Skip to main content
SpringerLink
Log in

Local Antibacterial Therapy for the Management of Orthopaedic Infections

Pharmacokinetic Considerations

  • Review Article
  • Drug Delivery Systems
  • Published:
Clinical Pharmacokinetics Aims and scope Submit manuscript

Summary

Bone infection has long been a formidable foe of orthopaedic surgeons. The standard method of treating osteomyelitis generally consists of irrigation and debridement supplemented by pre- and postoperative antibiotics and intraoperative antimicrobial solutions. In the 1970s, Buchholz introduced the concept of local antibacterial therapy in the form of antibiotic impregnated bone cement to treated infected arthroplasties. From this, antibiotic impregnated beads were developed to treat local infections of bone and soft tissue. The advantage of these beads compared with parenteral therapy is that they deliver a high concentration of antibacterial locally while avoiding high systemic concentrations, thus avoiding adverse effects that are often associated with parenteral antibacterial therapy.

Additionally, methylmethacrylate bone cement does not significantly affect the immune response of the body. This makes the use of antibiotic-impregnated polymethylmethacrylate (PMMA) beads highly effective either as an alternative to, or in conjunction with, systemic antibiotic treatment of infected arthroplasties, and localised bone and soft tissue infection. This article explores the indications for the use of local therapy as well as any advantages or disadvantages it may have over systemic antibacterial treatment. Additionally, there are important pharmacokinetic considerations for the optimal use of antibacterial agents in the treatment of osteomyelitis.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Burri C. Post-traumatic osteomyelitis. Burn: Hans Huber, 1975: 11–7

    Google Scholar 

  2. Brady LP, Enneking WF, Franco JA. The effect of operating room environment on the infection rate after Charnley low-fraction total hip replacement. J Bone Joint Surg Am 1975; 57A: 80–3

    Google Scholar 

  3. Charnley J. The long-term results of low friction arthroplasty of the hip performed as primary intervention. J Bone Joint Surg Br 1972; 54B: 61–7

    Google Scholar 

  4. Coventry MB, Beckenbaugh RD, Nolan DR, et al. 2,021 total hip arthroplasties: a study of postoperative course and early complications. J Bone Joint Surg Am 1974; 56A: 273–84

    Google Scholar 

  5. Eftekhar N. Charnley ‘low-friction torque’ arthroplasty. Clin Orthop 1971; 81: 93–104

    Article  PubMed  CAS  Google Scholar 

  6. Nelson CE, Evarts CM, Andrish J, et al. Infected total hip replacement result and complications. In: Proceedings of the American Academy of Orthopaedic Surgeons. J Bone Joint Surg Am 1975; 57A: 1025

    Google Scholar 

  7. Salvati EA, Callaghan JJ, Brause BD, et al. Reimplantation in infection: elution of gentamicin from cement and beads. Clin Orthop 1986; 207: 83–93

    PubMed  Google Scholar 

  8. Buchholz HW, Engelbrecht E. Über die Depotwirkung einiger Antibiotika bei Vermischung mit dem Kunstharz Palacos. Chirurgie 1970; 41: 511–3

    CAS  Google Scholar 

  9. Danzinger LH. Controversies in antimicrobial therapy: innovative methods of administration. Am J Pharm 1986; 43: 650–2

    Google Scholar 

  10. Marr M, Alozozzibe G. Use of tobramycin bone cement. Drug Intell Clin Pharm 1984; 18: 883–4

    Google Scholar 

  11. Von Fraunhofer JA, Polk HC, Seligson D. Leaching of tobramycin from PMMA bone cement beads. J Biomed Mater Res 1985; 19: 751–6

    Article  Google Scholar 

  12. Harke A, Ritzerfeld W. The release of gentamicin into wound secretions from polymethylmethacrylate beads. Arch Orthop Trauma Surg 1979; 95: 65–70

    Article  Google Scholar 

  13. Klemm K. Treatment of chronic bone infection with gentamicin-PMMA chains and beads. Accid Surg 1976; 1 (Spec. Is.): 20

