Local Antibacterial Implant Protection in Orthopedics and Trauma: What’s New?

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Abstract

Current prophylactic and hygienic measures notwithstanding, implant-related infection remains among leading reasons for failure in orthopaedics and trauma surgery, resulting in extremely high social and economic costs. Various antibacterial coating technologies have been proven safe and effective both in preclinical and in clinical settings and able to reduce post-surgical infections up to 90%, depending on the type of the coating and on the experimental setup. In spite of this findings, the widespread use of these technologies is still limited by several factors. After reviewing the latest evidence on currently available antibacterial coatings, an algorithm is proposed to calculate the impact of the delayed introduction of these technologies in the clinical practice. When applied to joint arthroplasties, our calculator shows that each year of delay to implement an antibacterial coating, able to reduce post-surgical infection by 80% at a final user’s cost price of €600, causes an estimated 35 200 new cases of periprosthetic joint infection in Europe and additional annual hospital costs of approximately €440 million. Faster and more affordable regulatory pathways for antibacterial coating technologies and an adequate reimbursement policy for their clinical use appear a feasible solution to mitigate the impact of implant-related infections and may benefit patients, healthcare systems, and related research.

All patients provided written informed consent.

Competing interests: the authors declare that there are no competing interests.

About the authors

C. L. Romanò

Studio Medico Associato Cecca-Romanò,
Romano Institute

Author for correspondence.
Email: carlo.romano@unimi.it

Carlo Luca Romanò — MD, Orthopaedic Consultant

Milan

Director 

Tirane, Albania

Italy

S. A. Bozhkova

Vreden Russian Research Institute of Traumatology and Orthopedics

Email: fake@neicon.ru

Svelana Bozhkova — Dr. Sci. (Med.), Head of the Research Department of Prevention and Treatment of Wound Infection and Department of Clinical Pharmacology

St. Petersburg

Russian Federation

V. Artyukh

Vreden Russian Research Institute of Traumatology and Orthopedics

Email: fake@neicon.ru

Vasilii Artyukh — Cand. Sci. (Med.), Head of Department

St. Petersburg

Russian Federation

D. Romanò

Studio Medico Associato Cecca-Romanò

Email: fake@neicon.ru

Delia Romanò — MD, Consultant

Milan

Italy

H. Tsuchiya

Graduate School of Medical Sciences, Kanazawa University

Email: fake@neicon.ru

Hiroyuki Tsuchiya — MD, PhD, Professor and Chairman, Department of Orthopaedic Surgery

Kanazawa

Japan

L. Drago

University of Milan

Email: fake@neicon.ru

Lorenzo Drago — PhD, Professor, Clinical Microbiology Department of Biomedical Sciences for Health

