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Coating with a novel gentamicinpalmitate formulation prevents implant-associated osteomyelitis induced by methicillin-susceptible Staphylococcus aureus in a rat model

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Abstract

Purpose

Implant-associated osteomyelitis still represents a demanding challenge due to unfavourable biological conditions, bacterial properties and incremental resistance to antibiotic treatment. Therefore different bactericide or bacteriostatic implant coatings have been developed recently to control local intramedullary infections. Controlled local release of gentamicin base from a highly lipophilic gentamicin palmitate compound achieves extended intramedullary retention times and thus may improve its bactericide effect.

Methods

Forty male Sprague-Dawley rats were divided into two groups receiving an intramedullary femoral injection of 102 colony-forming units (CFU) of a common methicillin susceptible Staphylococcus aureus strain (MSSA Rosenbach) and either an uncoated femur nail (Group I) or a nail coated with gentamicin palmitate (Group II). Animals were observed for 28 and 42 days. Serum haptoglobin and relative weight gain were assessed as well as rollover cultures of explanted femur nails and histological scores of periprosthetic infection in dissected femurs.

Results

Implants coated with gentamicin palmitate significantly reduced periprosthetic bacterial growth as well as signs of systemic inflammation compared with uncoated implants.

Conclusions

Gentamicin palmitate appears to be a viable coating for the prevention of implant-associated infections. These findings will have to be confirmed in larger animal models as well as in clinical trials.

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References

  1. Uçkay I, Jugun K, Gamulin A et al (2012) Chronic osteomyelitis. Curr Infect Dis Rep 14:566–575

    Article  PubMed  Google Scholar 

  2. Li G-Q, Guo F-F, Ou Y et al (2013) Epidemiology and outcomes of surgical site infections following orthopedic surgery. Am J Infect Control 41:1268–1271

    Article  PubMed  Google Scholar 

  3. Chang Y, Tai C-L, Hsieh P-H, Ueng SWN (2013) Gentamicin in bone cement: a potentially more effective prophylactic measure of infectionin joint arthroplasty. Bone Joint Res 2:220–226

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Seghrouchni K, van Delden C, Dominguez D et al (2012) Remission after treatment of osteoarticular infections due to Pseudomonas aeruginosa versus Staphylococcus aureus: a case-controlled study. Int Orthop 36:1065–1071

    Article  PubMed Central  PubMed  Google Scholar 

  5. Schmidmaier G, Lucke M, Wildemann B et al (2006) Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review. Injury 37(Suppl 2):S105–S112

    Article  PubMed  Google Scholar 

  6. Lew DP, Waldvogel FA (2004) Osteomyelitis. Lancet 364:369–379

    Article  CAS  PubMed  Google Scholar 

  7. Rod-Fleury T, Dunkel N, Assal M et al (2011) Duration of post-surgical antibiotic therapy for adult chronic osteomyelitis: a single-centre experience. Int Orthop 35:1725–1731

    Article  PubMed Central  PubMed  Google Scholar 

  8. Betz M, Abrassart S, Vaudaux P et al (2014) Increased risk of joint failure in hip prostheses infected with Staphylococcus aureus treated with debridement, antibiotics and implant retention compared to Streptococcus. Int Orthop. doi:10.1007/s00264-014-2510-z

    Google Scholar 

  9. Antoci V, Adams CS, Parvizi J et al (2008) The inhibition of Staphylococcus epidermidis biofilm formation by vancomycin-modified titanium alloy and implications for the treatment of periprosthetic infection. Biomaterials 29:4684–4690

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Joosten U, Joist A, Gosheger G et al (2005) Effectiveness of hydroxyapatite-vancomycin bone cement in the treatment of Staphylococcus aureus induced chronic osteomyelitis. Biomaterials 26:5251–5258

    Article  CAS  PubMed  Google Scholar 

  11. Dion A, Langman M, Hall G, Filiaggi M (2005) Vancomycin release behaviour from amorphous calcium polyphosphate matrices intended for osteomyelitis treatment. Biomaterials 26:7276–7285

    Article  CAS  PubMed  Google Scholar 

  12. Kittinger C, Marth E, Windhager R et al (2011) Antimicrobial activity of gentamicin palmitate against high concentrations of Staphylococcus aureus. J Mater Sci Mater Med 22:1447–1453

    Article  CAS  PubMed  Google Scholar 

  13. Gracia E, Laclériga A, Monzón M et al (1998) Application of a rat osteomyelitis model to compare in vivo and in vitro the antibiotic efficacy against bacteria with high capacity to form biofilms. J Surg Res 79:146–153

    Article  CAS  PubMed  Google Scholar 

  14. Ozturk AM, Tabak AY, Aktekin CN et al (2008) Alendronate enhances antibiotic-impregnated bone grafts in the treatment of osteomyelitis. Int Orthop 32:821–827

    Article  PubMed Central  PubMed  Google Scholar 

  15. Fassbender M, Minkwitz S, Kronbach Z et al (2013) Local gentamicin application does not interfere with bone healing in a rat model. Bone 55:298–304

    Article  CAS  PubMed  Google Scholar 

  16. Matl FD, Obermeier A, Repmann S et al (2008) New anti-infective coatings of medical implants. Antimicrob Agents Chemother 52:1957–1963

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Lucke M, Schmidmaier G, Sadoni S et al (2003) A new model of implant-related osteomyelitis in rats. J Biomed Mater Res B Appl Biomater 67:593–602

    Article  CAS  PubMed  Google Scholar 

  18. Vogt S, Kühn K-D, Gopp U, Schnabelrauch M (2005) Resorbable antibiotic coatings for bone substitutes and implantable devices. Materwiss Werksttech 36:814–819

