1887

Abstract

Purpose. Antibiotic-loaded polymethylmethacrylate-based bone cement has been implemented in orthopaedics to cope with implant-related infections associated with the formation of bacterial biofilms. In the context of emerging bacterial resistance to current antibiotics, we examined the efficacy of short antimicrobial peptide-loaded bone cement in inhibiting bacterial adhesion and consequent biofilm formation on its surface.

Methodology. The ability of α-helical antimicrobial peptides composed of 12 amino acid residues to prevent bacterial biofilm [methicillin-resistant Staphylococcus aureus (MRSA), Staphylococcus epidermidis , Pseudomonas aeruginosa and Escherichia coli ] formation on the surface of model implants made from polymethylmethacrylate-based bone cement was evaluated by colony-forming unit (c.f.u.) counting of bacteria released by sonication from the biofilms formed on their surfaces. The biofilms on model implant surfaces were also visualized by light microscopy after staining with tetrazolium dye (MTT) and by scanning electron microscopy.

Results. When incorporated in the implants, these peptides caused a mean reduction in the number of bacterial cells attached to implants’ surfaces (by five orders of magnitude), and 88 % of these implants showed no bacterial adhesion after being exposed to growth media containing various bacteria.

Conclusion. The results showed that the antibiofilm activity of these peptides was comparable to that of the antibiotics, but the peptides exhibited broader specificity than the antibiotics. Given the rapid development of antibiotic resistance, antimicrobial peptides show promise as a substitute for antibiotics for loading into bone cements.

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2019-05-20
2024-04-27
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References