    Google Scholar 

  14. Goodell JA, Flick AB, Herbert JC, et al. Preparation and release characteristics of tobramycin-impregnated poly-methylmethacrylate beads. Am J Hosp Pharm 1986; 43: 1454–61

    PubMed  CAS  Google Scholar 

  15. Barton RPE, Moir AA. Use of a local gentamicin preparation (garamycin: chains) as prophylaxis against infection in major head or neck surgery: a pilot study. Pharmatherapeutica 1983; 3: 327–30

    PubMed  CAS  Google Scholar 

  16. Aubry DA, Jenkins NJ, Morgan WP, et al. The use of gentamicin-PMMA chains in abdominal surgery: a pilot study of prophylaxis against wound infection. Pharmatherapeutica 1986; 4: 536–40

    Google Scholar 

  17. Kupferburg A, Zer M, Rabinson S. The use of PMMA beads in recurrent high anal fistula: a preliminary report. World Surg 1984; 8: 970–4

    Article  Google Scholar 

  18. Spence RAJ, Anderson JR, Parks TG. The use of gentamicin-PMMA chains in colorectal surgery. Br J Clin Pract 1984; 38: 252–4

    PubMed  CAS  Google Scholar 

  19. VecSci V. Long term results in the treatment of septic bone and soft tissue diseases with gentamicin-PMMA chains and beads. In: Van Rens TJG, Kayser FH, editors. Local antibiotic treatment in osteomyelitis and soft tissue infections. International Congress Series. Amsterdam: Excerpta Medica, 1981; 556: 50–9

    Google Scholar 

  20. Josefsson G, Lindberg L, Wiklander B. Systemic antibiotics and gentamicin-containing bone cement in the prophylaxis of postoperative infections in total hip arthroplasty. Clin Orthop 1981; 159: 194–200

    PubMed  Google Scholar 

  21. Carlsson AS, Lidgren L, Lindberg L. Prophylactic antibiotics against early and late deep infections after total hip replacements. Acta Orthop Scand 1977; 48: 405

    Article  PubMed  CAS  Google Scholar 

  22. Trippel SB. Antibiotic-impregnated cement in total joint arthroplasty. J Bone Joint Surg Am 1986; 68A: 1297–302

    Google Scholar 

  23. Walenkamp GHIM. Gentamicin-PMMA beads: a clinical, phar-macokinetic, and topological study. Darmstadt: E. Merck, 1983

    Google Scholar 

  24. Seligson, D. Anabiotic-impregnated beads in orthopaedic infectious problems. KY Med Assoc 1984; 82 Jan: 25–9

    CAS  Google Scholar 

  25. Marr M, Alozozzihe G. Use of tobramycin bone cement. Drug Intell Clin Pharm 1984; 18: 883–4

    Google Scholar 

  26. Voorhoeve A, Sohr C. Ergebnisse bei der Behandlung der chronisch-eitrigen Osteomyelitis mit einem Palacos-Gentamycin-Gemisch. Munch Med Wochenschr 1973; 115: 924–30

    PubMed  CAS  Google Scholar 

  27. Scott DM, Rotschaf er JC, Behrens F. Use of vancomycin and tobramycin polymethylmethacrylate impregnated beads in the management of chronic osteomyelitis. Drug Intell Clin Pharm 1988; 22 Jun: 480–3

    Google Scholar 

  28. Soto-Hall R, Saenz L, Tavemetti R, et al. Tobramycin in bone cement: an in depth analysis of wound, serum, and urine concentrations in patients undergoing total hip revision arthroplasty. Clin Orthop 1983; 175: 60–4

    PubMed  Google Scholar 

  29. Wahlig H, Dingeldein E. Antibiotics and bone cements: experimental and clinical long-term observations. Acta Orthop Scand 1980; 51: 49–56

    Article  PubMed  CAS  Google Scholar 

  30. Hoff SF, Fitzgerald RH, Kelly PJ. The depot administration of penicillin G and gentamicin in acrylic bone cement. J Bone Joint Surg Am 1981; 63A: 798–804

    Google Scholar 

  31. Dingeldein E, Bergmann R, Wahlig H, et al. Pharmacokinetics and tolerance of gentamicin poly methyl methacrylate beads in beagle dogs. Biomaterials 1980: 315–20