Milan

Italy

References

  1. Organisation for Economic Co-operation and Development (OECD), European Commission. Hip and knee replacement. In: Health at a Glance: Europe 2016: State of Health in the EU Cycle. Paris: OECD Publishing, 2016. pp. 172-173.
  2. Papin P., Berthonnaud E. Incidence of osteosynthesis of members in France. Int Orthop. 2017;41(8):1501-1506. doi: 10.1007/s00264-017-3502-6.
  3. Cats-Baril W., Gehrke T., Huff K., Kendoff D., Maltenfort M., Parvizi J. International consensus on periprosthetic joint infection: description of the consensus process. Clin Orthop Relat Res. 2013;471(12):4065-4075. doi: 10.1007/s11999-013-3329-4.
  4. Lenguerrand E., Whitehouse M.R., Beswick A.D., Toms A.D., Porter M.L., Blom A.W.; National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. Description of the rates, trends and surgical burden associated with revision for prosthetic joint infection following primary and revision knee replacements in England and Wales: an analysis of the National Joint Registry for England, Wales, Northern Ireland and the Isle of Man. BMJ Open. 2017;7(7):e014056. doi: 10.1136/bmjopen-2016-014056.
  5. Bonnevialle P., Bonnomet F., Philippe R., Loubignac F., Rubens-Duval B., Talbi A. et al.; SOFCOT. Early surgical site infection in adult appendicular skeleton trauma surgery: a multicenter prospective series. Orthop Traumatol Surg Res. 2012;98(6):684-689. doi: 10.1016/j.otsr.2012.08.002.
  6. Berbari E.F., Osmon D.R., Lahr B., Eckel-Passow J.E., Tsaras G., Hanssen A.D. et al. The Mayo prosthetic joint infection risk score: implication for surgical site infection reporting and risk stratification. Infect Control Hosp Epidemiol. 2012;33(8):774-781. doi: 10.1086/666641.
  7. Heppert V. Acute Infections After Osteosynthesis. In: European Instructional Lectures: Volume 12, 2012, 13th EFORT Congress, Berlin, Germany. Heidelberg: Springer-Verlag, 2012. pp. 25-31.
  8. Keene D.J., Mistry D., Nam J., Tutton E., Handley R., Morgan L. et al. The Ankle Injury Management (AIM) trial: a pragmatic, multicentre, equivalence randomized controlled trial and economic evaluation comparing close contact casting with open surgical reduction and internal fixation in the treatment of unstable ankle fractures in patients aged over 60 years. Health Technol Assess. 2016;20(75):1-158.
  9. Oliveira P.R., Carvalho V.C., da Silva Felix C., de Paula A.P., Santos-Silva J., Lima A.L. The incidence and microbiological profile of surgical site infections following internal fixation of closed and open fractures. Rev Bras Ortop. 2016;51(4):396-399. doi: 10.1016/j.rboe.2015.09.012.
  10. Shillingford J.N., Laratta J.L., Reddy H., Ha A., Lehman R.A. Jr., Lenke L.G., Fischer C.R. Postoperative Surgical Site Infection After Spine Surgery: An Update From the Scoliosis Research Society (SRS) Morbidity and Mortality Database. Spine Deform. 2018;6(6):634-643. doi: 10.1016/j.jspd.2018.04.004.
  11. Warner S.J., Uppstrom T.J., Miller A.O., O’Brien S.T., Salvatore C.M., Widmann R.F., Perlman S.L. Epidemiology of Deep Surgical Site Infections After Pediatric Spinal Fusion Surgery. Spine (Phila Pa 1976). 2017;42(3):E163-E168. doi: 10.1097/BRS.0000000000001735.
  12. Poultsides L.A., Liaropoulos L.L., Malizos K.N. The socioeconomic impact of musculoskeletal infections. J Bone Joint Surg Am. 2010;92(11):e13. doi: 10.2106/JBJS.I.01131.
  13. Kurtz S.M., Lau E., Watson H., Schmier J.K., Parvizi J. Economic burden of periprosthetic joint infection in the United States. J Arthroplasty. 2012;27(8 Suppl):61-65.e1. doi: 10.1016/j.arth.2012.02.022.
  14. Hernández-Vaquero D., Fernández-Fairen M., Torres A., Menzie A.M., Fernández-Carreira J.M., Murcia-Mazon A. et al. Treatment of periprosthetic infections: an economic analysis. ScientificWorldJournal. 2013;2013:821650. doi: 10.1155/2013/821650.
