Skip to main content
SpringerLink
Log in
Book cover

Targeting Biofilms in Translational Research, Device Development, and Industrial Sectors pp 11–27Cite as

Biofilm Infections in Orthopedic Surgery and Their Impact on Commercial Product Development

  • Chapter
  • First Online:

  • 304 Accesses

Abstract

The biofilm nature of bacterial infections on orthopedic implants imparts antibiotic tolerance, which means that these infections often cannot be successfully treated with systemic antibiotics alone. These infections must instead be treated surgically, which comes with high financial costs and patient morbidity. Because of this, much industrial research and new product development effort has focused on technologies to prevent infection by preventing biofilm formation on implants. Implant surface modification and local antibiotic delivery are primary areas of technology development. Antimicrobial-eluting orthopedic trauma implants have been commercialized and appear to be clinically effective but have not yet enjoyed widespread commercial success. The primary barriers to clinical development of infection-resistant implants in orthopedics are not technical, but commercial and regulatory. The large size and high cost of clinical trials in orthopedics, combined with the fragmented nature of the orthopedic implant market and indication-specific regulatory approvals, make it unlikely that the market for any single implant design can support the cost of clinical data required for approval. The regulatory pathway for any individual product design, typically a function of product risk profile, is a key factor determining clinical data requirements and therefore development costs. By accounting for these non-clinical challenges early in the technology development cycle it may be possible for industry, in partnership with clinicians and regulatory bodies, to bring forward anti-biofilm technologies for orthopedic surgery implants.

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

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. Hörlein, H. (1935). The chemotherapy of infectious diseases caused by Protozoa and Bacteria. Proceedings of the Royal Society of Medicine, XXIX(313).

    Google Scholar 

  2. Chain, E., Florey, H. W., Gardner, A. D., et al. (1940). Penicillin as a chemotherapeutic agent. The Lancet, 1940, 226–228.

    Article  Google Scholar 

  3. Foulis, M. A., & Barr, J. B. (1937). Prontosil album in puerperal sepsis. British Medical Journal, 27(1937), 445–446.

    Article  Google Scholar 

  4. Abraham, E. P., Chain, E., Fletcher, C. M., et al. (1941). Further observations on penicillin. The Lancet, 1941, 177–188.

    Article  Google Scholar 

  5. Barber, M. (1947). Staphylococcal infection due to penicillin-resistant strains. British Medical Journal, 2(4534), 863–865.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Alekshun, M. N., & Levy, S. B. (2007). Molecular mechanisms of antibacterial multidrug resistance. Cell, 128(6), 1037–1050.

    Article  CAS  PubMed  Google Scholar 

  7. Stoodley, P., Ehrlich, G. D., Sedghizadeh, P. P., et al. (2011). Orthopaedic biofilm infections. Current Orthopaedic Practice, 22(6), 558–563.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Nana, A., Nelson, S. B., & McLaren, A. (2016). What’s new in musculoskeletal infection: Update on biofilms. The Journal of Bone and Joint Surgery. American Volume, 98(14), 1226–1234.

    Article  PubMed  Google Scholar 

  9. Voigt, J., Mosier, M., & Darouiche, R. (2015). Systematic review and meta-analysis of randomized controlled trials of antibiotics and antiseptics for preventing infection in people receiving primary total hip and knee prostheses. Antimicrobial Agents and Chemotherapy, 59(11), 6696–6707.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Namba, R. S., Inacio, M. C., & Paxton, E. W. (2013). Risk factors associated with deep surgical site infections after primary total knee arthroplasty: An analysis of 56,216 knees. The Journal of Bone and Joint Surgery. American Volume, 95(9), 775–782.

    Article  PubMed  Google Scholar 

  11. Stall, A., Paryavi, E., Gupta, R., et al. (2013). Perioperative supplemental oxygen to reduce surgical site infection after open fixation of high-risk fractures: A randomized controlled pilot trial. Journal of Trauma and Acute Care Surgery, 75(4), 657–663.

