Biodegradable vs non-biodegradable antibiotic delivery devices in the treatment of osteomyelitis

Expert Opinion on Drug Delivery

Volumn 10, Issue 3, 2013, Pages 341-351

  Kluin, Otto S ^a   Van Der Mei, Henny C ^a   Busscher, Henk J ^a   Neut, Daniëlle ^a  

^a UNIVERSITY MEDICAL CENTER GRONINGEN   (Netherlands)

Author keywords

Antibiotics; Carrier; Degradable; Osteomyelitis; PMMA; Release; Treatment

Indexed keywords

AMINOGLYCOSIDE ANTIBIOTIC AGENT; ANTIBIOTIC AGENT; CALCIUM PHOSPHATE; CALCIUM SULFATE; COLLAGEN SPONGE; GENTAMICIN BONE CEMENT; POLY(METHYL METHACRYLATE); POLYLACTIC ACID;

ANTIBIOTIC THERAPY; BACTERIAL COLONIZATION; BIODEGRADABLE DELIVERY DEVICE; BONE TRANSPLANTATION; CHRONIC OSTEOMYELITIS; DRUG DELIVERY DEVICE; DRUG INCOMPATIBILITY; DRUG RELEASE; HUMAN; NON BIODEGRADABLE DELIVERY DEVICE; OSTEOMYELITIS; REVIEW;

ABSORBABLE IMPLANTS; ANIMALS; ANTI-BACTERIAL AGENTS; DIOXANES; DRUG DELIVERY SYSTEMS; HUMANS; LACTIC ACID; OSTEOMYELITIS; POLYMERS; POLYMETHYL METHACRYLATE;

EID: 84873889769     PISSN: 17425247     EISSN: 17447593     Source Type: Journal    
DOI: 10.1517/17425247.2013.751371     Document Type: Review

References (115)