  15. Garrido-Gómez J., Arrabal-Polo M.A., Girón-Prieto M.S., Cabello-Salas J., Torres-Barroso J., Parra-Ruiz J. Descriptive analysis of the economic costs of periprosthetic joint infection of the knee for the public health system of Andalusia. J Arthroplasty. 2013;28(7):1057-1060. doi: 10.1016/j.arth.2013.02.012.
  16. Klouche S., Sariali E., Mamoudy P. Total hip arthroplasty revision due to infection: a cost analysis approach. Orthop Traumatol Surg Res. 2010;96(2):124-132. doi: 10.1016/j.rcot.2010.02.005.
  17. Haenle M., Skripitz C., Mittelmeier W., Skripitz R. Economic impact of infected total knee arthroplasty. ScientificWorldJournal. 2012;2012:196515. doi: 10.1100/2012/196515.
  18. Lieb E., Hanstein T., Schuerings M., Trampuz A., Perka C. [Reduction of Treatment Duration in Periprosthetic Infection with a Fast-Track Concept Is Economically Not Feasible]. Z Orthop Unfall. 2015;153(6):618-623. doi: 10.1055/s-0035-1557858. (In German).
  19. Vanhegan I.S., Malik A.K., Jayakumar P., Ul Islam S., Haddad F.S. A financial analysis of revision hip arthroplasty: the economic burden in relation to the national tariff. J Bone Joint Surg Br. 2012;94(5):619-623. doi: 10.1302/0301-620X.94B5.27073.
  20. Alp E., Cevahir F., Ersoy S., Guney A. Incidence and economic burden of prosthetic joint infections in a university hospital: A report from a middle-income country. J Infect Public Health. 2016;9(4):494-498. doi: 10.1016/j.jiph.2015.12.014.
  21. Kamath A.F., Ong K.L., Lau E., Chan V., Vail T.P., Rubash H.E. et al. Quantifying the Burden of Revision Total Joint Arthroplasty for Periprosthetic Infection. J Arthroplasty. 2015;30(9):1492-1497. doi: 10.1016/j.arth.2015.03.035.
  22. Romanò C.L., Romanò D., Logoluso N., Meani E. Septic versus aseptic hip revision: how different? J Orthop Traumatol. 2010;11(3):167-174. doi: 10.1007/s10195-010-0106-y.
  23. Parisi T.J., Konopka J.F., Bedair H.S. What is the Longterm Economic Societal Effect of Periprosthetic Infections After THA? A Markov Analysis. Clin Orthop Relat Res. 2017;475(7):1891-1900. doi: 10.1007/s11999-017-5333-6.
  24. Brochin R.L., Phan K., Poeran J., Zubizarreta N., Galatz L.M., Moucha C.S. Trends in Periprosthetic Hip Infection and Associated Costs: A Population-Based Study Assessing the Impact of Hospital Factors Using National Data. J Arthroplasty. 2018;33(7S):S233-S238. doi: 10.1016/j.arth.2018.02.062.
  25. Gristina A.G., Naylor P., Myrvik Q. Infections from biomaterials and implants: a race for the surface. Med Prog Technol. 1988-1989;14(3-4):205-224.
  26. Gristina A.G., Shibata Y., Giridhar G., Kreger A., Myrvik Q.N. The glycocalyx, biofilm, microbes, and resistant infection. Semin Arthroplasty. 1994;5(4):160-170.
  27. Dastgheyb S., Parvizi J., Shapiro I.M., Hickok N.J., Otto M. Effect of biofilms on recalcitrance of staphylococcal joint infection to antibiotic treatment. J Infect Dis. 2015;211(4):641-650. doi: 10.1093/infdis/jiu514.
  28. Holá V, Růžička F, Votava M. The dynamics of staphylococcus epidermis biofilm formation in relation to nutrition, temperature Effect of biofilms on recalcitrance of staphylococcal joint infection to antibiotic treatment, and time. Scripta Medica Facultatis Medicae Universitatis Brunensis Masarykianae. 2006;79:169-174.
  29. Chandki R., Banthia P., Banthia R. Biofilms: A microbial home. J Indian Soc Periodontol. 2011;15(2):111-114. doi: 10.4103/0972-124X.84377.
  30. Qin S., Xu K., Nie B., Ji F., Zhang H. Approaches based on passive and active antibacterial coating on titanium to achieve antibacterial activity. J Biomed Mater Res A. 2018;106(9):2531-2539. doi: 10.1002/jbm.a.36413.
  31. Romanò C.L., Scarponi S., Gallazzi E., Romanò D., Drago L. Antibacterial coating of implants in orthopaedics and trauma: a classification proposal in an evolving panorama. J Orthop Surg Res. 2015;10:157. doi: 10.1186/s13018-015-0294-5.
  32. Moriarty T.F., Grainger D.W., Richards R.G. Challenges in linking preclinical anti-microbial research strategies with clinical outcomes for device-associated infections. Eur Cell Mater. 2014;28:112-128; discussion 128.
