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Penetration of linezolid into rabbit intervertebral discs and surrounding tissues

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Abstract

Linezolid belongs to a new class of synthetic antimicrobial agent that is effective for a variety of methicillin-resistant Staphylococcus aureus (MRSA) infections including bone and joint MRSA infections, but the effectiveness of linezolid for the treatment of MRSA spine infection remains controversial. In this study, we investigated the diffusion of linezolid or vancomycin into normal rabbit spinal tissues to determine the adequacy of linezolid for the treatment of spinal infection. The penetration efficacy of linezolid into the annulus fibrosus, nucleus pulposus, and vertebral bone (10, 8, and 10%, respectively) was lower than that of vancomycin (27, 11, and 14%, respectively). The penetration efficacy of linezolid into the bone marrow and iliopsoas muscle (88 and 84%, respectively), however, was higher than that of vancomycin (67 and 9%, respectively). These results suggest that linezolid is inadequate for the treatment of spine infection limited to the intervertebral disc, but may be effective for the treatment of infection extending into the muscle and bone marrow, such as in vertebral osteomyelitis, iliopsoas abscess, and postsurgical infection.

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References

  1. Centers for Disease Control, Prevention (CDC) (2002) Staphylococcus aureus resistant to vancomycin–United States, 2002. MMWR Morb Mortal Wkly Rep 26:565–567

    Google Scholar 

  2. Acosta FL, Galvez LF Jr, Aryan HE, Ames CP (2006) Recent advances: infections of the spine. Curr Infect Dis Rep 5:390–393

    Article  Google Scholar 

  3. Al-Nammari SS, Lucas JD, Lam KS (2007) Hematogenous methicillin-resistant Staphylococcus aureus spondylodiscitis. Spine 32:2480–2486

    Article  PubMed  Google Scholar 

  4. Bassetti M, Vitale F, Melica G, Righi E, Di Biagio A, Molfetta L, Pipino F, Cruciani M, Bassetti D (2005) Linezolid in the treatment of Gram-positive prosthetic joint infections. J Antimicrob Chemother 3:387–390. doi:10.1093/jac/dki016

    Article  Google Scholar 

  5. Carragee EJ (1997) Pyogenic vertebral osteomyelitis. J Bone Joint Surg Am 6:874–880

    Google Scholar 

  6. Conaughty JM, Chen J, Martinez OV, Chiappetta G, Brookfield KF, Eismont FJ (2006) Efficacy of linezolid versus vancomycin in the treatment of methicillin-resistant Staphylococcus aureus discitis: a controlled animal model. Spine 22:E830–E832. doi:10.1097/01.brs.0000242943.62880.3f

    Article  Google Scholar 

  7. Cottagnoud P, Gerber CM, Acosta F, Cottagnoud M, Neftel K, Tauber MG (2000) Linezolid against penicillin-sensitive and -resistant pneumococci in the rabbit meningitis model. J Antimicrob Chemother 6:981–985

    Article  Google Scholar 

  8. Currier BL, Banovac K, Eismont FJ (1994) Gentamicin penetration into normal rabbit nucleus pulposus. Spine 23:2614–2618

    Google Scholar 

  9. Fang A, Hu SS, Endres N, Bradford DS (2005) Risk factors for infection after spinal surgery. Spine 12:1460–1465. doi:10.1097/01.brs.0000166532.58227.4f

    Article  Google Scholar 

  10. Farin D, Piva GA, Gozlan I, Kitzes-Cohen R (1998) A modified HPLC method for the determination of vancomycin in plasma and tissues and comparison to FPIA (TDX). J Pharm Biomed Anal 3:367–372. doi:10.1016/S0731-7085(98)00095-8

    Article  Google Scholar 

  11. Gasbarrini AL, Bertoldi E, Mazzetti M, Fini L, Terzi S, Gonella F, Mirabile L, Barbanti Brodano G, Furno A, Gasbarrini A, Boriani S (2005) Clinical features, diagnostic and therapeutic approaches to haematogenous vertebral osteomyelitis. Eur Rev Med Pharmacol Sci 1:53–66

    Google Scholar 

  12. Graziani AL, Lawson LA, Gibson GA, Steinberg MA, MacGregor RR (1988) Vancomycin concentrations in infected and noninfected human bone. Antimicrob Agents Chemother 9:1320–1322

    Google Scholar 

  13. Guiboux JP, Cantor JB, Small SD, Zervos M, Herkowitz HN (1995) The effect of prophylactic antibiotics on iatrogenic intervertebral disc infections: a rabbit model. Spine 6:685–688

    Article  Google Scholar 

  14. Hadjipavlou AG, Mader JT, Necessary JT, Muffoletto AJ (2000) Hematogenous pyogenic spinal infections and their surgical management. Spine 25:1668–1679

    Article  CAS  PubMed  Google Scholar 

  15. Honeybourne D, Tobin C, Jevons G, Andrews J, Wise R (2003) Intrapulmonary penetration of linezolid. J Antimicrob Chemother 6:1431–1434