1. McGrory JE, Pritchard DJ, Unni KK, et al. Malignant lesions arising in chronic osteomyelitis. Clin Orthop Relat Res 1999;362:181-9 (Pubitemid 29226780)
2. Eisenberg JM, Kitz DS. Savings from outpatient antibiotic therapy for osteomyelitis. Economic analysis of a therapeutic strategy. JAMA 1986;255:1584-8 (Pubitemid 16167479)
3. Lautenschlager S, Herzog C, Zimmerli W. Course and outcome of bacteremia due to Staphylococcus aureus: evaluation of different clinical case definitions. Clin Infect Dis 1993;16:567-73 (Pubitemid 23121074)
4. Engesaeter LB, Espehaug B, Lie SA, et al. Does cement increase the risk of infection in primary total hip arthroplasty? Revision rates in 56,275 cemented and uncemented primary THAs followed for 0-16 years in the Norwegian Arthroplasty Register. Acta Orthop 2006;77:351-8 (Pubitemid 43977388)
5. Boulton AJ, Vileikyte L, Ragnarson-Tennvall G, Apelqvist J. The global burden of diabetic foot disease. Lancet 2005;366:1719-24 (Pubitemid 41587452)
6. Baumert N, von Eiff C, Schaaff F, et al. Physiology and antibiotic susceptibility of Staphylococcus aureus small colony variants. Microb Drug Resist 2002;8:253-60 (Pubitemid 36043690)
7. Stewart PS. Mechanisms of antibiotic resistance in bacterial biofilms. Int J Med Microbiol 2002;292:107-13 (Pubitemid 34842181)
8. Costerton JW, Lewandowski Z, Caldwell DE, et al. Microbial biofilms. Annu Rev Microbiol 1995;49:711-45
9. Gentry LO, Rodriguez-Gomez G. Ofloxacin versus parenteral therapy for chronic osteomyelitis. Antimicrob Agents Chemother 1991;35:538-41
10. Mader JT, Cantrell JS, Calhoun J. Oral ciprofloxacin compared with standard parenteral antibiotic therapy for chronic osteomyelitis in adults. J Bone Joint Surg Am 1990;72:104-10 (Pubitemid 20076564)
11. Rissing JP. Antimicrobial therapy for chronic osteomyelitis in adults: role of the quinolones. Clin Infect Dis 1997;25:1327-33 (Pubitemid 28022665)
12. Waldvogel FA, Medoff G, Swartz MN. Treatment of osteomyelitis. N Engl J Med 1970;283:822
13. Waldvogel FA, Papageorgiou PS. Osteomyelitis: the past decade. N Engl J Med 1980;303:360-70 (Pubitemid 10035062)
14. Guglielmo BJ, Luber AD, Paletta D Jr, Jacobs RA. Ceftriaxone therapy for staphylococcal osteomyelitis: a review. Clin Infect Dis 2000;30:205-7 (Pubitemid 30067086)
15. Conterno LO, da Silva Filho CR. Antibiotics for treating chronic osteomyelitis in adults. Cochrane Database Syst Rev 2009;3:CD004439
16. Hermsen ED, Hanson M, Sankaranarayanan J, et al. Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections. Expert Opin Drug Saf 2010;9:9-14
17. Diefenbeck M, Muckley T, Hofmann GO. Prophylaxis and treatment of implant-related infections by local application of antibiotics. Injury 2006;37:S95-104
18. Neut D, Van de Belt H, Van Horn JR, et al. Residual gentamicin-release from antibiotic-loaded polymethylmethacrylate beads after 5 years of implantation. Biomaterials 2003;24:1829-31 (Pubitemid 36184738)
19. Charnley J. Clinical experiences with self-curing acrylic cement. In: Acrylic cement in orthopaedic surgery. Edinburgh, E&S Livingstone; 1970. p. 33-5
20. Buchholz HW, Gartmann HD. Infection prevention and surgical management of deep insidious infection in total endoprosthesis. ("Infektionsprophylaxe und operative Behandlung der schleichende tiefen Infektionen bei totalen Endoprothesen"). Chirurg 1972;43:446-53
21. Josefsson G, Kolmert L. Prophylaxis with systematic antibiotics versus gentamicin bone cement in total hip arthroplasty. A ten-year survey of 1,688 hips. Clin Orthop Relat Res 1993;292:210-14 (Pubitemid 23206271)
22. Dunbar MJ. Antibiotic bone cements: their use in routine primary total joint arthroplasty is justified. Orthopedics 2009;32:9
23. Buchholz HW, Elson RA, Engelbrecht E, et al. Management of deep infection of total hip replacement. J Bone Joint Surg Br 1981;63:342-53 (Pubitemid 11039510)
24. Wroblewski BM. One-stage revision of infected cemented total hip arthroplasty. Clin Orthop Relat Res 1986;211:103-7 (Pubitemid 17181335)
25. Hsieh PH, Shih CH, Chang YH, et al. Two-stage revision hip arthroplasty for infection: comparison between the interim use of antibiotic-loaded cement beads and a spacer prosthesis. J Bone Joint Surg Am 2004;86:1989-97
