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Cell and Tissue Banking

, Volume 15, Issue 1, pp 139–144 | Cite as

Gentamicin palmitate as a new antibiotic formulation for mixing with bone tissue and local release

  • Débora C. Coraça-HuberEmail author
  • David Putzer
  • Manfred Fille
  • Johann Hausdorfer
  • Michael Nogler
  • Klaus-Dieter Kühn
Original Paper

Abstract

During surgery with bone grafting, the impaction of bone tissue creates an avascular area where local circulation is disrupted. If infections arise, they may prevent systemically administered antibiotics from reaching the infected bone. In this study we evaluated gentamicin palmitate (GP) mixed with gentamicin sulfate (GS) as a coating for bone chips (BCh). The efficacy of the coated BCh was measured by gentamicin base release tests using B. subtilis, S. epidermidis and S. aureus. Gentamicin base release was evaluated in phosphate-buffered saline for up to 7 days using B. subtilis bioassay. Antimicrobial efficacy was tested with S. aureus and S. epidermidis. A significant difference on the release of gentamicin base between GS and GS + GP was observed. S. epidermidis are significantly more susceptible to GS + GP and GS than S. aureus. BCh can act as gentamicin carriers and showed efficacy against S. aureus and S. epidermidis.

Keywords

Bone allografts Anti-infective coating Gentamicin palmitate Bacillus subtilis Staphylococcus aureus Staphylococcus epidermidis 

Notes

Acknowledgments

We thank Dennis Huber, Experimental Orthopedics, Medical University Innsbruck and Sebastian Vogt from Heraeus Medical GmbH for their comments and improvement of this manuscript This study was funded by Heraeus Medical GmbH, Wehrheim, Germany. Dr. Débora C. Coraça-Huber, Dr. David Putzer and Dr. Michael Nogler are paid employees of Medical University Innsbruck, Experimental Orthopedics. Dr. Manfred Fille and Dr. Hausdorfer are paid employees of Medical University Innsbruck, Division of Hygiene and Medical Microbiology. Dr. Klaus-Dieter Kühn is paid employee by Heraeus Medical GmbH.

