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Consultant Orthopaedic Surgeon
In 1958 Sir John Charnley devised the revolutionary method of joint replacement, which has been a key treatment ever since and mainly relies on the use of polymethyl methacrylate (PMMA) bone cement.(1) In 1970 Buchholz and Engelbrecht demonstrated that pulverised antibiotic mixed with the bone cement had the potential to dissolve and thus provide prophylaxis after solidification of the cement.(2) Since then, results from a great number of patients have suggested that combined local and systemic antibiotic prophylaxis is the most effective method of infection control.(3) The antibiotics added should be water-soluble, heat-resistant and powder formulation-available, but should not adversely affect the cement’s mechanical properties. More than 40 antibiotics currently satisfy these criteria and can be used for this purpose, including the aminoglucosides gentamicin, oxacillin, tobramycin, vancomycin, clindamycin and erythromycin, as well as the cephalosporins cefasoline, cefuroxime and cefamandol.(4) Nevertheless, it is mandatory to know whether the concentration of antibiotic is above the minimal inhibitory concentration (MIC), and is therefore effective, or below it, which could lead to antibiotic resistance, or even serve as a substrate for bacteria and play a role in biofilm formation.(6,7) The MIC value of gentamicin sulphate is 1 µg/ml, against the sensitive staphylococci strains.(8) Although the exact details of the elution of antibiotics are not fully understood, polymethyl metacrylate bone cement is currently used in more than one million joint replacements a year worldwide.
Several reports discuss the pharmacodynamic properties of cephalosporins and other antibiotics added to bone cement.(9–15) Aminoglycosides are the most frequently used antibiotics in orthopaedic surgery but because of their toxicity it is essential to be aware of their circulating concentration.(16–18)
In primary prosthesis implantation, the antibiotics most frequently used for adding into bone cement as a local prophylaxis are tobramycin in the USA and gentamicin sulphate in Europe (typically at 1 g gentamicin sulphate to 40 g bone cement).(3,18–26)
In the past three decades, several publications have discussed the emission of antibiotics from bone cement. They focused on the characteristics of tobramycin, the bone-penetrating capacity of ciprofloxacin, cefuroxime, cephaloridin, other cephalosporins, neomycin-bacitracin combination and cephalothin.(9,10,12,15,19–21,25,27–29)
Electron microscopy pictures reveal that after fixation, bone cement has a porous surface.(30) There is no consensus in the literature regarding antibiotic discharge from the cement. Emission can take place from the surface of the cement or through the pores and clefts within the matrix of the cement. Experiments suggest that gentamicin, after being mixed with the cement, is generally emitted from microfractures and cavities in the cement via simple diffusion.(5) Each of the different modes of antibiotic emission is dominant at different times.(14) Picknell et al observed that, regardless of which antibiotic was examined, emission correlated mainly with the extent of surface area of the cement.18 Reproducing the periprosthetic space in vitro, Hendriks et al found that the antibiotic concentration remained as high as 1,000 times above MIC,(31) and so would have a prophylactic effect against the sensitive Staphylococcus aureus strains.
Kendall et al found that in two-step hip revision surgery performed due to pyogenic infection, the antibiotic spacer had no bacteria attached to its surface.6 However, numerous publications discuss the dangers of drug resistance.(7,28,32–37)
The conclusion could be drawn from that of a study by Heck et al, who randomly questioned 2,139 orthopaedic surgeons in the USA on the use of antibiotic-loaded bone cement for prophylactic purposes: despite the lack of FDA approval, the vast majority responded that the use of antibiotic-loaded bone cement for infection prophylaxis was a routine feature of their practice.(38,39)
1. Charnley, J. Anchorage of the femoral head
prosthesis of the shaft of the femur.
J Bone Joint Surg Br 1960;42:28-30.
2. Buchholz HW, Engelbrecht H. Über die Depotwirkung einiger Antibiotica bei Vermischung mit dem Kunstharz Palacos. Chirurg 1970;41:511-5.
3. Espehaug B, Engesæter LB, Vollset SE, et al. Antibiotic prophylaxis in total hip arthroplasty. J Bone Joint Surg Br 1997;79(4):590-5.
4. Elson RA, Jephcott AE, McGechie DB, Verettas D. Antibiotic-loaded acrylic cement. J Bone Joint Surg Br 1977;59:200-5.
5. Díez-Peña E, Frutos G, Frutos P, Barrales-Rienda JM. Gentamicin sulphate release from a modified commercial acrylic surgical radiopaque bone cement. Chem Pharm Bull 2002;50(9):1201-8.
6. Kendall RW, Duncan CP, Beauchamp CP. Bacterial growth on antibiotic-loaded acrylic cement. J Arthroplasty 1995;10(6):817-22.
7. Van de Belt H, Neut D, Schenk W, et al. Gentamicin release from polymethylmethacrylate bone cements and Staphylococcus aureus biofilm formation. Acta Orthop Scand 2000;71(6):625-9.
8. British Society for Antimicrobial Chemotherapy.
A guide to sensitivity testing. J Antimicrob Chemother 1991;27:Suppl D:1-50.
9. Endler M, Wewalka G. Antibiotic concentration in postoperative wound secretions and in serum of patients after implantation of hip endoprostheses having used neomycin-bacitracin loaded bone cement. Wien Klin Wochenschr 1980;92(12):443-7.
