A review of local antibiotic implants and applications to veterinary orthopaedic surgery

G. Hayes; N. Moens; T. Gibson

doi:10.3415/VCOT-12-05-0065

Veterinary and Comparative Orthopaedics and Traumatology, Table of Contents

Vet Comp Orthop Traumatol 2013; 26(04): 251-259
DOI: 10.3415/VCOT-12-05-0065

Review Article

Schattauer GmbH

A review of local antibiotic implants and applications to veterinary orthopaedic surgery

G. Hayes

¹University of Guelph, Department of Clinical Studies, Guelph, Ontario, Canada

,

N. Moens

¹University of Guelph, Department of Clinical Studies, Guelph, Ontario, Canada

,

T. Gibson

¹University of Guelph, Department of Clinical Studies, Guelph, Ontario, Canada

› Author Affiliations

Abstract

Summary

In the face of increasing incidence of multidrug resistant implant infections, local antibiotic modalities are receiving increased attention for both infection prophylaxis and treatment. Local antibiotic therapy that achieves very high antibiotic drug concentrations at the site of the implant may represent an avenue for treatment of biofilmforming bacterial pathogens. Randomized controlled trials in human patients have demonstrated an infection risk reduction when antibiotic-impregnated cement is used for infection prophylaxis in implanted joint prostheses, and when a gentamicin-impregnated collagen sponge is used for infection prophylaxis in midline sternotomy. The other modalities discussed have for the most part yet to be evaluated in randomized controlled trials in veterinary or human patients. In general, the in vivo pharmacokinetics and appropriate dosing profiles for local antibiotic modalities have yet to be elucidated. Toxicity is possible, and attention to the dose applied is warranted.