  32. Pollock AV. Topical antibiotics. In Polk Jr HC, editor. Infection and the surgical patient. Edinburgh: Churchill Livingstone, 1982

    Google Scholar 

  33. Dingeldein E, Wahlig H. Freisetzung von Gentamycin aus Kunststoffkugeln während der Behandlung chronischer Knocheninfektionen [abstract no. 8]. VII. Kongress über dringliche Medizinische Hilfe, Prague; 1976: 17

  34. Wahlig H, Dingeldein E, Bergmann R, et al. The release of gentamicin from polymethylmethacrylate beads. J Bone Joint Surg Br 1978; 60B: 270–5

    Google Scholar 

  35. Torholm C, Lidgren L. Lindberg L, et al. Total hip joint arthroplasty with gentamicin impregnated cement. Clin Orthop 1983; 181: 99–106

    PubMed  Google Scholar 

  36. Petty W. Influence of methylmethacrylate on quantitative gel diffusion assay of immunoglobins. J Biomed Mater Res 1979; 13: 645–56

    Article  PubMed  CAS  Google Scholar 

  37. Panush RS, Petty W. Inhibition of human lymphocyte responses by methylmethacrylate. Clin Orthop 1978; 134: 356

    PubMed  CAS  Google Scholar 

  38. Petty W. The effect of methylmethacrylate on chemotaxis of polymorphonuclear leukocytes. J Bone Joint Surg Am 1978; 60A: 492–8

    CAS  Google Scholar 

  39. Petty W. The effect of methylmethacrylate on bacterial phagocytosis and killing by human polymorphonuclear leukocytes. J Bone Joint Surg Am 1978; 60A: 752–7

    Google Scholar 

  40. Petty W. The effect of methylmethacrylate on the bacterial inhibiting properties of normal human serum. Clin Orthop 1978; 132: 266–78

    PubMed  CAS  Google Scholar 

  41. Petty W, Caldwell JR. The effect of methylmethacrylate on complement activity. Clin Orthop 1977; 128: 354–60

    PubMed  CAS  Google Scholar 

  42. Boyden S. The chemotactic effect of mixtures of antibody and antigen on polymorphonuclear leukocytes. J Exp Med 1962; 115: 453–66

    Article  PubMed  CAS  Google Scholar 

  43. Hurley JV. Substances promoting leucocyte emigration. Ann NY Acad Sci 1964; 116: 918–35

    Article  PubMed  CAS  Google Scholar 

  44. Hurley JV, Spector WG. Endogenous factors responsible for leucocyte emigration in vivo. J Pathol Bacteriol 1961; 82: 403–20

    Article  PubMed  CAS  Google Scholar 

  45. Keller HU, Sorkin E. Studies on chemotaxis: I. On the chemotic and complement-fixing activity of globulins. Immunology 1965; 9: 241–7

    PubMed  CAS  Google Scholar 

  46. Keller HU, Sorkin E. Studies on chemotaxis: IV. The influence of serum factors of granulocyte locomotion. Immunology 1966; 10: 409–16

    Google Scholar 

  47. Keller HU, Sorkin E. Studies on chemotaxis: V. On the chemotactic effect of bacteria. Int Arch Allergy Immunol 1967; 31: 505–17

    Article  Google Scholar 

  48. Leber TH. Über die Entstehung der Entzundung und die Wirkung der entzundungserregeden Schädlichkeiten. Fortschr Med 1988; 6: 460–4

    Google Scholar 

  49. Wilkinson PC, Borel JF, Stecher-Levin VJ, et al. Macrophage and neutrophil specific chemotactic factors in serum. Nature 1969; 222: 244–7

    Article  PubMed  CAS  Google Scholar 

  50. Convery FR, Gunn DR, Hughes JD, et al. The relative safety of polymethylmethacrylate. J Bone Joint Surg Am 1975; 57A: 57–64

    Google Scholar 

  51. McLaughlin RE, DiFazio CA, Hakala M, et al. Blood clearance and acute pulmonary toxicity of methylmethacrylate in dogs after simulated arthroplasty and intravenous injection. J Bone Joint Surg Am 1973; 55A: 1621–8