10. Innes A, Hughes SP, Robertson S, Dash CH. Cefuroxime in CMW bone cement. Int Orthop 1985;9(4):265-9.
11. Marks KE, Nelson CL, Lautenschlager EP. Antibiotic-impregnated acrylic bone cement. J Bone Joint Surg Am 1976;58(3):358-64.
12. Overbeck JP, Winckler ST, Meffert R, et al. Penetration of ciprofloxacin into bone. J Invest Surg 1995;8(3):155-62.
13. Picknell B, Mizen L, Sutherland R. Antibacterial activity of antibiotics in acrylic bone cement.
J Bone Joint Surg Br 1977;59-B(3):302-7.
14. Van de Belt H, Neut D, Schenk W, et al. Infection of orthopedic implants and the use of antibiotic-loaded bone cements. Acta Orthop Scand 2001;72(6):557-71.
15. Welch AB. Antibiotics in acrylic bone cement.
J Biomed Mater Res 1978;12(6):843-55.
16. Haydon RC, Blaha JD, Mancinelli C, Koike K. Audiometric thresholds in osteomyelitis patients treated with gentamicin-impregnated methylmethacrylate beads (Septopal). Clin Orthop 1993;295:43-6.
17. Lodenkamper H, Lodenkamper U, Trompa K. Über die Ausscheidung von Antibiotika aus dem Knochenzement Palacos Z Orthop 1982;120:801-5.
18. Powles JW, Spencer RF, Lovering AM. Gentamicin release from old cement during revision hip arthroplasty. J Bone Joint Surg Br 1998;80(4):607-10.
19. Nijhoff MW, Dhert WJ, Fleer A, et al. Prophylaxis of implant-related staphylococcal infections using tobramycin-containing bone cement.
J Biomed Mater Res 2000;15;52(4):754-61.
20. Pritchett JW, Bortel DT. Tobramycin-impregnated cement in total hip replacements. Orthop Rev 1992;21(5):577-9.
21. Soto-Hall R, Saenz L, Tavernetti R, et al. Tobramycin in bone cement. Clin Orthop 1983;(175):60-4.
22. Downes S, Brown AE, Mukherjee S. The clearance of gentamicin from antibiotic-loaded bone cement. Int Orthop 1985;9(3):205-7.
23. Langlais F, Bunetel L, Segui A, et al. Antibiotic-loaded orthopedic cements. Rev Chir Orthop Reparatrice Appar Mot 1988;74(6):493-503.
24. Torrado S, Frutos P, Frutos G. Gentamicin bone cements. Int J Pharm 2001;217(1-2):57-69.
25. Wahlig H, Dingeldein E, Buchholz HW, et al. Pharmacokinetic study of gentamicin-loaded cement in total hip replacements. J Bone Joint Surg Br 1984;66(2):175-9.
26. Wahlig H, Dingeldein E. Antibiotics and bone cements. Acta Orthop Scand 1980;51(1):49-56.
27. Brien WW, Salvati EA, Klein R, et al. Antibiotic impregnated bone cement in total hip arthroplasty.
Clin Orthop 1993;(296):242-8.
28. Hope PG, Kristinsson KG, Norman P, Elson RA. Deep infection of cemented total hip arthroplasties caused by coagulase-negative staphylococci. J Bone Joint Surg Br 1989;71(5):851-5.
29. Nungu KS, Larsson S, Wallinder L, Holm S. Bone and fluid concentrations of cefalosporins. Acta Orthop Scand 1995;66(2):161-5.
30. Baker AS, Geenham LW. Release of gentamicin from acrylic bone cement. J Bone Joint Surg (Am)
31. Hendriks JG, Neut D, Van Horn JR, et al. The release of gentamicin from acrylic bone cements in a simulated prosthesis-related interfacial gap. J Biomed Mater Res 2003;15;64B(1):1-5.
32. Ceffa R, Andreoni S, Borre S, et al. Mucoraceae infections of antibiotic-loaded cement spacers in the treatment of bacterial infections caused by knee arthroplasty. J Arthroplasty 2002;17(2):235-8.
33. Kendall RW, Duncan CP, Smith JA, Ngui-Yen JH. Persistence of bacteria on antibiotic loaded acrylic depots. Clin Orthop 1996;(329):273-80.
34. Oga M, Arizono T, Sugioka Y, et al. The inhibition of bacterial adhesion to a tobramycin-impregnated polymethylmethacrylate substratum.
J Long Term Eff Med Implants 1992;1(4):321-8.
35. Thomes B, Murray P, Bouchier-Hayes D.
Development of resistant strains of Staphylococcus epidermidis on gentamicin-loaded bone cement in vivo. J Bone Joint Surg Br 2002;84(5):758-60.
36. Van de Belt H, Neut D, Schenk W, et al. Staphylococcus aureus biofilm formation on different gentamicin-loaded polymethylmethacrylate bone cements. Biomaterials 2001;22(12):1607-11.
37. Walenkamp GH. Gentamicin PMMA beads and other local antibiotic carriers in two-stage revision of total knee infection. J Chemother 2001;13Spec1(1):66-72.
38. Heck D, Rosenberg A, Schink-Ascani M, et al. Use of antibiotic-impregnated cement during hip and knee arthroplasty in the United States. J Arthroplasty 1995;10:470-5.
39. Lawson KJ, Marks KE, Brems J, Rehm S. Vancomycin vs tobramycin elution from polymethylmethacrylate. Orthopedics 1990;13:521-4.