenidine dihydrochloride. Front Microbiol 2016; 7: 1–9.

    Article  CAS  Google Scholar 

  38. Amalaradjou MA, Venkitanarayanan K. Antibiofilm effect of octenidine hydrochloride on Staphylococcus aureus, MRSA and VRSA. Pathogens 2014; 3: 404–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 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.

    Article  CAS  PubMed  Google Scholar 

  40. 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.

    Article  CAS  PubMed  Google Scholar 

  41. Ikeda T, Ledwith A, Bamford CH, Hann RA. Interaction of a polymeric biguanide biocide with phospholipid membranes. Biochim Biophys Acta 1984; 769: 57–66.

    Article  CAS  PubMed  Google Scholar 

  42. Høiby N, Bjarnsholt T, Givskov M, Molin S, Ciofu O. Antibiotic resistance of bacterial biofilms. Int J Antimicrob Agents 2010; 35: 322–32.

    Article  CAS  PubMed  Google Scholar 

  43. Szomolay B, Klapper I, Dockery J, Stewart PS. Adaptive responses to antimicrobial agents in biofilms. Environ Microbiol 2005; 7: 1186–91.

    Article  CAS  PubMed  Google Scholar 

  44. Stewart PS, Costerton JW. Antibiotic resistance of bacteria in biofilms. Lancet 2001; 358: 135–8.

    Article  CAS  PubMed  Google Scholar 

  45. Hengzhuang W, Høiby N, Ciofu O. Pharmacokinetics and pharmacodynamics of antibiotics in biofilm infections of Pseudomonas aeruginosa in vitro and in vivo. Methods Mol Biol 2014; 1147: 239–54.

    Article  CAS  PubMed  Google Scholar 

  46. Tseng BS, Zhang W, Harrison JJ, et al. The extracellular matrix protects Pseudomonas aeruginosa biofilms by limiting the penetration of tobramycin. Environ Microbiol 2013; 15: 2865–78.

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Doroshenko N, Tseng BS, Howlin RP, et al. Extracellular DNA impedes the transport of vancomycin in Staphylococcus epidermidis biofilms preexposed to subinhibitory concentrations of vancomycin. Antimicrob Agents Chemother 2014; 58: 7273–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Donlan RM, Costerton JW. Biofilms: survival mechanisms of clinically relevant microorganisms. Clin Microbiol Rev 2002; 15: 167–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Martin JM, Zenilman JM, Lazarus GS. Molecular microbiology: new dimensions for cutaneous biology and wound healing. J Invest Dermatol 2010; 130: 38–48.

    Article  CAS  PubMed  Google Scholar 

  50. Hentzer M, Wu H, Andersen JB, et al. Attenuation of Pseudomonas aeruginosa virulence by quorum sensing inhibitors. EMBO J 2003; 22: 3803–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Grandclément C, Tannières M, Moréra S, Dessaux Y, Faure D. Quorum quenching: role in nature and applied developments. FEMS Microbiol Rev 2016; 40: 86–116.

    Article  CAS  PubMed  Google Scholar 

  52. Van Delden C, Koehler T, Brunner-Ferber F, et al. Azithromycin to prevent Pseudomonas aeruginosa ventilator-associated pneumonia by inhibition of quorum sensing: a randomized controlled trial. Intens Care Med 2012; 38: 1118–25.

    Article  CAS  Google Scholar 

  53. Gupta P, Chhibber S, Harjai K. Efficacy of purified lactonase and ciprofloxacin in preventing systemic spread of Pseudomonas aeruginosa in murine burn wound model. Burns 2015; 41: 153–62.

    Article  PubMed  Google Scholar 

  54. Hamblin MR. Antimicrobial photodynamic inactivation: a bright new technique to kill resistant microbes. Curr Opin Microbiol 2016; 33: 67–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. De Melo WC, Avci P, De Oliveira MN, et al. Photodynamic inactivation of biofilm: taking a lightly colored approach to stubborn infection. Expert Rev Anti Infect Ther 2013; 11: 669–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kato IT, Prates RA, Sabino CP, et al. Antimicrobial photodynamic inactivation inhibits 37 Candida albicans virulence factors and reduces in vivo pathogenicity. Antimicrob Agents Chemother 2013; 57: 445–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Christensen GJ, Brüggemann H. Bacterial skin commensals and their role as host guardians. Benef Microbes 2014; 5: 201–15.

    Article  CAS  PubMed  Google Scholar 

  58. Baquerizo Nole KL, Yim E, Keri JE. Probiotics and prebiotics in dermatology. J Am Acad Dermatol 2014; 71: 814–21.

    Article  PubMed  Google Scholar 

  59. Aroniadis OC, Brandt LJ, Greenberg A, et al. Long-term follow-up study of fecal microbiota transplantation for severe and/or complicated clostridium difficile infection: a multicenter Experience. J Clin Gastroenterol 2016; 50: 398–440.

    PubMed  Google Scholar 

  60. Forlee M. What is the diabetic foot? The rising prevalence of diabetes worldwide will mean an increasing prevalence of complications such as those of the extremities. CME 2011; 29: 4–8.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Lodovica Gariazzo.

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Drago, F., Gariazzo, L., Cioni, M. et al. The microbiome and its relevance in complex wounds. Eur J Dermatol 29, 6–13 (2019). https://doi.org/10.1684/ejd.2018.3486

Download citation

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1684/ejd.2018.3486

Key words

Navigation