  33. Alt V. Antimicrobial coated implants in trauma and orthopaedics-A clinical review and risk-benefit analysis. Injury. 2017;48(3):599-607. doi: 10.1016/j.injury.2016.12.011.
  34. Chernousova S., Epple M. Silver as antibacterial agent: ion, nanoparticle, and metal. Angew Chem Int Ed Engl. 2013;52(6):1636-1653. doi: 10.1002/anie.201205923.
  35. Schmidt-Braekling T., Streitbuerger A., Gosheger G., Boettner F., Nottrott M., Ahrens H., Dieckmann R, Guder W, Andreou D, Hauschild G, Moellenbeck B, Waldstein W, Hardes J. Silver-coated megaprostheses: review of the literature. Eur J Orthop Surg Traumatol. 2017;27(4):483-489. doi: 10.1007/s00590-017-1933-9.
  36. Hardes J., von Eiff C., Streitbuerger A., Balke M., Budny T., Henrichs M. et al. Reduction of periprosthetic infection with silver-coated megaprostheses in patients with bone sarcoma. J Surg Oncol. 2010;101(5):389-395. doi: 10.1002/jso.21498.
  37. Hardes J., Henrichs M.P., Hauschild G., Nottrott M., Guder W., Streitbuerger A. Silver-Coated Megaprosthesis of the Proximal Tibia in Patients With Sarcoma. J Arthroplasty. 2017;32(7):2208-2213. doi: 10.1016/j.arth.2017.02.054.
  38. Wafa H., Grimer R.J., Reddy K., Jeys L., Abudu A., Carter S.R., Tillman R.M. Retrospective evaluation of the incidence of early periprosthetic infection with silver-treated endoprostheses in high-risk patients: case-control study. Bone Joint J. 2015;97-B(2):252-257. doi: 10.1302/0301-620X.97B2.34554.
  39. Mijnendonckx K., Leys N., Mahillon J., Silver S., Van Houdt R. Antimicrobial silver: uses, toxicity and potential for resistance. Biometals. 2013;26(4):609-621. doi: 10.1007/s10534-013-9645-z.
  40. Trentinaglia M.T., Van Der Straeten C., Morelli I., Logoluso N., Drago L., Romanò C.L. Economic Evaluation of Antibacterial Coatings on Healthcare Costs in First Year Following Total Joint Arthroplasty. J Arthroplasty. 2018;33(6):1656-1662. doi: 10.1016/j.arth.2018.01.057.
  41. Shirai T., Shimizu T., Ohtani K., Zen Y., Takaya M., Tsuchiya H. Antibacterial iodine-supported titanium implants. Acta Biomater. 2011;7(4):1928-1933. doi: 10.1016/j.actbio.2010.11.036.
  42. Inoue D., Kabata T., Ohtani K., Kajino Y., Shirai T., Tsuchiya H. Inhibition of biofilm formation on iodine-supported titanium implants. Int Orthop. 2017;41(6):1093-1099. doi: 10.1007/s00264-017-3477-3.
  43. Inoue D., Kabata T., Kajino Y., Shirai T., Tsuchiya H. Iodine-supported titanium implants have good antimicrobial attachment effects. J Orthop Sci. 2019;24(3): 548-551. doi: 10.1016/j.jos.2018.10.010.
  44. Tsuchiya H., Shirai T., Nishida H., Murakami H., Kabata T., Yamamoto N. et al. Innovative antimicrobial coating of titanium implants with iodine. J Orthop Sci. 2012;17(5):595-604. doi: 10.1007/s00776-012-0247-3.
  45. Shirai T., Tsuchiya H., Nishida H., Yamamoto N., Watanabe K., Nakase J. et al. Antimicrobial megaprostheses supported with iodine. J Biomater Appl. 2014;29(4):617-623. doi: 10.1177/0885328214539365.
  46. Kabata T., Maeda T., Kajino Y., Hasegawa K., Inoue D., Yamamoto T. et al. Iodine-supported hip implants: short term clinical results. BioMed Res Int. 2015;2015. Article ID 368124, 6 pages. doi: 10.1155/2015/368124.
  47. Schmidmaier G., Wildemann B., Stemberger A., Haas N.P., Raschke M. Biodegradable poly(D,L-lactide) coating of implants for continuous release of growth factors. J Biomed Mater Res. 2001;58(4):449-455. doi: 10.1002/jbm.1040.
  48. Fuchs T., Stange R., Schmidmaier G., Raschke M.J. The use of gentamicin-coated nails in the tibia: preliminary results of a prospective study. Arch Orthop Trauma Surg. 2011;131(10):1419-1425. doi: 10.1007/s00402-011-1321-6.
  49. Metsemakers W.J., Reul M., Nijs S. The use of gentamicincoated nails in complex open tibia fracture and revision cases: A retrospective analysis of a single centre case series and review of the literature. Injury. 2015;46(12): 2433-2437. doi: 10.1016/j.injury.2015.09.028.
