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Published in: Journal of Orthopaedic Science 1/2013

01-01-2013 | Original Article

The use of tissue sealants to deliver antibiotics to an orthopaedic surgical site with a titanium implant

Authors: Johanne D. Cashman, John K. Jackson, Clement Mugabe, Samuel Gilchrist, Kate Ball, Stephen Tredwell, Helen M. Burt

Published in: Journal of Orthopaedic Science | Issue 1/2013

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Abstract

Background

Orthopaedic surgery is associated with unacceptable infection rates that respond poorly to systemic antibiotics. The objective of this study was to use an animal model for orthopaedic implant infection to examine the ability of a new-generation fibrin tissue sealant to effectively deliver antibiotics to the surgical site.

Methods

The antibiotics cefazolin, fusidic acid or 5-fluorouracil were blended into Vitagel™ tissue sealant. The release rate of the drugs was measured using HPLC methods and bioactivity was measured by the zone of inhibition method with pathogenic Staphylococcus aureus. The antibiotic activity of the drug-loaded sealant was then tested in rats using infected orthopaedic surgical sites (titanium clip on spine). Efficacy was evaluated by residual bacterial counts on clips, clinical observations of infection, and histological findings.

Results

The drugs were released in a controlled manner over 2–4 days. All three antibiotics demonstrated strong antibacterial activity when released from the sealants. None of the treated animals demonstrated systemic illness. Post mortem dissection revealed a well-encapsulated abscess surrounding the titanium clip with erosion of the bony process. Using an inoculum of 1–5 × 103 CFU, treatment with antibiotic-loaded fibrin sealant demonstrated reduced infective swelling and reduced bacterial counts on surgical clip swabs compared to control rats or rats treated with antibiotic only. This model allowed for almost 100 % infectivity with a 0 % mortality rate due to infection, mimicking the clinical features of human implant infection.