26. Barth RE, Vogely HC, Hoepelman AI, Peters EJ. 'To bead or not to bead?' Treatment of osteomyelitis and prosthetic joint-associated infections with gentamicin bead chains. Int J Antimicrob Agents 2011;38:371-5
27. Evans RP, Nelson CL. Gentamicin-impregnated polymethylmethacrylate beads compared with systemic antibiotic therapy in the treatment of chronic osteomyelitis. Clin Orthop Relat Res 1993;295:37-42 (Pubitemid 23299628)
28. 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 (Pubitemid 41102406)
29. Walenkamp GH, Vree TB, Van Rens TJ. Gentamicin-PMMA beads. Pharmacokinetic and nephrotoxicological study. Clin Orthop Relat Res 1986;205:171-83 (Pubitemid 16011268)
30. Baker AS, Greenham LW. Release of gentamicin from acrylic bone cement. Elution and diffusion studies. J Bone Joint Surg Am 1988;70:1551-7 (Pubitemid 19038650)
31. Khoury AE, Lam K, Ellis B, Costerton JW. Prevention and control of bacterial infections associated with medical devices. ASAIO J 1992;38:174-8
32. Schurman DJ, Trindade C, Hirshman HP, et al. Antibiotic-acrylic bone cement composites. Studies of gentamicin and Palacos. J Bone Joint Surg Am 1978;60:978-84
33. Picknell B, Mizen L, Sutherland R. Antibacterial activity of antibiotics in acrylic bone cement. J Bone Joint Surg Br 1977;59:302-7 (Pubitemid 8168943)
34. Hoff SF, Fitzgerald RH Jr, Kelly PJ. The depot administration of penicillin G and gentamicin in acrylic bone cement. J Bone Joint Surg Am 1981;63:798-804 (Pubitemid 11127665)
35. Torholm C, Lidgren L, Lindberg L, Kahlmeter G. Total hip joint arthroplasty with gentamicin-impregnated cement. A clinical study of gentamicin excretion kinetics. Clin Orthop Relat Res 1983;181:99-106 (Pubitemid 14215205)
36. Chohfi M, Langlais F, Fourastier J, et al. Pharmacokinetics, uses, and limitations of vancomycin-loaded bone cement. Int Orthop 1998;22:171-7 (Pubitemid 28388731)
37. Van de Belt H, Neut D, Uges DR, et al. Surface roughness, porosity and wettability of gentamicin-loaded bone cements and their antibiotic release. Biomaterials 2000;21:1981-7 (Pubitemid 30433826)
38. Neut D, Van de Belt H, Van Horn JR, et al. The effect of mixing on gentamicin release from polymethylmethacrylate bone cements. Acta Orthop Scand 2003;74:670-6 (Pubitemid 38067867)
39. Hessert GR, Ruckdeschel G. Antibiotic effects of mixtures of polymethylmethacrylate with antibiotics ("Antibiotische Wirksamkeit von Mischungen des Polymethylmethacrylates mit Antibiotica"). Arch Orthop Unfallchir 1970;68:249-54
40. Anguita-Alonso P, Rouse MS, Piper KE, et al. Comparative study of antimicrobial release kinetics from polymethylmethacrylate. Clin Orthop Relat Res 2006;445:239-44 (Pubitemid 44341351)
41. Seldes RM, Winiarsky R, Jordan LC, et al. Liquid gentamicin in bone cement: a laboratory study of a potentially more cost-effective cement spacer. J Bone Joint Surg Am 2005;87:268-72 (Pubitemid 40216622)
42. Lautenschlager EP, Marshall GW, Marks KE, et al. Mechanical strength of acrylic bone cements impregnated with antibiotics. J Biomed Mater Res 1976;10:837-45
43. Wahlig H. Kinetics of the liberation of antibiotics from bone cements-results of comparative studies in vitro and in vivo. "U? ber die Freisetzungskinetik von Antibiotika aus Knochenzementen - Ergebnisse vergleichender Untersuchungen in vitro und in vivo". Aktuelle Probl Chir Orthop 1987;31:221-6
44. Atkinson BA, Lorian V. Antimicrobial agent susceptibility patterns of bacteria in hospitals from 1971 to 1982. J Clin Microbiol 1984;20:791-6 (Pubitemid 14006083)
45. Adams K, Couch L, Cierny G, et al. In vitro and in vivo evaluation of antibiotic diffusion from antibiotic-impregnated polymethylmethacrylate beads. Clin Orthop 1992;278:244-52
46. Klemm K. The use of antibiotic-containing bead chains in the treatment of chronic bone infections. Clin Microbiol Infect 2001;7:28-31 (Pubitemid 34960262)
47. Mader JT, Calhoun J, Cobos J. In vitro evaluation of antibiotic diffusion from antibiotic-impregnated biodegradable beads and polymethylmethacrylate beads. Antimicrob Agents Chemother 1997;41:415-18 (Pubitemid 27111039)