  50. Schmidmaier G., Kerstan M., Schwabe P., Südkamp N., Raschke M. Clinical experiences in the use of a gentamicin-coated titanium nail in tibia fractures. Injury. 2017;48(10):2235-2241. doi: 10.1016/j.injury.2017.07.008.
  51. Schmitz F.J., Verhoef J., Fluit A.C. Prevalence of aminoglycoside resistance in 20 European university hospitals participating in the European SENTRY Antimicrobial Surveillance Programme. Eur J Clin Microbiol Infect Dis. 1999;18(6):414-421.
  52. Drago L., Boot W., Dimas K., Malizos K., Hänsch G.M., Stuyck J. et al. Does implant coating with antibacterialloaded hydrogel reduce bacterial colonization and biofilm formation in vitro? Clin Orthop Relat Res. 2014;472(11): 3311-3323. doi: 10.1007/s11999-014-3558-1.
  53. Romanò C.L., De Vecchi E., Bortolin M., Morelli I., Drago L. Hyaluronic Acid and Its Composites as a Local Antimicrobial/Antiadhesive Barrier. J Bone Jt Infect. 2017;2(1):63-72. doi: 10.7150/jbji.17705.
  54. Ardizzoni A., Neglia R.G., Baschieri M.C., Cermelli C., Caratozzolo M., Righi E. et al. Influence of hyaluronic acid on bacterial and fungal species, including clinically relevant opportunistic pathogens. J Mater Sci Mater Med. 2011;22(10):2329-2338. doi: 10.1007/s10856-011-4408-2.
  55. Pavesio A., Renier D., Cassinelli C., Morra M. Antiadhesive surfaces through hyaluronan coatings. Med Device Technol. 1997;8(7):20-21, 24-27.
  56. Morra M., Cassineli C. Non-fouling properties of polysaccharide-coated surfaces. J Biomater Sci Polym Ed. 1999;10(10):1107-1124.
  57. Giavaresi G., Meani E., Sartori M., Ferrari A., Bellini D., Sacchetta A.C. et al. Efficacy of antibacterial-loaded coating in an in vivo model of acutely highly contaminated implant. Int Orthop. 2014;38(7):1505-1512. doi: 10.1007/s00264-013-2237-2.
  58. Boot W., Vogely H.Ch., Nikkels P.G.J., Dhert W., Gawlitta D. Local prophylaxis of implant-related infections using a hydrogel as carrier. Eur Cell Mater. 2015;30:19.
  59. Boot W., Gawlitta D., Nikkels P.G.J., Pouran B., van Rijen M.H.P., Dhert W.J.A, Vogely H.C. Hyaluronic Acid-Based Hydrogel Coating Does Not Affect Bone Apposition at the Implant Surface in a Rabbit Model. Clin Orthop Relat Res. 2017;475(7):1911-1919. doi: 10.1007/s11999-017-5310-0.
  60. Romanò C.L., Malizos K., Capuano N., Mezzoprete R., D’Arienzo M., Van Der Straeten C. et al. Does an Antibiotic-Loaded Hydrogel Coating Reduce Early Post-Surgical Infection After Joint Arthroplasty? J Bone Jt Infect. 2016;1:34-41. doi: 10.7150/jbji.15986.
  61. Malizos K., Blauth M., Danita A., Capuano N., Mezzoprete R., Logoluso N. et al. Fast-resorbable antibiotic-loaded hydrogel coating to reduce post-surgical infection after internal osteosynthesis: a multicenter randomized controlled trial. J Orthop Traumatol. 2017;18(2):159-169. doi: 10.1007/s10195-017-0442-2.
  62. Capuano N., Logoluso N., Gallazzi E., Drago L., Romanò C.L. One-stage exchange with antibacterial hydrogel coated implants provides similar results to two-stage revision, without the coating, for the treatment of peri-prosthetic infection. Knee Surg Sports Traumatol Arthrosc. 2018;26(11):3362-3367. doi: 10.1007/s00167-018-4896-4.
  63. Graves N., Wloch C., Wilson J., Barnett A., Sutton A., Cooper N. et al. A cost-effectiveness modelling study of strategies to reduce risk of infection following primary hip replacement based on a systematic review. Health Technol Assess. 2016;20(54):1-144. doi: 10.3310/hta20540.
  64. Shearer D.W., Youm J., Bozic K.J. Short-term complications have more effect on cost-effectiveness of THA than implant longevity. Clin Orthop Relat Res. 2015;473(5): 1702-1708. doi: 10.1007/s11999-014-4110-z.
  65. Romanò C.L., Tsuchiya H., Morelli I., Battaglia A.G., Drago L. Antibacterial coating of implants: are we missing something? Bone Joint Res. 2019;8(5):199-206. doi: 10.1302/2046-3758.85.BJR-2018-0316.

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