Conclusion

The results support the use of antibiotic-loaded commercially available fibrin sealants to prevent infection after implant surgery.
Literature
1.
go back to reference Marrie TJ, Costerton JW. Mode of growth of bacterial pathogens in chronic polymicrobial human osteomyelitis. J Clin Microbiol. 1985;22:924–33.PubMed Marrie TJ, Costerton JW. Mode of growth of bacterial pathogens in chronic polymicrobial human osteomyelitis. J Clin Microbiol. 1985;22:924–33.PubMed
2.
go back to reference Petty W, Spanier S, Shuster JJ, Silverthorne C. The influence of skeletal implants on incidence of infection. Experiments in a canine model. J Bone Joint Surg Am. 1985;67:1236–44.PubMed Petty W, Spanier S, Shuster JJ, Silverthorne C. The influence of skeletal implants on incidence of infection. Experiments in a canine model. J Bone Joint Surg Am. 1985;67:1236–44.PubMed
3.
go back to reference Trampuz A, Zimmerli W. Antimicrobial agents in orthopaedic surgery: prophylaxis and treatment. Drugs. 2006;66:1089–105.PubMedCrossRef Trampuz A, Zimmerli W. Antimicrobial agents in orthopaedic surgery: prophylaxis and treatment. Drugs. 2006;66:1089–105.PubMedCrossRef
4.
go back to reference Fujimoto K, Yamamura K, Osada T, Hayashi T, Nabeshima T, Matsushita M, Nishikimi N, Sakurai T, Nimura Y. Subcutaneous tissue distribution of vancomycin from a fibrin glue/Dacron graft carrier. J Biomed Mater Res. 1997;36:564–7.PubMedCrossRef Fujimoto K, Yamamura K, Osada T, Hayashi T, Nabeshima T, Matsushita M, Nishikimi N, Sakurai T, Nimura Y. Subcutaneous tissue distribution of vancomycin from a fibrin glue/Dacron graft carrier. J Biomed Mater Res. 1997;36:564–7.PubMedCrossRef
5.
go back to reference Nishimoto K, Yamamura K, Fukase F, Kobayashi M, Nishikimi N, Komori K. Subcutaneous tissue release of amikacin from a fibrin glue/polyurethane graft. J Infect Chemother. 2004;10:101–4.PubMedCrossRef Nishimoto K, Yamamura K, Fukase F, Kobayashi M, Nishikimi N, Komori K. Subcutaneous tissue release of amikacin from a fibrin glue/polyurethane graft. J Infect Chemother. 2004;10:101–4.PubMedCrossRef
6.
go back to reference Ueng SW, Yuan LJ, Lee N, Lin SS, Chan EC, Weng JH. In vivo study of biodegradable alginate antibiotic beads in rabbits. J Orthop Res. 2004;22:592–9.PubMedCrossRef Ueng SW, Yuan LJ, Lee N, Lin SS, Chan EC, Weng JH. In vivo study of biodegradable alginate antibiotic beads in rabbits. J Orthop Res. 2004;22:592–9.PubMedCrossRef
7.
go back to reference Schlag G, Redl H. Fibrin sealant in orthopaedic surgery. Clin Orthop Relat Res. 1988;227:269–85.PubMed Schlag G, Redl H. Fibrin sealant in orthopaedic surgery. Clin Orthop Relat Res. 1988;227:269–85.PubMed
8.
go back to reference Spotnitz WD, Prabhu R. Fibrin sealant tissue adhesive—review and update. J Long Term Eff Med Implants. 2005;15:245–70.PubMedCrossRef Spotnitz WD, Prabhu R. Fibrin sealant tissue adhesive—review and update. J Long Term Eff Med Implants. 2005;15:245–70.PubMedCrossRef
9.
go back to reference Shireman PK, Greisler HP. Fibrin sealant in vascular surgery: a review. J Long Term Eff Med Implants. 1998;8:117–32.PubMed Shireman PK, Greisler HP. Fibrin sealant in vascular surgery: a review. J Long Term Eff Med Implants. 1998;8:117–32.PubMed
10.
go back to reference Mader JT, Stevens CM, Stevens JH, Ruble R, Lathrop JT, Calhoun JH. Treatment of experimental osteomyelitis with a fibrin sealant antibiotic implant. Clin Orthop Relat Res. 2002:58–72. Mader JT, Stevens CM, Stevens JH, Ruble R, Lathrop JT, Calhoun JH. Treatment of experimental osteomyelitis with a fibrin sealant antibiotic implant. Clin Orthop Relat Res. 2002:58–72.
11.
go back to reference Tredwell S, Jackson JK, Hamilton D, Lee V, Burt HM. Use of fibrin sealants for the localized, controlled release of cefazolin. Can J Surg. 2006;49:347–52.PubMed Tredwell S, Jackson JK, Hamilton D, Lee V, Burt HM. Use of fibrin sealants for the localized, controlled release of cefazolin. Can J Surg. 2006;49:347–52.PubMed
12.
go back to reference Woolverton CJ, Huebert K, Burkhart B, MacPhee M. Subverting bacterial resistance using high dose, low solubility antibiotics in fibrin. Infection. 1999;27:28–33.PubMedCrossRef Woolverton CJ, Huebert K, Burkhart B, MacPhee M. Subverting bacterial resistance using high dose, low solubility antibiotics in fibrin. Infection. 1999;27:28–33.PubMedCrossRef
13.