  1. Ribeiro M, Monteiro FJ, Ferraz MP. Infection of orthopedic implants with emphasis on bacterial adhesion process and techniques used in studying bacterial-material interactions. Biomaterials 2012; 2:176–194
    [Google Scholar]
  2. Benito N, Franco M, Ribera A, Soriano A, Rodriguez-Pardo D et al. Time trends in the aetiology of prosthetic joint infections: a multicentre cohort study. Clin Microbiol Infect 2016; 22:732.e1–e8 [View Article]
    [Google Scholar]
  3. Costerton JW. Biofilm theory can guide the treatment of device-related orthopaedic infections. Clin Orthop Relat Res 2005; 437:7–11 [View Article]
    [Google Scholar]
  4. Li B, Webster TJ. Bacteria antibiotic resistance: new challenges and opportunities for implant-associated orthopaedic infections. J Orthop Res 2018; 36:22–32
    [Google Scholar]
  5. Kendoff DO, Gehrke T, Stangenberg P, Frommelt L, Bösebeck H. Bioavailability of gentamicin and vancomycin released from an antibiotic containing bone cement in patients undergoing a septic one-stage total hip arthroplasty (THA) revision: a monocentric open clinical trial. HIP Int 2016; 26:90–96 [View Article]
    [Google Scholar]
  6. Jahoda D, Sosna A, Nyč O et al. Treatment of prosthetic joint infections. , 1st ed. Praha: TRITON 2010; pp 108–112
  7. Winkler H, Haiden P. Treatment of chronic bone infection. Oper Tech Orthop 2016; 26:2–11 [View Article]
    [Google Scholar]
  8. Getzlaf MA, Lewallen EA, Kremers HM, Jones DL, Bonin CA et al. Multi-disciplinary antimicrobial strategies for improving orthopaedic implants to prevent prosthetic joint infections in hip and knee. J Orthop Res 2016; 34:177–186 [View Article]
    [Google Scholar]
  9. Birt MC, Anderson DW, Bruce Toby E, Wang J. Osteomyelitis: recent advances in pathophysiology and therapeutic strategies. J Orthop 2017; 14:45–52 [View Article]
    [Google Scholar]
  10. Campoccia D, Montanaro L, Speziale P, Arciola CR. Antibiotic-loaded biomaterials and the risks for the spread of antibiotic resistance following their prophylactic and therapeutic clinical use. Biomaterials 2010; 31:6363–6377 [View Article]
    [Google Scholar]
  11. Hake ME, Young H, Hak DJ, Stahel PF, Hammerberg EM et al. Local antibiotic therapy strategies in orthopaedic trauma: practical tips and tricks and review of the literature. Injury 2015; 46:1447–1456 [View Article]
    [Google Scholar]
  12. Gogia JS, Meehan JP, Di Cesare PE, Jamali AA. Local antibiotic therapy in osteomyelitis. Semin Plast Surg 2009; 23:100–107 [View Article]
    [Google Scholar]
  13. Lewis G. Properties of antibiotic-loaded acrylic bone cements for use in cemented arthroplasties: a state-of-the-art review. J Biomed Mater Res B Appl Biomater 2009; 89:558–574 [View Article]
    [Google Scholar]
  14. Ma D, Shanks RMQ, Davis CM, Craft DW, Wood TK et al. Viable bacteria persist on antibiotic spacers following two-stage revision for periprosthetic joint infection. J Orthop Res 2018; 36:452–458
    [Google Scholar]
  15. Anagnostakos K, Hitzler P, Pape D, Kohn D, Kelm J. Persistence of bacterial growth on antibiotic-loaded beads: is it actually a problem?. Acta Orthop 2008; 79:302–307 [View Article]
    [Google Scholar]
  16. Brogden NK, Brogden KA. Will new generations of modified antimicrobial peptides improve their potential as pharmaceuticals?. Int J Antimicrob Agents 2011; 38:217–225
    [Google Scholar]
  17. Baltzer SA, Brown MH. Antimicrobial peptides – promising alternatives to conventional antibiotics. J Mol Microbiol Biotechnol 2011; 20:228–235 [View Article]
    [Google Scholar]
  18. Yeaman MR, Yount NY. Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 2003; 55:27–55 [View Article]
    [Google Scholar]
  19. Mishra B, Reiling S, Zarena D, Wang G. Host defense antimicrobial peptides as antibiotics: design and application strategies. Curr Opin Chem Biol 2017; 38:87–96 [View Article]
    [Google Scholar]
  20. Nguyen LT, Haney EF, Vogel HJ. The expanding scope of antimicrobial peptide structures and their modes of action. Trends Biotechnol 2011; 29:464–472 [View Article]
    [Google Scholar]
  21. Zhang LJ, Gallo RL. Antimicrobial peptides. Curr Biol 2016; 26:R14–R19 [View Article]
    [Google Scholar]
  22. Pletzer D, Hancock REW. Antibiofilm peptides: potential as broad-spectrum agents. J Bacteriol 2016; 198:2572–2578 [View Article]
    [Google Scholar]
  23. Mishra B, Wang G. Individual and combined effects of engineered peptides and antibiotics on Pseudomonas aeruginosa biofilms. Pharmaceuticals 2017; 10:58 [View Article]
    [Google Scholar]
  24. Laverty G, Gorman SP, Gilmore BF. Antimicrobial peptide incorporated poly(2-hydroxyethyl methacrylate) hydrogels for the prevention of Staphylococcus epidermidis-associated biomaterial infections. J Biomed Mater Res A 2012; 100:1803–1814 [View Article]