Keywords

Antibiotics - implant - infection - local antibiotic delivery

Full Text

References

References
1 Mangram AJ, Horan TC, Pearson ML. et al. Guideline for prevention of surgical site infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control 1999; 27: 97-132.
2 Weese JS. A review of post-operative infections in veterinary orthopaedic surgery. Vet Comp Orthop Traumatol 2008; 21: 99-105.
3 Barie P, Eachempati S. Surgical site infections. Surg Clin North Am 2005; 85: 1115-1135.
4 Kona-Boun J, Silim A, Troncy E. Immunologic aspects of veterinary anesthesia and analgesia. J Am Vet Med Assoc 2005; 226: 355-363.
5 Prittie JE. Controversies related to red blood cell transfusion in critically ill patients. J Vet Emerg Crit Care 2010; 20: 167-176.
6 Booth DM. Interpreting culture and susceptibility data in critical care: perks and pitfalls. J Vet Emerg Crit Care 2010; 20: 110-131.
7 Diefenbeck M, Muckley T, Hofmann G. Prophylaxis and treatment of implant-related infections by local application of antibiotics. Injury 2006; 37: S95-S104.
8 Perrenten V, Kadlec K, Schwarz S. et al. Clonal spread of methicillin-resistant staphylococcus pseudintermedius in Europe and North America: an international multi-centre study. J Antimicrob Chemo 2010; 65: 1145-1154.
9 Cohn LA, Middleton JR. A veterinary perspective on methicillin resistant staphylococci. J Vet Emerg Crit Care 2010; 20: 31-45.
10 Gristina A. Biomaterial- centered infection: microbial adhesion versus tissue integration. Clin Orthop Relat Res 2004; 427: 4-12.
11 Clements DN, Owen MR, Mosley JR. et al. Retrospective study of bacterial infective arthritis in 31 dogs. J Small Anim Pract 2005; 46: 171-176.
12 Del Pozo JL, Patel R. Infection associated with prosthetic joints. N Engl J Med 2009; 361: 787-794.
13 Hetrick EM, Schoenfisch MH. Reducing implant-related infections: active release strategies. Chem Soc Rev 2006; 35: 780-789.
14 Cargill J, Upton M. Low concentrations of vancomycin stimulate biofilm formation in some clinical isolates of Staphylococcus epidermis. J Clin Pathol 2009; 62: 1112-1116.
15 Harris L, Richards R. Staphylococci and implant surfaces: a review. Injury 2006; 37: S3-14.
16 Gibson J, Morton J, Cobbold R. et al. Multidrug resistant E. coli and enterobacter extraintestinal infection in 37 dogs. J Vet Intern Med 2008; 22: 844-850.
17 Clinical and Laboratory Standards Institute. Performance Standards for Antimicrobial Disk and Dilution Susceptibility Tests for Bacteria Isolated From Animals; Approved Standard-Third Edition. CLSI M31-A3 Wayne (PA, USA): 2008
18 Schroder A, Kland R, Peschel A. et al. Live cell imaging of phagosome maturation in Staphylococcus aureus infected human endothelial cells: small colony variants are able to survive in lysosomes. Med Microbiol Immunol 2006; 195: 185-194.
19 Westropp JL, Sykes JE, Irom S. et al. Evaluation of the efficacy and safety of high dose short duration enrofloxacin treatment regimen for uncomplicated UTI in dogs. J Vet Intern Med 2012; 26: 506-512.
20 Sandberg T, Skoog G, Hermansson A. Ciprofloxacin for 7 days versus 14 days in women with acute pyelonephritis: a randomised, open label and double blind placebo controlled non-inferiority trial. Lancet 2012; 380: 484-490.
21 Roblot F, Besnier JM, Juhel L. Optimal duration of antibiotic therapy in vertebral osteomyelitis. Semin Arthritis Rheum 2007; 36: 269-277.
22 Cockshut JR. Chapter 6 - Bone infection. In: Sumner-Smith G, editor. Bone in Clinical Orthopaedics. New York: AO Publishing; 2002; p. 2002-205.
23 Li XZ, Nikaido H. Efflux mediated drug resistance in bacteria. Drugs 2004; 64: 159-204.
24 Chambers HF. General Considerations of Antimicrobial Therapy. In: Brunton L, Lazo JS, Parker KL. editors. Goodman Gilman’s The Pharmacological Basis of Therapeutics. McGraw-Hill Companies; 2006. p. 2006-1095.