    Google Scholar 

  52. Modig J, Busch C, Olerud S. The importance of intravascular coagulation, fat embolism, and acrylic monomer for respiratory and circulatory dysfunctions during intramedullary endoprosthetic surgery. Proceedings of the Orthopaedic Research Society. J Bone Joint Surg Am 1975; 57A: 583

    Google Scholar 

  53. Feith R. Side effects of acrylic cement implanted into bone. Nijmegen: Drukkerij Brakkenstein, 1975

    Google Scholar 

  54. Linder L. Tissue reaction to methylmethacrylate monomer. Acta Orthop Scand 1976; 47: 3–10

    Article  PubMed  CAS  Google Scholar 

  55. Linder L, Romanus M. Acute local tissue effects of polymerizing acrylic bone cement. Clin Orthop 1976; 58A: 358

    Google Scholar 

  56. Slooff TJJH. The influence of acrylic cement. Acta Orthop Scand 1971; 42: 465–81

    Article  PubMed  CAS  Google Scholar 

  57. Henry SL, Popham GJ, Mangino P, et al. Antibiotic impregnated beads: a production technique. Contemp Orthop 1989; 19(3): 221–6

    Google Scholar 

  58. Sande MA, Mandell GC. The aminoglycoside (antimicrobial agents). In: Gilman AG, Goodman LS, Gilman A, editors. The pharmacologic basis of therapeutics. New York: Macmillan, 1980: 1174–5

    Google Scholar 

  59. Flick AB, Herbert JC, Goodell J, et al. Noncommercial fabrication of antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop 1987; 223: 282–6

    PubMed  Google Scholar 

  60. Kirkpatrick DK, Trachtenberg LS, Mangino PD, et al. In vitro characteristics of tobramycin PMMA beads: compressive strength and leaching. Orthopaedics 1985; 8(9): 1130–3

    CAS  Google Scholar 

  61. Henry SL, Seligson D, Mangino P, et al. Antibiotic impregnated beads. Part I: bead implantation versus systemic therapy. Orthop Rev 1991; 20(3): 242–7

    PubMed  CAS  Google Scholar 

  62. Rosin H, Rosin AM, Kramer J. Determination of antibiotic levels in human bone: I. Gentamicin levels in bone. Infection 1974; 2: 3

    Article  PubMed  CAS  Google Scholar 

  63. Rodeheaver GT, Rukstalis D, Bono M, et al. A new model of bone infection used to evaluate the efficacy of antibiotic-impregnated polymethylmethacrylate cement. Clin Orthop 1983; 178: 303–11

    PubMed  CAS  Google Scholar 

  64. Buchholz HW, Elson RA, Englebrecht E, et al. Management of deep infection of total hip replacement. J Bone Joint Surg Br 1981; 63B: 342–3

    Google Scholar 

  65. Wahlig H, Dingeldein E, Buchholz HW, et al. Pharmacokinetic study of gentamicin-loaded cement in total hip replacements: comparative effects of varying dosage. J Bone Joint Surg Br 1984; 66B: 175–9

    Google Scholar 

  66. Marks KE, Nelson CL, Lautenschlager EP. Antibiotic impregnated acrylic bone cement. J Bone Joint Surg Am 1976; 58A: 358–64

    CAS  Google Scholar 

  67. Bayston R, Milner RDG. The sustained release of antimicrobial drugs from bone cement. J Bone Joint Surg Br 1982; 64B: 460–4

    Google Scholar 

  68. Elson RA, Jephcott AE, McGechie DB, et al. Bacterial infection and acrylic cement in the rat. J Bone Joint Surg Br 1977; 59B: 452–7

    Google Scholar 

  69. Chapman MW, Hadley WK. The effect of polymethylmethacrylate and antibiotic combinations on bacterial viability. J Bone Joint Surg Am 1976; 58A: 76–81