48. Klekamp J, Dawson JM, Haas DW, et al. The use of vancomycin and tobramycin in acrylic bone cement: biomechanical effects and elution kinetics for use in joint arthroplasty. J Arthroplasty 1999;14:339-46 (Pubitemid 29172251)
49. Chang Y, Chen WC, Hsieh PH, et al. In vitro activities of daptomycin-, vancomycin-, and teicoplanin-loaded polymethylmethacrylate against methicillin-susceptible, methicillin-resistant, and vancomycin-intermediate strains of Staphylococcus aureus. Antimicrob Agents Chemother 2011;55:5480-4
50. Ensing GT, Neut D, Van Horn JR, et al. The combination of ultrasound with antibiotics released from bone cement decreases the viability of planktonic and biofilm bacteria: an in vitro study with clinical strains. J Antimicrob Chemother 2006;58:1287-90 (Pubitemid 44884155)
51. Neut D, Hendriks JG, Van Horn JR, et al. Antimicrobial efficacy of gentamicin-loaded acrylic bone cements with fusidic acid or clindamycin added. J Orthop Res 2006;24:291-9 (Pubitemid 43773040)
52. Giavaresi G, Bertazzoni Minelli E, Sartori M, et al. Microbiological and pharmacological tests on new antibiotic-loaded PMMA-based composites for the treatment of osteomyelitis. J Orthop Res 2012;30:348-55
53. Moojen DJ, Hentenaar B, Charles Vogely H, et al. In vitro release of antibiotics from commercial PMMA beads and articulating hip spacers. J Arthroplasty 2008;23:1152-6
54. Nelson CL, Griffin FM, Harrison BH, et al. In vitro elution characteristics of commercially and noncommercially prepared antibiotic PMMA beads. Clin Orthop 1992;284:303-9
55. Van de Belt H, Neut D, Van Horn JR, et al. ... or not to treat? Nat Med 1999;5:358-9
56. Bloomfield MR, Klika AK, Barsoum WK. Antibiotic-coated spacers for total hip arthroplasty infection. Orthopedics 2010;33:649
57. Henry SL, Galloway KP. Local antibacterial therapy for the management of orthopaedic infections. Pharmacokinetic considerations. Clin Pharmacokinet 1995;29:36-45
58. Greene N, Holtom PD, Warren CA, et al. In vitro elution of tobramycin and vancomycin polymethylmethacrylate beads and spacers from Simplex and Palacos. Am J Orthop (Belle Mead NJ) 1998;27:201-5
59. Holtom PD, Warren CA, Greene NW, et al. Relation of surface area to in vitro elution characteristics of vancomycin-impregnated polymethylmethacrylate spacers. Am J Orthop (Belle Mead NJ) 1998;27:207-10
60. Cui Q, Mihalko WM, Shields JS, et al. Antibiotic-impregnated cement spacers for the treatment of infection associated with total hip or knee arthroplasty. J Bone Joint Surg Am 2007;89:871-82 (Pubitemid 46564296)
61. Van Raaij TM, Visser LE, Vulto AG, Verhaar JA. Acute renal failure after local gentamicin treatment in an infected total knee arthroplasty. J Arthroplasty 2002;17:948-50
62. Hanssen AD, Spangehl MJ. Practical applications of antibiotic-loaded bone cement for treatment of infected joint replacements. Clin Orthop Relat Res 2004;427:79-85 (Pubitemid 39362835)
63. McLaren AC. Alternative materials to acrylic bone cement for delivery of depot antibiotics in orthopaedic infections. Clin Orthop Relat Res 2004;427:101-6 (Pubitemid 39362838)
64. Siepmann J, Gopferich A. Mathematical modeling of bioerodible, polymeric drug delivery systems. Adv Drug Deliv Rev 2001;48:229-47 (Pubitemid 32434405)
65. Zilberman M, Elsner JJ. Antibiotic-eluting medical devices for various applications. J Control Release 2008;130:202-15
66. Stemberger A, Grimm H, Bader F, et al. Local treatment of bone and soft tissue infections with the collagen-gentamicin sponge. Eur J Surg Suppl 1997;578:17-26 (Pubitemid 27213784)
67. Rutten HJT, Nijuis PHA. Prevention of wound infection in elective colorectal surgery by local application of a gentamicin containing collagen sponge. Eur J Surg 1997;578:S31-5
68. Sørensen TS, Sørensen AI, Merser S. Rapid release of gentamicin from collagen sponge. Acta Orthop Scand 1990;61:353-6
69. Dinopoulos H, Dimitriou R, Giannoudis PV. Bone graft substitutes: what are the options? Surgeon 2012;10:230-9
70. Witsø E, Persen L, Benum P, et al. High local concentrations without systemic adverse effects after impaction of netilmicin-impregnated bone. Acta Orthop Scand 2004;75:339-46 (Pubitemid 38824212)