25 Landersdorfer CB, Bulitta JB, Kinzig M. Penetration of antibacterials into bone. Clin Pharmacokinet 2009; 48: 89-124.
26 Darley ES, MacGowan AP. Antibiotic treatment of gram positive bone and joint infections. J Antimicrob Chemo 2004; 53: 928-935.
27 Hooper DC. Mechanisms of fluoroquinolone resistance. Drug Resist Updat 1999; 2: 38-55.
28 Rathbone CR, Cross JD, Brown KV. et al. Effect of various concentrations of antibiotics on osteogenic cell viability and activity. J Orthop Res 2011; 29: 1070-1074.
29 Anagnostakos K, Hitzler P, Pape D. et al. Persistence of bacterial growth on antibiotic-loaded beads: is it actually a problem?. Acta Orthop 2008; 79: 302-307.
30 Beraud R, Huneault L, Bernier D. Comparison of the selection of antimicrobial resistance in fecal E.coli during enrofloxacin administration with local drug delivery system or with intramuscular injections. Can J Vet Res 2008; 72: 311-319.
31 Wininger DA, Fass RJ. Antibiotic-impregnated cement and beads for orthopedic infections. Antimicrob Agents Chemother 1996; 40: 2675-2679.
32 Ethell M, Bennet R, Brown M. et al. In vitro elution of gentamicin, amikacin, and ceftiofur from polymethylmethacrylate and hydroxyapatite cement. Vet Surg 2000; 29: 375-382.
33 Atilla A, Boothe M, Tollett M. et al. In vitro elution of amikacin and vancomycin from impregnated plaster of paris beads. Vet Surg 2010; 39: 715-721.
34 Phillips H, Boothe D, Shofer F. et al. In vitro elution studies of amikacin and cefazolin from polymethylmethacrylate. Vet Surg 2007; 36: 272-278.
35 Ramos J, Howard R, Pleasant R. et al. Elution of metronidazole and gentamicin from polymethymethacrylate beads. Vet Surg 2003; 32: 251-261.
36 Baez L, Langston S, Givaruangsawat S. et al. Evaluation of in vitro serial antibiotic elution from meropenem-impregnated polymethylmethacrylate beads after ethylene oxide gas and autoclave sterilization. Vet Comp Ortho Traumatol 2011; 24: 39-44.
37 Garvin K, Miyano J, Robinson D. et al. Polylactide/ polyglycolide antibiotic implants in the treatment of osteomyelitis, a canine model. J Bone Joint Surg 1994; 76: 1500-1506.
38 Calhoun JH, Henry SL, Anger DM. et al. The treatment of infected nonunions with gentamicin-polymethyl- methacrylate antibiotic beads. Clin Orthop 1993; 295: 23-27.
39 Blaha JD, Calhoun JH, Nelson CL. et al. Comparison of the clinical efficacy and tolerance of gentamicin PMMA beads on surgical wire versus combined and systemic therapy for osteomyelitis. Clinical Orthop Rel Res 1993; 295: 8-12.
40 Albuhairan B, Hind D, Hutchinson A. Antibiotic prophylaxis for wound infections in total joint arthroplasty, a systematic review. J Bone Joint Surg Br 2008; 90: 915-919.
41 Weisman D, Olmstead M, Kowalski J. et al. In vitro evaluation of antibiotic elution from PMMA and mechanical assessment of antibiotic-PMMA composites. Vet Surg 2000; 29: 245-251.
42 Lewis G. Properties of antibiotic-loaded bone cement for use in cemented arthroplasties: a state-of-the-art review. J Biomed Mater Res B Appl Biomater 2009; 89: 558-574.
43 Ostermann PA, Seligson D, Henry SL. Local antibiotic therapy for severe open fractures. A review of 1085 cases. J Bone Joint Surg Br 1995; 77: 93-97.
44 Neut D, van de, Belt H, van Horn JR. et al. Residual gentamicin release from antibiotic loaded PMMA beads 5 years after implantation. Biomaterials 2003; 24: 1829-1831.
45 Lapid O. Use of gentamicin collagen sponges for the treatment of periprosthetic breast implant infection. J Plast Recostr Aesthet Surg 2011; 64: 313-316.
46 Swieringa AJ, Goosen J, Jansman F. In vivo pharmacokinetics of a gentamicin-loaded collagen sponge in acute peri-prosthetic infection: serum values in 19 patients. Acta Orthopaedica 2008; 79: 637-642.
47 Griffis C, Metcalfe F, Bowling F. et al. The use of gentamicin-impregnated foam in the management of diabetic foot infections: a promising delivery system?. Expert Opin Drug Deliv 2009; 6: 639-642.