    [Google Scholar]
  25. Faber C, Hoogendoorn RJW, Stallmann HP, Lyaruu DM, van Nieuw Amerongen A et al. In vivo comparison of Dhvar-5 and gentamicin in an MRSA osteomyelitis prevention model. J Antimicrob Chemother 2004; 54:1078–1084 [View Article]
    [Google Scholar]
  26. Faber C, Stallmann HP, Lyaruu DM, de Blieck JMA, Bervoets TJM. Release of antimicrobial peptide Dhvar-5 from polymethylmethacrylate beads. J Antimicrob Chemother 2003; 51:1359–1364 [View Article]
    [Google Scholar]
  27. Gálvez-López R, Peña-Monje A, Antelo-Lorenzo R, Guardia-Olmedo J, Moliz J et al. Elution kinetics, antimicrobial activity, and mechanical properties of 11 different antibiotic loaded acrylic bone cement. Diagn Microbiol Infect Dis 2014; 78:70–74 [View Article]
    [Google Scholar]
  28. Slane J, Gietman B, Squire M. Antibiotic elution from acrylic bone cement loaded with high doses of tobramycin and vancomycin. J Orthop Res 2018; 36:1078–1085
    [Google Scholar]
  29. Lee SH, Tai CL, Chen SY, Chang CH, Chang YH et al. Elution and mechanical strength of vancomycin-loaded bone cement: invitro study of the influence of brand combination. Plos One 2016; 11:e0166545 [View Article]
    [Google Scholar]
  30. Bishop AR, Kim S, Squire MW, Rose WE, Ploeg HL. Vancomycin elution, activity and impact on mechanical properties when added to orthopedic bone cement. J Mech Behav Biomed Mater 2018; 87:80–86 [View Article]
    [Google Scholar]
  31. Bertazzoni Minelli E, Della Bora T, Benini A. Different microbial biofilm formation on polymethylmethacrylate (PMMA) bone cement loaded with gentamicin and vancomycin. Anaerobe 2011; 17:380–383 [View Article]
    [Google Scholar]
  32. Melicherčík P, Nešuta O, Čeřovský V. Antimicrobial peptides for topical treatment of osteomyelitis and implant-related infections: study in the spongy bone. Pharmaceuticals 2018; 11:20 [View Article]
    [Google Scholar]
  33. Monincová L, Buděšínský M, Slaninová J, Hovorka O, Cvačka J et al. Novel antimicrobial peptides from the venom of the eusocial bee Halictus sexcinctus (Hymenoptera: Halictidae) and their analogs. Amino Acids 2010; 39:763–775 [View Article]
    [Google Scholar]
  34. Nešuta O, Buděšínský M, Hadravová R, Monincová L, Humpoličková J et al. How proteases from Enterococcus faecalis contribute to its resistance to short α-helical antimicrobial peptides. Pathog Dis 2017; 75:ftx091 [View Article]
    [Google Scholar]
  35. Zaatreh S, Wegner K, Strauß M, Pasold J, Mittelmeier W et al. Co-culture of S. epidermidis and human osteoblasts on implant surfaces: an advanced in vitro model for implant-associated infections. Plos One 2016; 11:e0151534 [View Article]
    [Google Scholar]
  36. Anagnostakos K, Fürst O, Kelm J. Antibiotic-impregnated PMMA hip spacers: current status. Acta Orthop 2006; 77:628–637 [View Article]
    [Google Scholar]
  37. Webb JCJ, Spencer RF. The role of polymethylmethacrylate bone cement in modern orthopaedic surgery. J Bone Joint Surg Br 2007; 89:851–857 [View Article]
    [Google Scholar]
  38. Yuenyongviwat V, Ingviya N, Pathaburee P, Tangtrakulwanich B. Inhibitory effects of vancomycin and fosfomycin on methicillin-resistant Staphylococcus aureus from antibiotic-impregnated articulating cement spacers. Bone Joint Res 2017; 6:132–136 [View Article]
    [Google Scholar]
  39. Anagnostakos K, Wilmes P, Schmitt E, Kelm J. Elution of gentamicin and vancomycin from polymethylmethacrylate beads and hip spacers in vivo. Acta Orthop 2009; 80:193–197 [View Article]
    [Google Scholar]
  40. Anagnostakos K, Meyer C. Antibiotic elution from hip and knee acrylic bone cement spacers: a systematic review. Biomed Res Int 2017; 2017:4657874 [View Article]
    [Google Scholar]
  41. Bertazzoni Minelli E, Benini A, Samaila E, Bondi M, Magnan B. Antimicrobial activity of gentamicin and vancomycin combination in joint fluids after antibiotic-loaded cement spacer implantation in two-stage revision surgery. J Chemother 2015; 27:17–24 [View Article]
    [Google Scholar]
  42. Giangaspero A, Sandri L, Tossi A. Amphipathic α-helical antimicrobial peptides. A systematic study of the effects of structural and physical properties on biological activity. Eur J Biochem 2001; 268:5589–5600
    [Google Scholar]
  43. Hazam PK, Jerath G, Kumar A, Chaudhary N, Ramakrishnan V. Effect of tacticity-derived topological constraints in bactericidal peptides. Biochim Biophys Acta Biomembr 2017; 1859:1388–1395 [View Article]
    [Google Scholar]
  44. Bistolfi A, Massazza G, Verné E, Maseé A, Deledda D et al. Antibiotic-loaded cement in orthopedic surgery: a review. ISRN Orthop 2011; 290851:
    [Google Scholar]
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