    Article  Google Scholar 

  16. Johnson KD, Johnston DW (1986) Orthopedic experience with methicillin-resistant Staphylococcus aureus during a hospital epidemic. Clin Orthop Relat Res 212:281–288

    PubMed  Google Scholar 

  17. Lovering AM, Zhang J, Bannister GC, Lankester BJ, Brown JH, Narendra G, MacGowan AP (2002) Penetration of linezolid into bone, fat, muscle and haematoma of patients undergoing routine hip replacement. J Antimicrob Chemother 1:73–77

    Article  Google Scholar 

  18. Manfredi R, Sabbatani S, Chiodo F (2005) Severe staphylococcal knee arthritis responding favourably to linezolid, after glycopeptide-rifampicin failure: a case report and literature review. Scand J Infect Dis 6–7:513–517. doi:10.1080/00365540510036589

    Article  Google Scholar 

  19. Massias L, Dubois C, de Lentdecker P, Brodaty O, Fischler M, Farinotti R (1992) Penetration of vancomycin in uninfected sternal bone. Antimicrob Agents Chemother 11:2539–2541

    Google Scholar 

  20. McHenry MC, Easley KA, Locker GA (2002) Vertebral osteomyelitis: long-term outcome for 253 patients from 7 Cleveland-area hospitals. Clin Infect Dis 10:1342–1350

    Article  Google Scholar 

  21. Peng GW, Stryd RP, Murata S, Igarashi M, Chiba K, Aoyama H, Aoyama M, Zenki T, Ozawa N (1999) Determination of linezolid in plasma by reversed-phase high-performance liquid chromatography. J Pharm Biomed Anal 1–2:65–73. doi:10.1016/S0731-7085(98)00310-0

    Article  Google Scholar 

  22. Rana B, Butcher I, Grigoris P, Murnaghan C, Seaton RA, Tobin CM (2002) Linezolid penetration into osteo-articular tissues. J Antimicrob Chemother 5:747–750

    Article  Google Scholar 

  23. Rayner CR, Baddour LM, Birmingham MC, Norden C, Meagher AK, Schentag JJ (2004) Linezolid in the treatment of osteomyelitis: results of compassionate use experience. Infection 1:8–14. doi:10.1007/s15010-004-3029-9

    Google Scholar 

  24. Rezai AR, Woo HH, Errico TJ, Cooper PR (1999) Contemporary management of spinal osteomyelitis. Neurosurgery 5:1018–1025 discussion 1025-1016

    Article  Google Scholar 

  25. Riley LH, Banovac K 3rd, Martinez OV, Eismont FJ (1994) Tissue distribution of antibiotics in the intervertebral disc. Spine 23:2619–2625

    Google Scholar 

  26. Scuderi GJ, Greenberg SS, Banovac K, Martinez OV, Eismont FJ (1993) Penetration of glycopeptide antibiotics in nucleus pulposus. Spine 14:2039–2042

    Article  Google Scholar 

  27. Slatter JG, Adams LA, Bush EC, Chiba K, Daley-Yates PT, Feenstra KL, Koike S, Ozawa N, Peng GW, Sams JP, Schuette MR, Yamazaki S (2002) Pharmacokinetics, toxicokinetics, distribution, metabolism and excretion of linezolid in mouse, rat and dog. Xenobiotica 10:907–924

    Article  Google Scholar 

  28. Srinivasan A, Dick JD, Perl TM (2002) Vancomycin resistance in staphylococci. Clin Microbiol Rev 3:430–438. doi:10.1128/CMR.15.3.430-438.2002

    Article  Google Scholar 

  29. Tobin CM, Sunderland J, White LO, MacGowan AP (2001) A simple, isocratic high-performance liquid chromatography assay for linezolid in human serum. J Antimicrob Chemother 5:605–608

    Article  Google Scholar 

  30. Urban JP, Smith S, Fairbank JC (2004) Nutrition of the intervertebral disc. Spine 23:2700–2709. doi:10.1097/01.brs.0000146499.97948.52

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Orthopaedic Surgery, Hokkaido University Graduate School of Medicine, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    Miki Komatsu, Masahiko Takahata, Manabu Ito, Yuichiro Abe, Tohru Irie, Norimasa Iwasaki & Akio Minami

  2. Department of Pharmacy, Hokkaido University Hospital, Kita-15 Nishi-7, Kita-ku, Sapporo, 060-8638, Japan

    Mitsuru Sugawara

  3. Laboratory of Pharmacotherapeutic Information, Department of Biopharmaceutical Sciences and Pharmacy, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo, 060-8638, Japan

    Yoh Takekuma & Takashi Kato

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  1. Miki Komatsu
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  2. Masahiko Takahata
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Correspondence to Masahiko Takahata.

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Komatsu, M., Takahata, M., Sugawara, M. et al. Penetration of linezolid into rabbit intervertebral discs and surrounding tissues. Eur Spine J 19, 2149–2155 (2010). https://doi.org/10.1007/s00586-010-1548-x

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  • DOI: https://doi.org/10.1007/s00586-010-1548-x

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