48 Andersson RE, Lukas G, Skullman S. et al. Local administration of antibiotics by gentamicin-collagen sponge does not improve wound healing or reduce recurrence rate after pilonidal excision with primary suture: a prospective, randomized, controlled trial. World J Surg 2010; 34: 3042-3048.
49 Gustafsson UM, Graf W. Randomized clinical trial of local gentamicin-collagen treatment in advancement flap repair for anal fistula. Br J Surg 2006; 93: 1202-1207.
50 Nowacki MP, Rutkowski A, Oledzki J. Prospective, randomized trial examining the role of gentamicin-containing collagen sponge in the reduction of postoperative morbidity in rectal cancer patients: early results and surprising outcome at 3-year follow-up. Int J Colorectal Dis 2005; 20: 114-120.
51 Chaudhary S, Sen RK, Sini UC. et al. Use of gentamicin-loaded collagen sponge in internal fixation of open fractures. Chin J Traumatol 2011; 14: 209-214.
52 Friberg O, Svedjeholm R, Soderquist B. et al. Local gentamicin reduces sternal wound infections after cardiac surgery: a randomized controlled trial. Ann Thorac Surg 2005; 79: 153-162.
53 Renwick AI, Dennis R, Gemmill T. Treatment of lumbosacral discospondylitis by surgical stabilization and application of a gentamicin impregnated collagen sponge. Vet Comp Orthop Traumatol 2010; 23: 266-272.
54 Owen M, Moores AP, Coe RJ. Management of MRSA septic arthritis in a dog using a gentamicin impregnated collagen sponge. J Small Anim Pract 2004; 45: 609-612.
55 Haerdi-Landerer MC, Habermacher J, Wenger B. et al. Slow release antibiotics for treatment of septic arthritis in large animals. Vet J 2010; 184: 14-20.
56 Schimmer C, Ozkur M, Sinha B. Gentamicin-collagen sponge reduces sternal wound complications after heart surgery: a controlled, prospectively randomised, double-blind study. J Thorac Cardiovasc Surg 2012; 143: 194-200.
57 Bennett-Guerrero E, Pappas T, Koltun W. et al. Gentamicin-collagen sponge for infection prophylaxis in colo-rectal surgery. New Eng J Med 2010; 363: 1038-1049.
58 Ivester K, Adams S, Moore G. et al. Gentamicin concentrations in synovial fluid obtained from the tarsocrural joints of horses after implantation of gentamicin-impregnated collagen sponges. Am J Vet Res 2006; 67: 1519-1526.
59 Hayes G, Gibson T, Moens N. et al. Intra-articular pharmacokinetics of a gentamicin impregnated collagen sponge-boom and bust. Vet Surg. 2013 in press.
60 Mehta S, Humprey JS, Schenkman D. et al. Gentamicin distribution from a collagen carrier. J Orthop Res 1996; 14: 749-754.
61 Kilian O, Hossain H, Flesch I. et al. Elution kinetics, antimicrobial efficacy, and degradation and microvasculature of a new gentamicin-loaded collagen fleece. J Biomed Mater Res Part B Appl Biomater 2009; 90: 210-222.
62 Hayes G, Gibson T, Moens N. Safety assessment of a gentamicin impregnated collagen sponge (GICS) placed in the canine stifle joint: effect on joint inflammation and renal function. J Bone Joint Surg. 2013 in press.
63 Swieringa A, Tulp N. Toxic serum gentamicin levels after the use of gentamicin loaded collagen sponges in infected total hip arthroplasty. Acta Orthopaedica 2005; 76: 75-77.
64 Delfosse V, El Warak A, Clerfond P. et al. Clinical investigation of local implantation of gentamicin impregnated collagen sponges in dogs. Can Vet J 2011; 52: 627-630.
65 Thomas LA, Bizikova T, Minihan AC. et al. In vitro elution and anti-bacterial activity of clindamicin, amikacin, and vancomycin for R-gel polymer. Vet Surg 2011; 40: 774-780.
66 Lewis CS, Supronowicz PR, Zhukauskas RM. et al. Local antibiotic delivery with demineralized bone matrix. Cell Tissue Bank 2012; 13: 119-127.
67 Beardmore AA, Brookes DE, Wenke JC. Effectiveness of local antibiotic delivery with an osteoinductive and osteoconductive bone-graft substitute. J Bone Joint Surg Am 2005; 87: 107-112.