go back to reference Poelstra KA, Barekzi NA, Grainger DW, Gristina AG, Schuler TC. A novel spinal implant infection model in rabbits. Spine (Phila Pa 1976). 2000;25:406–10. Poelstra KA, Barekzi NA, Grainger DW, Gristina AG, Schuler TC. A novel spinal implant infection model in rabbits. Spine (Phila Pa 1976). 2000;25:406–10.
14.
go back to reference Stall AC, Becker E, Ludwig SC, Gelb D, Poelstra KA. Reduction of postoperative spinal implant infection using gentamicin microspheres. Spine (Phila Pa 1976). 2009;34:479–83. Stall AC, Becker E, Ludwig SC, Gelb D, Poelstra KA. Reduction of postoperative spinal implant infection using gentamicin microspheres. Spine (Phila Pa 1976). 2009;34:479–83.
15.
go back to reference Fluckiger U, Ulrich M, Steinhuber A, Doring G, Mack D, Landmann R, Goerke C, Wolz C. Biofilm formation, icaADBC transcription, and polysaccharide intercellular adhesin synthesis by staphylococci in a device-related infection model. Infect Immun. 2005;73:1811–9.PubMedCrossRef Fluckiger U, Ulrich M, Steinhuber A, Doring G, Mack D, Landmann R, Goerke C, Wolz C. Biofilm formation, icaADBC transcription, and polysaccharide intercellular adhesin synthesis by staphylococci in a device-related infection model. Infect Immun. 2005;73:1811–9.PubMedCrossRef
16.
go back to reference Ney AL, Kelly PH, Tsukayama DT, Bubrick MP. Fibrin glue-antibiotic suspension in the prevention of prosthetic graft infection. J Trauma. 1990;30:1000–5; discussion 5–6. Ney AL, Kelly PH, Tsukayama DT, Bubrick MP. Fibrin glue-antibiotic suspension in the prevention of prosthetic graft infection. J Trauma. 1990;30:1000–5; discussion 5–6.
17.
go back to reference Woolverton CJ, Fulton JA, Salstrom SJ, Hayslip J, Haller NA, Wildroudt ML, MacPhee M. Tetracycline delivery from fibrin controls peritoneal infection without measurable systemic antibiotic. J Antimicrob Chemother. 2001;48:861–7.PubMedCrossRef Woolverton CJ, Fulton JA, Salstrom SJ, Hayslip J, Haller NA, Wildroudt ML, MacPhee M. Tetracycline delivery from fibrin controls peritoneal infection without measurable systemic antibiotic. J Antimicrob Chemother. 2001;48:861–7.PubMedCrossRef
18.
go back to reference Zilch H, Lambiris E. The sustained release of cefotaxim from a fibrin-cefotaxim compound in treatment of osteitis. Pharmacokinetic study and clinical results. Arch Orthop Trauma Surg. 1986;106:36–41.PubMedCrossRef Zilch H, Lambiris E. The sustained release of cefotaxim from a fibrin-cefotaxim compound in treatment of osteitis. Pharmacokinetic study and clinical results. Arch Orthop Trauma Surg. 1986;106:36–41.PubMedCrossRef
19.
go back to reference Craig WA, Ebert SC. Continuous infusion of beta-lactam antibiotics. Antimicrob Agents Chemother. 1992;36:2577–83.PubMedCrossRef Craig WA, Ebert SC. Continuous infusion of beta-lactam antibiotics. Antimicrob Agents Chemother. 1992;36:2577–83.PubMedCrossRef
20.
go back to reference Cavanaugh DL, Berry J, Yarboro SR, Dahners LE. Better prophylaxis against surgical site infection with local as well as systemic antibiotics. An in vivo study. J Bone Joint Surg Am. 2009;91:1907–12.PubMedCrossRef Cavanaugh DL, Berry J, Yarboro SR, Dahners LE. Better prophylaxis against surgical site infection with local as well as systemic antibiotics. An in vivo study. J Bone Joint Surg Am. 2009;91:1907–12.PubMedCrossRef
21.
go back to reference Zeller V, Durand F, Kitzis MD, Lhotellier L, Ziza JM, Mamoudy P, Desplaces N. Continuous cefazolin infusion to treat bone and joint infections: clinical efficacy, feasibility, safety, and serum and bone concentrations. Antimicrob Agents Chemother. 2009;53:883–7.PubMedCrossRef Zeller V, Durand F, Kitzis MD, Lhotellier L, Ziza JM, Mamoudy P, Desplaces N. Continuous cefazolin infusion to treat bone and joint infections: clinical efficacy, feasibility, safety, and serum and bone concentrations. Antimicrob Agents Chemother. 2009;53:883–7.PubMedCrossRef
22.
go back to reference An YH, Friedman RJ. Animal models of orthopaedic implant infection. J Invest Surg. 1998;11:139–46.PubMedCrossRef An YH, Friedman RJ. Animal models of orthopaedic implant infection. J Invest Surg. 1998;11:139–46.PubMedCrossRef
23.
go back to reference Melcher GA, Claudi B, Schlegel U, Perren SM, Printzen G, Munzinger J. Influence of type of medullary nail on the development of local infection. An experimental study of solid and slotted nails in rabbits. J Bone Joint Surg Br. 1994;76:955–9.PubMed Melcher GA, Claudi B, Schlegel U, Perren SM, Printzen G, Munzinger J. Influence of type of medullary nail on the development of local infection. An experimental study of solid and slotted nails in rabbits. J Bone Joint Surg Br. 1994;76:955–9.PubMed