    Article  CAS  PubMed  Google Scholar 

  12. Bosse, M. J., Murray, C. K., Carlini, A. R., et al. (2017). Assessment of severe extremity wound bioburden at the time of definitive wound closure or coverage: Correlation with subsequent postclosure deep wound infection (bioburden study). Journal of Orthopaedic Trauma, 31(Suppl 1), S3–S9.

    Article  PubMed  Google Scholar 

  13. Urish, K. L., Bullock, A. G., Kreger, A. M., et al. (2018). A multicenter study of irrigation and debridement in Total knee arthroplasty Periprosthetic joint infection: Treatment failure is high. The Journal of Arthroplasty, 33(4), 1154–1159.

    Article  PubMed  Google Scholar 

  14. Grammatopoulos, G., Bolduc, M. E., Atkins, B. L., et al. (2017). Functional outcome of debridement, antibiotics and implant retention in periprosthetic joint infection involving the hip: A case-control study. The Bone & Joint Journal, 99-B(5), 614–622.

    Article  CAS  Google Scholar 

  15. Haddad, F. S., Sukeik, M., & Alazzawi, S. (2015). Is single-stage revision according to a strict protocol effective in treatment of chronic knee arthroplasty infections? Clinical Orthopaedics and Related Research, 473(1), 8–14.

    Article  PubMed  Google Scholar 

  16. Cooper, H. J., & Della Valle, C. J. (2013). The two-stage standard in revision total hip replacement. The Bone & Joint Journal, 95-B(11 Suppl A), 84–87.

    Article  CAS  Google Scholar 

  17. Thakore, R. V., Greenberg, S. E., Shi, H., et al. (2015). Surgical site infection in orthopedic trauma: A case-control study evaluating risk factors and cost. Journal of Clinical Orthopaedics & Trauma, 6(4), 220–226.

    Article  Google Scholar 

  18. Stambough, J. B., Nam, D., Warren, D. K., et al. (2017). Decreased hospital costs and surgical site infection incidence with a universal decolonization protocol in primary total joint arthroplasty. The Journal of Arthroplasty, 32(3), 728–734.e1.

    Article  PubMed  Google Scholar 

  19. Horn, J., Stelzner, K., Rudel, T., et al. (2017). Inside job: Staphylococcus aureus host-pathogen interactions. International Journal of Medical Microbiology, S1438-4221(17), 30316–30318.

    Google Scholar 

  20. de Mesy Bentley, K. L., Trombetta, R., Nishitani, K., et al. (2017). Evidence of Staphylococcus Aureus deformation, proliferation, and migration in canaliculi of live cortical bone in murine models of osteomyelitis. Journal of Bone and Mineral Research, 32(5), 985–990.

    Article  CAS  PubMed  Google Scholar 

  21. Williams, D. L., & Costerton, J. W. (2012). Using biofilms as initial inocula in animal models of biofilm-related infections. Journal of Biomedical Materials Research. Part B, Applied Biomaterials, 100(4), 1163–1169.

    Article  CAS  PubMed  Google Scholar 

  22. Chiang, H. Y., Herwaldt, L. A., Blevins, A. E., et al. (2014). Effectiveness of local vancomycin powder to decrease surgical site infections: A meta-analysis. The Spine Journal, 14(3), 397–407.

    Article  PubMed  Google Scholar 

  23. Evaniew, N., Khan, M., Drew, B., et al. (2015). Intrawound vancomycin to prevent infections after spine surgery: A systematic review and meta-analysis. European Spine Journal, 24(3), 533–542.

    Article  PubMed  Google Scholar 

  24. Owen, M. T., Keener, E. M., Hyde, Z. B., et al. (2017). Intraoperative topical antibiotics for infection prophylaxis in pelvic and acetabular surgery. Journal of Orthopaedic Trauma, 31(11), 589–594.

    Article  PubMed  Google Scholar 

  25. Singh, K., Bauer, J. M., LaChaud, G. Y., et al. (2015). Surgical site infection in high-energy peri-articular tibia fractures with intra-wound vancomycin powder: A retrospective pilot study. Journal of Orthopaedics and Traumatology, 16(4), 287–291.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Firoozabadi, R., Miranda, S., & Tornetta, P., 3rd. (2017). Technique for placement of peri-implant antibiotics using antibiotic putty. Journal of Orthopaedic Trauma, 31(12), e442–e445.

