Isoniazid Could Be Used for Antibiotic-loaded Bone Cement for Musculoskeletal Tuberculosis: An In Vitro Study
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Antibiotic-loaded bone cement (ALBC) has been used in serious cases of musculoskeletal tuberculosis, but the type and amount of antibiotic that should be used in ALBC have not been determined.
We therefore determined the (1) elution characteristics and (2) antimycobacterial activity of isoniazid- and rifampicin-loaded bone cement.
A total of 240 elution samples of each of three discs from 40 g bone cement mixed with one of eight dosages: 1 g, 2 g, and 4 g isoniazid, 1 g, 2 g, and 4 g rifampicin, and a combination of 1 + 1 g or 2 + 2 g of isoniazid and rifampicin. The polymerization of rifampicin-loaded bone cement was delayed to mean 122.5 ± 31.1 minutes. We measured the quantity of isoniazid and rifampicin and the antimycobacterial activity on Days 1, 3, 7, 14, and 30.
Isoniazid eluted in almost all the samples while rifampicin was detected only on Day 1 with 2 g (0.7 ± 0.4 ug/mL/day), and until Day 14 with 4 g (0.1 ± 0.0u g/mL/day). Most of the samples containing isoniazid showed antimycobacterial activity while the samples containing rifampicin showed antimycobacterial activity only on Day 1 with 1 g (0.52 ± 0.18 ug/mL), until Day 14 with 2 g (0.03 ± 0.00 ug/mL), and until Day 30 with 4 g (1.84 ± 1.90 ug/mL).
The data suggest isoniazid could be considered for use in ALBC for musculoskeletal tuberculosis if used with systemic treatment. For preventing resistance and systemic toxicity, a combination with a second-line drug and an in vivo study would be needed.
- Anguita-Alonso P, Rouse MS, Piper KE, Jacofsky DJ, Osmon DR, Patel R. Comparative study of antimicrobial release kinetics from polymethylmethacrylate. Clin Orthop Relat Res. 2006;445:239–244.
- Beeching NJ, Thomas MG, Roberts S, Lang SD. Comparative in-vitro activity of antibiotics incorporated in acrylic bone cement. J Antimicrob Chemother. 1986;17:173–184. CrossRef
- Bennett WM, Singer I, Golper T, Feig P, Coggins CJ. Guidelines for drug therapy in renal failure. Ann Intern Med. 1977;86:754–783. CrossRef
- Biron F. [Resection of the knee joint][in German]. Z Orthop Ihre Grenzgeb. 1965;100:221–225.
- Bridgens J, Davies S, Tilley L, Norman P, Stockley I. Orthopaedic bone cement: do we know what we are using? J Bone Joint Surg Br. 2008;90:643–647.
- Bryan WJ, Doherty JH Jr, Sculco TP. Tuberculosis in a rheumatoid patient: a case report. Clin Orthop Relat Res. 1982;171:206–208.
- Buchholz HW, Engelbrecht H. [Depot effects of various antibiotics mixed with Palacos resins][in German]. Chirurg. 1970;41:511–515.
- Campos OP. Bone and joint tuberculosis and its treatment. J Bone Joint Surg Am. 1955;37:937–966.
- Case records of the Massachusetts General Hospital. Weekly clinicopathological exercises: Case 43-1983. An elderly man with progressive pain and swelling of the knee. N Engl J Med. 1983;309:1042–1049.
- Changsen C, Franzblau SG, Palittapongarnpim P. Improved green fluorescent protein reporter gene-based microplate screening for antituberculosis compounds by utilizing an acetamidase promoter. Antimicrob Agents Chemother. 2003;47:3682–3687. CrossRef
- Chohfi M, Langlais F, Fourastier J, Minet J, Thomazeau H, Cormier M. Pharmacokinetics, uses, and limitations of vancomycin-loaded bone cement. Int Orthop. 1998;22:171–177. CrossRef
- Collins LA, Torrero MN, Franzblau SG. Green fluorescent protein reporter microplate assay for high-throughput screening of compounds against Mycobacterium tuberculosis. Antimicrob Agents Chemother. 1998;42:344–347.
- De Palma L, Greco F, Ciarpaglini C, Caneva C. The mechanical properties of “cement-antibiotic” mixtures. Ital J Orthop Traumatol. 1982;8:461–467.
- Dhillon J, Mitchison DA. Activity and penetration of antituberculosis drugs in mouse peritoneal macrophages infected with Mycobacterium microti OV254. Antimicrob Agents Chemother. 1989;33:1255–1259. CrossRef
- Fowler GR. Is resection of the knee-joint justifiable in children? Ann Surg. 1889;9:439–445. CrossRef
- Galasso O, Mariconda M, Calonego G, Gasparini G. Physical, mechanical and pharmacological properties of coloured bone cement with and without antibiotics. J Bone Joint Surg Br. 2011;93:1529–1536.
- Gelikonova VS. [Conservative resection of the knee joint in the treatment of tuberculous gonitis in children as seen in the light of remote results][in Russian]. Ortop Travmatol Protez. 1957;18:38–44.
- Girdlestone GR. The pathology and treatment of tuberculosis of the knee-joint. Br J Surg. 1932;19:488–507. CrossRef
- Hand WL, King-Thompson NL, Steinberg TH. Interactions of antibiotics and phagocytes. J Antimicrob Chemother. 1983;12(suppl C):1–11. CrossRef
- Harris HW. Current concepts of the metabolism of antituberculous agents. Ann N Y Acad Sci. 1963;106:43–47. CrossRef
- Hibbs RA. The treatment of tuberculosis of the joints of the lower extremities by operative fusion. J Bone Joint Surg Am. 1930;12:749–754.