24.
go back to reference Lucke M, Schmidmaier G, Sadoni S, Wildemann B, Schiller R, Stemberger A, Haas NP, Raschke M. A new model of implant-related osteomyelitis in rats. J Biomed Mater Res B Appl Biomater. 2003;67:593–602.PubMedCrossRef Lucke M, Schmidmaier G, Sadoni S, Wildemann B, Schiller R, Stemberger A, Haas NP, Raschke M. A new model of implant-related osteomyelitis in rats. J Biomed Mater Res B Appl Biomater. 2003;67:593–602.PubMedCrossRef
25.
go back to reference Monzon M, Garcia-Alvarez F, Lacleriga A, Gracia E, Leiva J, Oteiza C, Amorena B. A simple infection model using pre-colonized implants to reproduce rat chronic Staphylococcus aureus osteomyelitis and study antibiotic treatment. J Orthop Res. 2001;19:820–6.PubMedCrossRef Monzon M, Garcia-Alvarez F, Lacleriga A, Gracia E, Leiva J, Oteiza C, Amorena B. A simple infection model using pre-colonized implants to reproduce rat chronic Staphylococcus aureus osteomyelitis and study antibiotic treatment. J Orthop Res. 2001;19:820–6.PubMedCrossRef
26.
go back to reference Rissing JP, Buxton TB, Weinstein RS, Shockley RK. Model of experimental chronic osteomyelitis in rats. Infect Immun. 1985;47:581–6.PubMed Rissing JP, Buxton TB, Weinstein RS, Shockley RK. Model of experimental chronic osteomyelitis in rats. Infect Immun. 1985;47:581–6.PubMed
27.
go back to reference Johansson A, Svensson O, Blomgren G, Eliasson G, Nord CE. Anaerobic osteomyelitis. A new experimental rabbit model. Clin Orthop Relat Res;1991:297–301. Johansson A, Svensson O, Blomgren G, Eliasson G, Nord CE. Anaerobic osteomyelitis. A new experimental rabbit model. Clin Orthop Relat Res;1991:297–301.
28.
go back to reference Deysine M, Rosario E, Isenberg HD. Acute hematogenous osteomyelitis: an experimental model. Surgery. 1976;79:97–9.PubMed Deysine M, Rosario E, Isenberg HD. Acute hematogenous osteomyelitis: an experimental model. Surgery. 1976;79:97–9.PubMed
29.
go back to reference Mendel V, Simanowski HJ, Scholz HC, Heymann H. Therapy with gentamicin-PMMA beads, gentamicin-collagen sponge, and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in rats. Arch Orthop Trauma Surg. 2005;125:363–8.PubMedCrossRef Mendel V, Simanowski HJ, Scholz HC, Heymann H. Therapy with gentamicin-PMMA beads, gentamicin-collagen sponge, and cefazolin for experimental osteomyelitis due to Staphylococcus aureus in rats. Arch Orthop Trauma Surg. 2005;125:363–8.PubMedCrossRef
30.
go back to reference Waiz JM, Avelar RL, Longtine KJ, Carter KL, Mermel LA, Heard SO. Anti-infective external coating of central venous catheters: a randomized trail comparing 5-fluorouracil with chlorohexidene/silver sulfadiazine in preventing catheter colonization. Crit Care Med. 2010;38:2095–102.CrossRef Waiz JM, Avelar RL, Longtine KJ, Carter KL, Mermel LA, Heard SO. Anti-infective external coating of central venous catheters: a randomized trail comparing 5-fluorouracil with chlorohexidene/silver sulfadiazine in preventing catheter colonization. Crit Care Med. 2010;38:2095–102.CrossRef
31.
go back to reference Calhoun JH, Mader JT. Antibiotic beads in the management of surgical infections. Am J Surg. 1989;157:443–9.PubMedCrossRef Calhoun JH, Mader JT. Antibiotic beads in the management of surgical infections. Am J Surg. 1989;157:443–9.PubMedCrossRef
32.
go back to reference Penner MJ, Duncan CP, Masri BA. The in vitro elution characteristics of antibiotic-loaded CMW and Palacos-R bone cements. J Arthroplast. 1999;14:209–14.CrossRef Penner MJ, Duncan CP, Masri BA. The in vitro elution characteristics of antibiotic-loaded CMW and Palacos-R bone cements. J Arthroplast. 1999;14:209–14.CrossRef
Metadata
Title
The use of tissue sealants to deliver antibiotics to an orthopaedic surgical site with a titanium implant
Authors
Johanne D. Cashman
John K. Jackson
Clement Mugabe
Samuel Gilchrist
Kate Ball
Stephen Tredwell
Helen M. Burt
Publication date
01-01-2013
Publisher
Springer Japan
Published in
Journal of Orthopaedic Science / Issue 1/2013
Print ISSN: 0949-2658
Electronic ISSN: 1436-2023
DOI
https://doi.org/10.1007/s00776-012-0325-6

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