    Article  PubMed  Google Scholar 

  27. Lawing, C. R., Lin, F. C., & Dahners, L. E. (2015). Local injection of aminoglycosides for prophylaxis against infection in open fractures. The Journal of Bone and Joint Surgery. American Volume, 97(22), 1844–1851.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Flierl, M. A., Culp, B. M., Okroj, K. T., et al. (2017). Poor outcomes of irrigation and debridement in acute periprosthetic joint infection with antibiotic-impregnated calcium sulfate beads. The Journal of Arthroplasty, 32(8), 2505–2507.

    Article  PubMed  Google Scholar 

  29. Boxma, H., Broekhuizen, T., Patka, P., et al. (1996). Randomised controlled trial of single-dose antibiotic prophylaxis in surgical treatment of closed fractures: The Dutch Trauma Trial. Lancet, 347(9009), 1133–1137.

    Article  CAS  PubMed  Google Scholar 

  30. Bratzler, D. W., Dellinger, E. P., Olsen, K. M., et al. (2013). Clinical practice guidelines for antimicrobial prophylaxis in surgery. American Journal of Health-System Pharmacy, 70(3), 195–283.

    Article  CAS  PubMed  Google Scholar 

  31. Schweizer, M., Perencevich, E., McDanel, J., et al. (2013). Effectiveness of a bundled intervention of decolonization and prophylaxis to decrease Gram positive surgical site infections after cardiac or orthopedic surgery: Systematic review and meta-analysis. BMJ, 346, f2743.

    Article  PubMed  PubMed Central  Google Scholar 

  32. Rasouli, M. R., Restrepo, C., Maltenfort, M. G., et al. (2014). Risk factors for surgical site infection following total joint arthroplasty. The Journal of Bone and Joint Surgery. American Volume, 96(18), e158.

    Article  PubMed  Google Scholar 

  33. Nelson, C. L., McLaren, A. C., McLaren, S. G., et al. (2005). Is aseptic loosening truly aseptic? Clinical Orthopaedics and Related Research, (437), 25–30.

    Google Scholar 

  34. Parvizi, J., Zmistowski, B., Berbari, E. F., et al. (2011). New definition for periprosthetic joint infection: From the Workgroup of the Musculoskeletal Infection Society. Clinical Orthopaedics and Related Research, 469(11), 2992–2994.

    Article  PubMed  PubMed Central  Google Scholar 

  35. Deirmengian, C., Kardos, K., Kilmartin, P., et al. (2015). The alpha-defensin test for periprosthetic joint infection responds to a wide spectrum of organisms. Clinical Orthopaedics and Related Research, 473(7), 2229–2235.

    Article  PubMed  PubMed Central  Google Scholar 

  36. Bonanzinga, T., Zahar, A., Dütsch, M., et al. (2017). How reliable is the alpha-defensin immunoassay test for diagnosing periprosthetic joint infection? A prospective study. Clinical Orthopaedics and Related Research, 475(2), 408–415.

    Article  PubMed  Google Scholar 

  37. Gehrke, T., Lausmann, C., Citak, M., et al. (2018). The accuracy of the alpha defensin lateral flow device for diagnosis of periprosthetic joint infection: Comparison with a gold standard. The Journal of Bone and Joint Surgery. American Volume, 100(1), 42–48.

    Article  PubMed  Google Scholar 

  38. Vincent, J. L., Brealey, D., Libert, N., et al. (2015). Rapid diagnosis of infection in the critically ill, a multicenter study of molecular detection in bloodstream infections, pneumonia, and sterile site infections. Critical Care Medicine, 43(11), 2283–2291.

    Article  CAS  PubMed  Google Scholar 

  39. Greenwood-Quaintance, K. E., Uhl, J. R., Hanssen, A. D., et al. (2014). Diagnosis of prosthetic joint infection by use of PCR-electrospray ionization mass spectrometry. Journal of Clinical Microbiology, 52(2), 642–649.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Rasouli, M. R., Harandi, A. A., Adeli, B., et al. (2012). Revision total knee arthroplasty: Infection should be ruled out in all cases. The Journal of Arthroplasty, 27(6), 1239–43.e1–2.