71. Winkler H. Rationale for one stage exchange of infected hip replacement using uncemented implants and antibiotic impregnated bone graft. Int J Med Sci 2009;6:247-52
72. Lewis CS, Katz J, Baker MI, et al. Local antibiotic delivery with bovine cancellous chips. J Biomater Appl 2011;26:491-506
73. Buttaro M, Comba F, Piccaluga F. Vancomycin-supplemented cancellous bone allografts in hip revision surgery. Clin Orthop Relat Res 2007;461:74-80 (Pubitemid 47344097)
74. Dreesmann H. About bone filling "Uber knochenplombbierung". Beitr Klin Chir 1982;9:804-10
75. Rauschmann MA, Wichelhaus TA, Stirnal V, et al. Nanocrystalline hydroxyapatite and calcium sulphate as biodegradable composite carrier material for local delivery of antibiotics in bone infections. Biomaterials 2005;26:2677-84 (Pubitemid 39600720)
76. Chang W, Colangeli M, Colangeli S, et al. Adult osteomyelitis: debridement versus debridement plus Osteoset T pellets. Acta Orthop Belg 2007;73:238-43
77. El-Husseiny M, Patel S, MacFarlane RJ, Haddad FS. Biodegradable antibiotic delivery systems. J Bone Joint Surg Br 2011;93:151-7
78. Ziran BH, Smith WR, Morgan SJ. Use of calcium-based demineralized bone matrix/allograft for nonunions and posttraumatic reconstruction of the appendicular skeleton: preliminary results and complications. J Trauma 2007;63:1324-8
79. Wichelhaus TA, Dingeldein E, Rauschmann M, et al. Elution characteristics of vancomycin, teicoplanin, gentamicin and clindamycin from calcium sulphate beads. J Antimicrob Chemother 2001;48:117-19 (Pubitemid 32684735)
80. Heijink A, Yaszemski MJ, Patel R, et al. Local antibiotic delivery with OsteoSet, DBX, and Collagraft. Clin Orthop Relat Res 2006;451:29-33 (Pubitemid 44511304)
81. Webb ND, McCanless JD, Courtney HS, et al. Daptomycin eluted from calcium sulfate appears effective against Staphylococcus. Clin Orthop Relat Res 2008;466:1383-7
82. McLaren AC, McLaren SG, Nelson CL, et al. The effect of sampling method on the elution of tobramycin from calcium sulfate. Clin Orthop Relat Res 2002;403:54-7 (Pubitemid 35168356)
83. Turner TM, Urban RM, Gitelis S, et al. Radiographic and histologic assessment of calcium sulfate in experimental animal models and clinical use as a resorbable bone-graft substitute, a bone-graft expander, and a method for local antibiotic delivery. One institution's experience. J Bone Joint Surg Am 2001;83:S8-18
84. Blokhuis TJ, Termaat MF, Den Boer FC, et al. Properties of calcium phosphate ceramics in relation to their in vivo behavior. J Trauma 2000;48:179-86 (Pubitemid 30054327)
85. Larsson S. Calcium phosphates: what is the evidence? J Orthop Trauma 2010;24:S41-5
86. Stallmann HP, Faber C, Bronckers AL, et al. In vitro gentamicin release from commercially available calcium-phosphate bone substitutes influence of carrier type on duration of the release profile. BMC Musculoskelet Disord 2006;7:18-25
87. Korkusuz F, Uchida A, Shinto Y, et al. Experimental implant-related osteomyelitis treated by antibiotic-calcium hydroxyapatite ceramic composites. J Bone Joint Surg Br 1993;75:111-14 (Pubitemid 23052429)
88. Shirtliff ME, Calhoun JH, Mader JT. Experimental osteomyelitis treatment with antibiotic-impregnated hydroxyapatite. Clin Orthop Relat Res 2002;401:239-47 (Pubitemid 34832855)
89. Zelken J, Wanich T, Gardner M, et al. PMMA is superior to hydroxyapatite for colony reduction in induced osteomyelitis. Clin Orthop Relat Res 2007;462:190-4 (Pubitemid 47367862)
90. Zhang X, Jia W, Gu Y, et al. Teicoplanin-loaded borate bioactive glass implants for treating chronic bone infection in a rabbit tibia osteomyelitis model. Biomaterials 2010;31:5865-74
91. Xie Z, Liu X, Jia W, et al. Treatment of osteomyelitis and repair of bone defect by degradable bioactive borate glass releasing vancomycin. J Control Release 2009;139:118-26
92. Garvin K, Feschuk C. Polylactide-polyglycolide antibiotic implants. Clin Orthop Relat Res 2005;437:105-10 (Pubitemid 41099074)
93. Garvin KL, Miyano JA, Robinson D, et al. Polylactide/polyglycolide antibiotic implants in the treatment of osteomyelitis. A canine model. J Bone Joint Surg Am 1994;76:1500-6 (Pubitemid 24355966)