    Article  CAS  Google Scholar 

  19. Heller DN, Peggins JO, Nochetto CB et al (2005) LC/MS/MS measurement of gentamicin in bovine plasma, urine, milk, and biopsy samples taken from kidneys of standing animals. J Chromatogr B Anal Technol Biomed Life Sci 821:22–30

    Article  CAS  Google Scholar 

  20. Cowan ST, Shaw C, Williams RE (1954) Type strain for Staphylococcus aureus Rosenbach. J Gen Microbiol 10:174–176

    Article  CAS  PubMed  Google Scholar 

  21. Giffen PS, Turton J, Andrews CM et al (2003) Markers of experimental acute inflammation in the wistar han rat with particular reference to haptoglobin and C-reactive protein. Arch Toxicol 77:392–402

    Article  CAS  PubMed  Google Scholar 

  22. Welch JM, Weaver CM, Turner CH (2004) Adaptations to free-fall impact are different in the shafts and bone ends of rat forelimbs. J Appl Physiol 97:1859–1865

    Article  CAS  PubMed  Google Scholar 

  23. Gristina AG (1987) Biomaterial-centered infection: microbial adhesion versus tissue integration. Science 237:1588–1595

    Article  CAS  PubMed  Google Scholar 

  24. Lewis CS, Supronowicz PR, Zhukauskas RM et al (2012) Local antibiotic delivery with demineralized bone matrix. Cell Tissue Bank 13:119–127

    Article  CAS  PubMed  Google Scholar 

  25. Hanssen AD (2005) Local antibiotic delivery vehicles in the treatment of musculoskeletal infection. Clin Orthop Relat Res 437:91–96

    Article  PubMed  Google Scholar 

  26. Lucke M, Schmidmaier G, Sadoni S et al (2003) Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats. Bone 32:521–531

    Article  CAS  PubMed  Google Scholar 

  27. Lewis CS, Katz J, Baker MI et al (2011) Local antibiotic delivery with bovine cancellous chips. J Biomater Appl 26:491–506

    Article  CAS  PubMed  Google Scholar 

  28. Joosten U, Joist A, Frebel T et al (2004) Evaluation of an in situ setting injectable calcium phosphate as a new carrier material for gentamicin in the treatment of chronic osteomyelitis: studies in vitro and in vivo. Biomaterials 25:4287–4295

    Article  CAS  PubMed  Google Scholar 

  29. Cornell CN, Tyndall D, Waller S et al (1993) Treatment of experimental osteomyelitis with antibiotic-impregnated bone graft substitute. J Orthop Res 11:619–626

    Article  CAS  PubMed  Google Scholar 

  30. Hamanishi C, Kitamoto K, Tanaka S et al (1996) A self-setting TTCP-DCPD apatite cement for release of vancomycin. J Biomed Mater Res 33:139–143

    Article  CAS  PubMed  Google Scholar 

  31. Lucke M, Wildemann B, Sadoni S et al (2005) Systemic versus local application of gentamicin in prophylaxis of implant-related osteomyelitis in a rat model. Bone 36:770–778

    Article  CAS  PubMed  Google Scholar 

  32. Helbig L, Simank HG, Lorenz H et al (2014) Establishment of a new methicillin resistant Staphylococcus aureus animal model of osteomyelitis. Int Orthop 38:891–897

    Article  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

The present study was supported by Synthes GmbH, Umkirch, Germany. The authors thank Mr. Guido Schemken and his staff at the Central Animal Housing Facility in Marburg, as well as Prof. Dr. Markus Schofer and Dr. Stefan Lakemeier for their kind support in performing this study.

Conflict of interest

All authors declare that there is no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Orthopaedics and Rheumatology, University Hospital Marburg, Marburg, Germany

    Christian Fölsch, Maike Federmann, Susanne Fuchs-Winkelmann, Jürgen R. J. Paletta & Philip P. Roessler

  2. Department of Orthopaedics and Traumatology, University Hospital Bonn, Sigmund-Freud-Str. 25, 53127, Bonn, Germany

    Philip P. Roessler

  3. Department of Orthopaedics and Orthopaedic Surgery, Medical University of Graz, Graz, Austria

    Klaus D. Kuehn & Stefan Kogler

  4. Institute of Hygiene, Microbiology and Environmental Medicine, Medical University of Graz, Graz, Austria

    Clemens Kittinger & Gernot Zarfel

  5. Institute of Medical Microbiology and Hygiene, Philipps-University Marburg, Marburg, Germany

    Martina Kerwat

  6. Department of Diagnostic and Interventional Radiology, University Hospital Marburg, Marburg, Germany

    Steve Braun

Authors
  1. Christian Fölsch
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  2. Maike Federmann
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  3. Klaus D. Kuehn
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  4. Clemens Kittinger
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  5. Stefan Kogler
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  7. Martina Kerwat
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  8. Steve Braun
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  9. Susanne Fuchs-Winkelmann
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  10. Jürgen R. J. Paletta
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  11. Philip P. Roessler
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Correspondence to Philip P. Roessler.

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Fölsch, C., Federmann, M., Kuehn, K.D. et al. Coating with a novel gentamicinpalmitate formulation prevents implant-associated osteomyelitis induced by methicillin-susceptible Staphylococcus aureus in a rat model. International Orthopaedics (SICOT) 39, 981–988 (2015). https://doi.org/10.1007/s00264-014-2582-9

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  • DOI: https://doi.org/10.1007/s00264-014-2582-9

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