    CAS  Google Scholar 

  70. Levin PD. The effectiveness of various antibiotics in methylmethacrylate. J Bone Joint Surg Br 1975; 57B: 234–7

    Google Scholar 

  71. Calhoun JH, Mader JT. Antibiotic beads in the management of surgical infections. Am J Surg 1989; 457: 443–9

    Article  Google Scholar 

  72. Kahlmeter G. Gentamicin and tobramycin, clinical pharmacokinetics and nephrotoxicity: aspects on assay techniques. Scand J Infect Dis 1979; 18 Suppl.: 12–22

    Google Scholar 

  73. Bayston R, Milner RDG. The sustained release characteristics of antimicrobial drugs from bone cement. J Bone Joint Surg Br 1982; 64B: 460–4

    Google Scholar 

  74. Elson RA, Jephcott AE, McGechie DB, et al. Bacterial infection and acrylic cement in the rat. J Bone Joint Surg Br 1977; 59B: 452–7

    Google Scholar 

  75. Law HT, Fleming RH, McCarthy ID, et al. The mechanism of diffusion of antibiotic through acrylic bone cements. J Bone Joint Surg Br 1987; 69B: 497

    Google Scholar 

  76. VecSei V, Barquet A. Treatment of chronic osteomyelitis by necrotomy and gentamicin PMMA beads. Clin Orthop 1981; 159: 201–7

    PubMed  Google Scholar 

  77. Cierny III G, Mader IT, Penninck JJ. A clinical staging system for adult osteomyelitis. Contemp Orthop 1985; 10(5): 17–37

    Google Scholar 

  78. Law HT, Fleming RH, Gilmore MP, et al. In vitro measurement and computer modeling of the diffusion of antibiotic in bone cement. J Biomed Eng 1986; 8(2): 149–55

    Article  PubMed  CAS  Google Scholar 

  79. Bunetel L, Segui A, Cormier M, et al. Comparative study of gentamicin release from normal and low viscosity acrylic bone cement. Clin Pharmacokinet 1990; 19: 333–40

    Article  PubMed  CAS  Google Scholar 

  80. Preston DA, Wick WE. Preclinical assessment of the antibacterial activity of nebramycin factor G. Antimicrob Agents Chemother 1970; annual: 322–7

  81. Ristuccia AM, Cuhna BA. The aminoglycosides. Med Clin North Am 1982; 66(1): 303–12

    PubMed  CAS  Google Scholar 

  82. Watanakunakorn C. Penicillin combined with gentamicin and streptomycin: synergism against enterococci. Infect Dis 1971; 124: 581–6

    Article  CAS  Google Scholar 

  83. Weinstein AJ, Moellering RC. Penicillin and gentamicin therapy for enterococcal infections. JAMA 1973; 223: 1030–2

    Article  PubMed  CAS  Google Scholar 

  84. Picknell B, Mizen L, Sutherland R, et al. Antibacterial activity of antibiotics in acrylic bone cement. J Bone Joint Surg Br 1977; 59 Suppl.: 302–7

    PubMed  CAS  Google Scholar 

  85. Lawson KJ, Marks KE, Brems J, et al. Vancomycin vs tobramycin elution from polymethylmethacrylate: an in vitro study. Orthopaedics 1990; 13(5): 521–4

    CAS  Google Scholar 

  86. Born-again vancomycin [editorial]. Lancet 1985; 1: 677–8

  87. Van Rens TJG, Kayser FH, editors. Local antibiotic treatment in osteomyelitis and soft tissue infections. Amsterdam: Excerpta Medica, 1981

    Google Scholar 

  88. Eckman Jr JB, Henry SL, Mangino PD, et al. Wound and serum levels of tobramycin with the prophylactic use of tobramycin-impregnated polymethylmethacrylate beads in compound fractures. Clin Orthop 1988; 237: 213–5

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Orthopaedic Surgery, University of Louisville, School of Medicine, 3rd Floor Bridge, 530 South Jackson Street, Louisville, Kentucky, 40292, USA

    Stephen L. Henry & Kyle P. Galloway

Authors
  1. Stephen L. Henry
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kyle P. Galloway
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Henry, S.L., Galloway, K.P. Local Antibacterial Therapy for the Management of Orthopaedic Infections. Clin-Pharmacokinet 29, 36–45 (1995). https://doi.org/10.2165/00003088-199529010-00005

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003088-199529010-00005

Keywords

Search

Navigation