94. Kanellakopoulou K, Kolia M, Anastassiadis A, et al. Lactic acid polymers as biodegradable carriers of fluoroquinolones: an in vitro study. Antimicrob Agents Chemother 1999;43:714-16 (Pubitemid 29109551)
95. Bostman O, Hirvensalo E, Makinen J, Rokkanen P. Foreign-body reactions to fracture fixation implants of biodegradable synthetic polymers. J Bone Joint Surg Br 1977;72:592-6
96. Taylor MS, Daniels AU, Andriano KP, Heller J. Six bioabsorbable polymers: in vitro acute toxicity of accumulated degradation products. J Appl Biomater 1994;5:151-7
97. Ding AG, Schwendeman SP. Acidic microclimate pH distribution in PLGA microspheres monitored by confocal laser scanning microscopy. Pharm Res 2008;25:2041-52
98. Ulery BD, Nair LS, Laurencin CT. Biomedical applications of biodegradable polymers. J Polym Sci B Polym Phys 2011;49:832-64
99. Ueda H, Tabata Y. Polyhydroxyalkanonate derivatives in current clinical applications and trials. Adv Drug Deliv Rev 2003;55:501-18 (Pubitemid 36426927)
100. Zhang Z, Kuijer R, Bulstra SK, et al. The in vivo and in vitro degradation behavior of poly(trimethylene carbonate). Biomaterials 2006;27:1741-8 (Pubitemid 41759468)
101. Pêgo AP, Van Luyn MJ, Brouwer LA, et al. In vivo behavior of poly (1,3-trimethylene carbonate) and copolymers of 1,3-trimethylene carbonate with D,L-lactide or epsilon-caprolactone: degradation and tissue response. J Biomed Mater Res A 2003;67:1044-54 (Pubitemid 37521581)
102. Bat E, Van Kooten TG, Feijen J, Grijpma DW. Macrophage-mediated erosion of gamma irradiated poly (trimethylene carbonate) films. Biomaterials 2009;30:3652-61
103. Van Leeuwen AC, Van Kooten TG, Grijpma DW, Bos RRM. In vivo behaviour of a biodegradable poly (trimethylene carbonate) barrier membrane: a histological study in rats. J Mater Sci Mater Med 2012;23:1951-9
104. Kluin OS, Van der Mei HC, Busscher HJ, Neut D. A surface-eroding antibiotic delivery system based on poly- (trimethylene carbonate). Biomaterials 2009;30:4738-42
105. Nandi SK, Mukherjee P, Roy S, et al. Local antibiotic delivery systems for the treatment of osteomyelitis - a review. Mater Sci Eng C Mater Biol Appl 2009;29:2478-85
106. Lucke M, Schmidmaier G, Sadoni S, et al. Gentamicin coating of metallic implants reduces implant-related osteomyelitis in rats. Bone 2003;32:521-31 (Pubitemid 39665711)
107. Schmidmaier G, Lucke M, Wildemann B, et al. Prophylaxis and treatment of implant-related infections by antibiotic-coated implants: a review. Injury 2006;37:S105-12
108. Neut D, Dijkstra RJ, Thompson JI, et al. A gentamicin-releasing coating for cementless hip prostheses-longitudinal evaluation of efficacy using in vitro bio-optical imaging and its wide-spectrum antibacterial efficacy. J Biomed Mater Res A 2012;100(12):3220-6
109. Rasyid HN, Van der Mei HC, Frijlink HW, et al. Concepts for increasing gentamicin release from handmade bone cement beads. Acta Orthop 2009;80:508-13
110. Kent M, Rachha R, Sood M. A technique for the fabrication of a reinforced moulded articulating cement spacer in two-stage revision total hip arthroplasty. Int Orthop 2010;34:949-53
111. Samuel S, Ismavel R, Boopalan PR, Matthai T. Practical considerations in the making and use of high-dose antibioticloaded bone cement. Acta Orthop Belg 2010;76:543-5
112. Van Thiel GS, Berend KR, Klein GR, et al. Intraoperative molds to create an articulating spacer for the infected knee arthroplasty. Clin Orthop Relat Res 2011;469:994-1001
113. Degen RM, Davey JR, Davey JR, et al. Does a prefabricated gentamicin-impregnated, load-bearing spacer control periprosthetic hip infection? Clin Orthop Relat Res 2012;470:2724-9
114. Jia WT, Luo SH, Zhang CQ, Wang JQ. In vitro and in vivo efficacies of teicoplanin-loaded calcium sulfate for treatment of chronic methicillin- resistant Staphylococcus aureus osteomyelitis. Antimicrob Agents Chemother 2010;54:170-6
115. Niikura T, Tsujimoto K, Yoshiya S, et al. Vancomycin-impregnated calcium phosphate cement for methicillin-resistant Staphylococcus aureus femoral osteomyelitis. Orthopedics 2007;30:320-1 (Pubitemid 46824489)