    Article  PubMed  Google Scholar 

  41. Levin, P. D. (1975). The effectiveness of various antibiotics in methyl methacrylate. Journal of Bone and Joint Surgery. British Volume (London), 57(2), 234–237.

    Article  CAS  Google Scholar 

  42. Logoluso, N., Drago, L., Gallazzi, E., et al. (2016). Calcium-based, antibiotic-loaded bone substitute as an implant coating: A pilot clinical study. Journal of Bone and Joint Infection, 1, 59–64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Antoci, V., Jr., Adams, C. S., Hickok, N. J., et al. (2007). Vancomycin bound to Ti rods reduces periprosthetic infection: Preliminary study. Clinical Orthopaedics and Related Research, 461, 88–95.

    PubMed  Google Scholar 

  44. Liu, L., Bhatia, R., & Webster, T. J. (2017). Atomic layer deposition of nano-TiO2 thin films with enhanced biocompatibility and antimicrobial activity for orthopedic implants. International Journal of Nanomedicine, 12, 8711–8723.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Jaggessar, A., Shahali, H., Mathew, A., et al. (2017). Bio-mimicking nano and micro-structured surface fabrication for antibacterial properties in medical implants. Journal of Nanobiotechnology, 15(1), 64.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Alt, V. (2017). Antimicrobial coated implants in trauma and orthopaedics-A clinical review and risk-benefit analysis. Injury, 48(3), 599–607.

    Article  PubMed  Google Scholar 

  47. Wahlig, H., Dingeldein, E., Bergmann, R., et al. (1978). The release of gentamicin from polymethylmethacrylate beads. An experimental and pharmacokinetic study. Journal of Bone and Joint Surgery. British Volume (London), 60-B(2), 270–275.

    Article  CAS  Google Scholar 

  48. Hardes, J., Gebert, C., Schwappach, A., et al. (2006). Characteristics and outcome of infections associated with tumor endoprostheses. Archives of Orthopaedic and Trauma Surgery, 126(5), 289–296.

    Article  CAS  PubMed  Google Scholar 

  49. Hardes, J., Henrichs, M. P., Hauschild, G., et al. (2017). Silver-coated megaprosthesis of the proximal tibia in patients with sarcoma. The Journal of Arthroplasty, 32(7), 2208–2213.

    Article  PubMed  Google Scholar 

  50. Fuchs, T., Stange, R., Schmidmaier, G., et al. (2011). The use of gentamicin-coated nails in the tibia: Preliminary results of a prospective study. Archives of Orthopaedic and Trauma Surgery, 131(10), 1419–1425.

    Article  PubMed  PubMed Central  Google Scholar 

  51. Schmidmaier, G., Kerstan, M., Schwabe, P., et al. (2017). Clinical experiences in the use of a gentamicin-coated titanium nail in tibia fractures. Injury, 48(10), 2235–2241.

    Article  CAS  PubMed  Google Scholar 

  52. Parvizi, J., Tan, T. L., Goswami, K., et al. (2018). The 2018 definition of periprosthetic hip and knee infection: An evidence-based and validated criteria. The Journal of Arthroplasty, 33(5), 1309–1314.e2.

    Article  PubMed  Google Scholar 

  53. Stoodley, P., Nistico, L., Johnson, S., et al. (2008). (2008) Direct demonstration of viable Staphylococcus aureus biofilms in an infected total joint arthroplasty. A case report. The Journal of Bone and Joint Surgery. American Volume, 90(8), 1751–1758.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Boucher, H. W., Wilcox, M., Talbot, G. H., et al. (2017). Once-weekly dalbavancin versus daily conventional therapy for skin infection. The New England Journal of Medicine, 370(23), 2169–2179.