- Jenkin G. Isoniazid. In: Grayson ML, Kucers A, Crowe S, McCarthy J, Mills J, eds. Kucers’ The Use ofAantibiotics: A Clinical Review of Antibacterial, Antifungal, Antiparasitic and Antiviral drugs. Ed 6. London, UK: Hodder Arnold; 2010:1549–1553.
- Key JA. Positive pressure in arthrodesis for tuberculosis of the knee joint. 1932. Clin Orthop Relat Res. 2007;461:6–8. CrossRef
- Laine JC, Nguyen TQ, Buckley JM, Kim HT. Effects of mixing techniques on vancomycin-impregnated polymethylmethacrylate. J Arthroplasty. 2011;26:1562–1566. CrossRef
- Lange CG, Getty PJ, Morrissey AB, George AL, Young PC, Armitage KB. Destructive osteoarthritis after delayed diagnosis of tuberculosis. Infection. 2002;30:46–49. CrossRef
- Leclere LE, Sechriest VF 2nd, Holley KG, Tsukayama DT. Tuberculous arthritis of the knee treated with two-stage total knee arthroplasty: a case report. J Bone Joint Surg Am. 2009;91:186–191. CrossRef
- Martini M, Ouahes M. Bone and joint tuberculosis: a review of 652 cases. Orthopedics. 1988;11:861–866.
- Masri BA, Duncan CP, Jewesson P, Ngui-Yen J, Smith J. Streptomycin-loaded bone cement in the treatment of tuberculous osteomyelitis: an adjunct to conventional therapy. Can J Surg. 1995;38:64–68.
- Milovanova EM, Kovalenko KN. [Surgical correction of skeletal deformations in children with osteoarticular tuberculosis][in Russian]. Vestn Khir Im I I Grek. 1979;122:68–73.
- Mitchison DA. Clinical development of anti-tuberculosis drugs. J Antimicrob Chemother. 2006;58:494–495. CrossRef
- Mittal R, Trikha V, Rastogi S. Tuberculosis of patella. Knee. 2006;13:54–56. CrossRef
- Muradali D, Gold WL, Vellend H, Becker E. Multifocal osteoarticular tuberculosis: report of four cases and review of management. Clin Infect Dis. 1993;17:204–209. CrossRef
- Netval M, Hudec T, Hach J. [Our experience with total knee arthroplasty following tuberculous arthritis (1980–2005)][in Czech]. Acta Chir Orthop Traumatol Cech. 2007;74:111–113.
- Nuermberger E, Grosset J. Pharmacokinetic and pharmacodynamic issues in the treatment of mycobacterial infections. Eur J Clin Microbiol Infect Dis. 2004;23:243–255. CrossRef
- Pointud P, Prudat M, Laluque S, Amouroux J. [Tuberculous arthritis and chondrocalcinosis: apropos of 2 cases][in French]. Rev Rhum Ed Fr. 1993;60:617–620.
- Robson JM, Sullivan FM. Antituberculosis drugs. Pharmacol Rev. 1963;15:169–223.
- Senn N. Tuberculosis of Bones and Joints. Philadelphia, PA: FA Davis; 1893.
- Shikhare SN, Singh DR, Shimpi TR, Peh WC. Tuberculous osteomyelitis and spondylodiscitis. Semin Musculoskelet Radiol. 2011;15:446–458. CrossRef
- Su JY, Huang TL, Lin SY. Total knee arthroplasty in tuberculous arthritis. Clin Orthop Relat Res. 1996;323:181–187. CrossRef
- Titov AG, Nakonechniy GD, Santavirta S, Serdobintzev MS, Mazurenko SI, Konttinen YT. Arthroscopic operations in joint tuberculosis. Knee. 2004;11:57–62. CrossRef
- van Loenhout-Rooyackers JH, Verbeek AL, Jutte PC. Chemotherapeutic treatment for spinal tuberculosis. Int J Tuberc Lung Dis. 2002;6:259–265.
- Watts HG, Lifeso RM. Tuberculosis of bones and joints. J Bone Joint Surg Am. 1996;78:288–298.
- Weiner M, Burman W, Vernon A, Benator D, Peloquin CA, Khan A, Weis S, King B, Shah N, Hodge T. Low isoniazid concentrations and outcome of tuberculosis treatment with once-weekly isoniazid and rifapentine. Am J Respir Crit Care Med. 2003;167:1341–1347. CrossRef
- WHO. Stop TB Annual Report 2001. Geneva, Switzerland: World Health Organization; 2002. Available at: http://www.stoptb.org/assets/documents/resources/publications/annualreports/Final_report2001.pdf. Accessed January 25, 2013.
- WHO. Tuberculosis Fact sheet No 104. Geneva, Switzerland: World Health Organization; 2010. Available at: http://www.who.int/mediacentre/factsheets/fs104/en/index.html. Accessed January 25, 2013.
- Wilkinson MC. Synovectomy and curettage in the treatment of tuberculosis of joints. J Bone Joint Surg Br. 1953;35:209–223.
- Wolfgang GL. Tuberculosis joint infection. Clin Orthop Relat Res. 1978;136:257–263.
- Isoniazid Could Be Used for Antibiotic-loaded Bone Cement for Musculoskeletal Tuberculosis: An In Vitro Study
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Volume 471, Issue 7 , pp 2400-2406
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- 1. Department of Orthopaedic Surgery, Yonsei University College of Medicine, 134 Shinchon-dong, Seodaemun-gu, Seoul, 120-752, Korea
- 2. Department of Microbiology and Institute for Immunology and Immunological Diseases, Yonsei University College of Medicine, Seoul, Korea