References

  1. Barbour SA, King W (2003) The safe and effective use of allograft tissue–an update. Am J Sports Med 31(5):791–797PubMedGoogle Scholar
  2. Blom AW, Taylor AH, Pattison G, Whitehouse S, Bannister GC (2003) Infection after total hip arthroplasty. the avon experience. J Bone Joint Surg Br 85(7):956–959PubMedCrossRefGoogle Scholar
  3. Brewster NT, Gillespie WJ, Howie CR, Madabhushi SP, Usmani AS, Fairbairn DR (1999) Mechanical considerations in impaction bone grafting. J Bone Joint Surg Br 81(1):118–124PubMedCrossRefGoogle Scholar
  4. Butler AM, Morgan DA, Verheul R, Walsh WR (2005) Mechanical properties of gamma irradiated morselized bone during compaction. Biomaterials 26(30):6009–6013. doi: 10.1016/j.biomaterials.2005.03.007 PubMedCrossRefGoogle Scholar
  5. Buttaro MA, Gonzalez Della Valle AM, Pineiro L, Mocetti E, Morandi AA, Piccaluga F (2003) Incorporation of vancomycin-supplemented bone incorporation of vancomycin-supplemented bone allografts: radiographical, histopathological and immunohistochemical study in pigs. Acta Orthop Scand 74(5):505–513. doi: 10.1080/00016470310017884 PubMedCrossRefGoogle Scholar
  6. Buttaro MA, Gimenez MI, Greco G, Barcan L, Piccaluga F (2005) High active local levels of vancomycin without nephrotoxicity released from impacted bone allografts in 20 revision hip arthroplasties. Acta Orthop 76(3):336–340. doi: 10.1080/00016470510030797 PubMedGoogle Scholar
  7. Christensen G, Baddour L, Hasty D, Lowrance J, SImpson W (1989) Microbial and foreign body factors in the pathogenesis of medical device infections. American Society for MicrobiologyGoogle Scholar
  8. Coraca-Huber DC, Fille M, Hausdorfer J, Pfaller K, Nogler M (2012) Evaluation of MBEC-HTP biofilm model for studies of implant associated infections. J Orthop Res 30(7):1176–1180. doi: 10.1002/jor.22065 PubMedCrossRefGoogle Scholar
  9. Haimi S, Vienonen A, Hirn M, Pelto M, Virtanen V, Suuronen R (2008) The effect of chemical cleansing procedures combined with peracetic acid-ethanol sterilization on biomechanical properties of cortical bone. Biologicals 36(2):99–104. doi: 10.1016/j.biologicals.2007.06.001 PubMedCrossRefGoogle Scholar
  10. Hinsenkamp M, Muylle L, Eastlund T, Fehily D, Noel L, Strong DM (2012) Adverse reactions and events related to musculoskeletal allografts: reviewed by the World Health Organisation Project NOTIFY. Int Orthop 36(3):633–641. doi: 10.1007/s00264-011-1391-7 PubMedCentralPubMedCrossRefGoogle Scholar
  11. Hofmann A, Konrad L, Hessmann MH, Kuchle R, Korner J, Rompe JD, Rommens PM (2005) The influence of bone allograft processing on osteoblast attachment and function. J Orthop Res 23(4):846–854. doi: 10.1016/j.orthres.2004.11.012 PubMedCrossRefGoogle Scholar
  12. Isefuku S, Joyner CJ, Simpson AH (2003) Gentamicin may have an adverse effect on osteogenesis. J Orthop Trauma 17(3):212–216PubMedCrossRefGoogle Scholar
  13. Kühn K, Vogt S, Schnabelrauch M. (2003) Porous implants with antibiotic coating, their preparation and use. EP 1374923 B1Google Scholar
  14. Kuhn KD, Weber C, Kreis S, Holzgrabe U (2008) Evaluation of the stability of gentamicin in different antibiotic carriers using a validated MEKC method. J Pharm Biomed Anal 48(3):612–618. doi: 10.1016/j.jpba.2008.05.041 PubMedCrossRefGoogle Scholar
  15. Matl FD, Obermeier A, Repmann S, Friess W, Stemberger A, Kuehn KD (2008) New anti-infective coatings of medical implants. Antimicrob Agents Chemother 52(6):1957–1963. doi: 10.1128/AAC.01438-07 PubMedCentralPubMedCrossRefGoogle Scholar
  16. Matl FD, Zlotnyk J, Obermeier A, Friess W, Vogt S, Buchner H, Schnabelrauch H, Stemberger A, Kuhn KD (2009) New anti-infective coatings of surgical sutures based on a combination of antiseptics and fatty acids. J Biomater Sci Polym Ed 20(10):1439–1449. doi: 10.1163/092050609X12457418973107 PubMedCrossRefGoogle Scholar
  17. N/A (2011) Deutsches Institut für Normung. DIN 18123: soil, investigation and testing—Determination of grain-size distribution. http://www.din.de/cmd?level=tpl-home&contextid=din. Accessed 07.2012 2012
  18. Parrish FF (1973) Allograft replacement of all or part of the end of a long bone following excision of a tumor. J Bone Joint Surg Am 55(1):1–22PubMedGoogle Scholar
  19. Parvizi J, Pour AE, Keshavarzi NR, D’Apuzzo M, Sharkey PF, Hozack WJ (2007) Revision total hip arthroplasty in octogenarians. A case-control study. J Bone Joint Surg Am 89(12):2612–2618. doi: 10.2106/JBJS.F.00881 PubMedCrossRefGoogle Scholar
  20. Parvizi J, Saleh KJ, Ragland PS, Pour AE, Mont MA (2008) Efficacy of antibiotic-impregnated cement in total hip replacement. Acta Orthop 79(3):335–341. doi: 10.1080/17453670710015229 PubMedCrossRefGoogle Scholar
  21. Putzer D, Mayr E, Haid C, Reinthaler A, Nogler M (2011) Impaction bone grafting: a laboratory comparison of two methods. J Bone Joint Surg Br 93(8):1049–1053. doi: 10.1302/0301-620X.93B8.26819 PubMedCrossRefGoogle Scholar
  22. Saraf SK, Yadav A, Nagwani S, Sen M (2010) Decal bone matrix as a local antibiotic delivery vehicle in a MRSA-infected bone model: an experimental study. Indian J Orthop 44(3):246–251. doi: 10.4103/0019-5413.65140 PubMedCentralPubMedCrossRefGoogle Scholar
  23. Sorger JI, Hornicek FJ, Zavatta M, Menzner JP, Gebhardt MC, Tomford WW, Mankin HJ (2001) Allograft fractures revisited. Clin Orthop Relat Res 382:66–74PubMedCrossRefGoogle Scholar
  24. Stevens CM, Tetsworth KD, Calhoun JH, Mader JT (2005) An articulated antibiotic spacer used for infected total knee arthroplasty: a comparative in vitro elution study of Simplex and Palacos bone cements. J Orthop Res 23(1):27–33. doi: 10.1016/j.orthres.2004.03.003 PubMedCrossRefGoogle Scholar
  25. Winkler H, Janata O, Berger C, Wein W, Georgopoulos A (2000) In vitro release of vancomycin and tobramycin from impregnated human and bovine bone grafts. J Antimicrob Chemother 46(3):423–428PubMedCrossRefGoogle Scholar
  26. Witso E, Persen L, Benum P, Bergh K (2005) Cortical allograft as a vehicle for antibiotic delivery. Acta Orthop 76(4):481–486. doi: 10.1080/17453670510041457 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  • Débora C. Coraça-Huber
    • 1
    Email author
  • David Putzer
    • 1
  • Manfred Fille
    • 4
  • Johann Hausdorfer
    • 4
  • Michael Nogler
    • 1
  • Klaus-Dieter Kühn
    • 2
    • 3
  1. 1.Experimental OrthopaedicsMedical University InnsbruckInnsbruckAustria
  2. 2.Heraeus Medical GmbHWehrheimGermany
  3. 3.Department of OrthopaedicsMedical University GrazGrazAustria
  4. 4.Division of Hygiene and Medical MicrobiologyMedical University InnsbruckInnsbruckAustria

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