    Article  CAS  Google Scholar 

  55. Sealed Envelope Ltd. (2012). Power calculator for binary outcome superiority trial. https://www.sealedenvelope.com/power/binary-superiority/

  56. Sendi, P., Rohrbach, M., Graber, P., et al. (2006). Staphylococcus aureus small colony variants in prosthetic joint infection. Clinical Infectious Diseases, 43(8), 961–967.

    Article  PubMed  Google Scholar 

  57. Romanò, C. L., Malizos, K., Capuano, N., et al. (2016). Does an antibiotic-loaded hydrogel coating reduce early post-surgical infection after joint arthroplasty? Journal of Bone and Joint Infection, 1, 34–41.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Malizos, K., Blauth, M., Danita, A., et al. (2017). Fast-resorbable antibiotic-loaded hydrogel coating to reduce post-surgical infection after internal osteosynthesis: A multicenter randomized controlled trial. Journal of Orthopaedics and Traumatology, 18(2), 159–169.

    Article  PubMed  PubMed Central  Google Scholar 

  59. Food and Drug Administration Center for Devices and Radiological Health. (2007). Draft guidance for industry and FDA staff – premarket notification [510(k)] submissions for medical devices that include antimicrobial agents. Retrieved from https://wayback.archive-it.org/7993/20180423155127/https://www.fda.gov/MedicalDevices/DeviceRegulationandGuidance/GuidanceDocuments/ucm071380.htm

  60. Kummer, K. M., Taylor, E. N., Durmas, N. G., et al. (2013). Effects of different sterilization techniques and varying anodized TiO2 nanotube dimensions on bacteria growth. Journal of Biomedical Materials Research. Part B, Applied Biomaterials, 101(5), 677–688.

    Article  CAS  PubMed  Google Scholar 

  61. Bagherifard, S., Hickey, D. J., de Luca, A. C., et al. (2015). The influence of nanostructured features on bacterial adhesion and bone cell functions on severely shot peened 316L stainless steel. Biomaterials, 73, 185–197.

    Article  CAS  PubMed  Google Scholar 

  62. Bhardwaj, G., & Webster, T. J. (2017). Reduced bacterial growth and increased osteoblast proliferation on titanium with a nanophase TiO2 surface treatment. International Journal of Nanomedicine, 12, 363–369.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Food and Drug Administration Center for Devices and Radiological Health. (2016). Guidance for industry and food and drug administration staff - Factors to consider when making benefit-risk determinations in medical device premarket approval and de novo classifications. Retrieved from https://www.fda.gov/downloads/medicaldevices/deviceregulationandguidance/guidancedocuments/ucm517504.pdf

  64. Phillips, K. S. (2018). What can we learn about medical device associated infection pathogenesis from skin explant models? Presentation at CBE Conference on Anti-Biofilm Technologies: Pathways to Product Development, Arlington VA, 7 Feb 2018.

    Google Scholar 

  65. From FDA web site: https://www.fda.gov/MedicalDevices/ScienceandResearch/ResearchPrograms/ucm477398.htm

  66. From FDA web site: https://www.fda.gov/AboutFDA/CentersOffices/OC/OfficeofScientificandMedicalPrograms/NCTR/WhatWeDo/ResearchDivisions/ucm079048.htm

Download references

Author information

Authors and Affiliations

  1. DePuy Synthes Biomaterials R&D, West Chester, PA, USA

    David A. Armbruster

Authors
  1. David A. Armbruster
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to David A. Armbruster .

Editor information

Editors and Affiliations

  1. Department of Veterans Affairs, Department of Orthopaedics, Department of Pathology, Department of Bioengineering, Department of Physical Medicine and Rehabilitation, University of Utah; Uniformed Services University of the Health Sciences, Salt Lake City, Bethesda, UT, USA

    Dustin L. Williams

Rights and permissions

Reprints and permissions

Copyright information

© 2019 Springer Nature Switzerland AG

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Armbruster, D.A. (2019). Biofilm Infections in Orthopedic Surgery and Their Impact on Commercial Product Development. In: Williams, D. (eds) Targeting Biofilms in Translational Research, Device Development, and Industrial Sectors. Springer, Cham. https://doi.org/10.1007/978-3-030-30667-0_2

Download citation

Publish with us

Policies and ethics

Search

Navigation