68 Perren S, Mathys R, Pohler O. Implants and materials in fracture fixation. In: Johnson A, Houlton J, Vannini R. editors. AO Principles of Fracture Management in the Dog and Cat. New York: Thieme; 2005. p. 2005-221.
69 Marcellin-Little D, Sutherland B, Harryson O. et al. In vitro evaluation of free-form biodegradable bone. Am J Vet Res 2010; 71: 1508-1515.
70 Salkku-Backstrom Ralha J, Vaalma T. Repair of radial fractures in toy breed dogs with self-reinforced biodegradable bone plates, metal screws, and light-weight external coaptation. Vet Surg 2005; 34: 11-17.
71 Arens S, Schlegel U, Printzen G. et al. Influence of materials for fixation implants on local infection. An experimental study of steel versus titanium DCP in rabbits. J Bone Joint Surg Br 1996; 78: 647-651.
72 Johansson A, Lindgren JU, Nord CE. et al. Material and design in haematogenous implant-associated infections in a rabbit model. Injury 1999; 30: 651-657.
73 Pieske O, Geleng P, Zaspel J. et al. Titanium alloy pins versus stainless steel pins in external fixation at the wrist: a randomized prospective study. J Trauma 2008; 64: 1275-1280.
74 Sheehan E, Mckenna J, Mulhall K. Adhesion of staphylococcus to orthopaedic metals, an in vivo study. J Orthop Res 2004; 22: 39-43.
75 Schaer T, Stewart S, Hsu B. et al. Hydrophobic polycationic coatings that inhibit biofilms and support bone healing during infections. Biomat 2012; 33: 1245-1254.
76 Lucke M, Schmidmaier G, Sadoni S. et al. Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats. Bone 2003; 32: 521-531.
77 Schmidmaler G, Lucke M, Wildemanne B. et al. Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review. Injury 2006; 37: S105-112.
78 Fuchs T, Stange R, Schmidmaler G. The use of gentamicin coated nails in the tibia: preliminary results of a prospective study. Arch Orthop Trauma Surg 2011; 131: 1419-1425.
79 Forster H, Marotta J, Heseltine K. et al. Bactericidal activity of antimicrobial coated polyurethane sleeves for external fixation pins. J Orthop Res 2004; 22: 671-677.
80 Holt J, Hertzberg B, Weinhold P. et al. Decreasing bacterial colonization of external fixation pins through nitric oxide release coatings. J Orthop Trauma 2011; 25: 432-437.
81 Hickok NJ, Shapiro IM. Immobilized antibiotics to prevent orthopaedic implant infections. Adv Drug Deliv Rev 2012; 64: 1165-1176.
82 Lara HH, Garza-Trevino EN, Turrent LI. et al. Silver nanoparticles are broad-spectrum bactericidal and virucidal compounds. J Nanobiotechnology. 2011 9. 30.
83 Sütterlin S, Tano Bergsten. et al. Effects of silver-based wound dressings on the bacterial flora in chronic leg ulcers and its susceptibility In vitro to silver. Acta Derm Venereol. 2012; 92: 34-9.
84 Ionita D, Grecu M, Ungureanu C, Demetrescu I. Antimicrobial activity of the surface coatings on TiAlZr implant biomaterial. J Bioscience Bioengineering 2011; 112: 630-634.
85 Fiedler J, Kolitsch A, Kleffner B. et al. Copper and silver ion implantation of aluminium oxide-blasted titanium surfaces: proliferative response of osteoblasts and antibacterial effects. Int J Artif Organs 2011; 34: 882-888.
86 Masse A, Bruno A, Bosetti M. et al. Prevention of pin track infection in external fixation with silver coated pins: clinical and microbiological results. J Biomed Mater Res 2000; 53: 600-604.
87 Hardes J, Von Eiff C, Streitbuerger A. et al. Reduction of periprosthetic infection with silver-coated megaprostheses in patients with bone sarcoma. J Surg Onc 2010; 101: 389-395.
88 Adams K, Couch L, Cierny G. et al. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Ortho Rel Res 1992; 278: 244-248.
89 Udomkusonsri P, Kaewmokul S, Arthitvong S. et al. Elution profile of cefazolin from PMMA beads. J Vet Med Sci 2012; 74: 301-305.
90 Anagnostakos K, Wilmes P, Schmitt P. et al. Elution of gentamicin and vancomycin from PMMA beads and hip spacers in vivo. Acta orthopaedica 2009; 80: 193-197.