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A delivery system of linezolid to enhance the MRSA osteomyelitis prognosis: in vivo experimental assessment

  • A. Gaudin
  • C. Jacqueline
  • H. Gautier
  • C. Desessard
  • V. Le Mabecque
  • A.-F. Miegeville
  • G. Potel
  • J.-M. Bouler
  • P. Weiss
  • J. Caillon
  • G. AmadorEmail author
Article

Abstract

Staphylococcus aureus, a major responsible microorganism of osteomyelitis, represents a challenge to treat because of the poor penetration of antibiotics in bone and increasing minimum inhibitory concentrations (MICs) to glycopeptides. The calcium-deficient apatites (CDA), closer to the biological components found in bone and other calcified tissues, have osteoconductive properties. So, to process severe osseous infections, CDA can be used to deliver in the infectious site antibiotics like linezolid. The acute experimental osteomyelitis due to methicillin-resistant Staphylococcus aureus (MRSA) was induced in rabbit’s femurs and surgery mimicking human procedures was performed at day three after inoculation. Animals were randomly assigned to treatment groups: L(IV) [4-day linezolid IV infusion, human-equivalent dose of 10 mg/kg/12 h], L(CDA50%) (100 mg CDA with linezolid 500 μg/mg) and L(CDA50%) + L(IV). Surviving bacteria were counted in bone marrow (BM) and bone (Bo) at day 3 (before treatment), day 7 (4-day treatment) or day 17 (14-day treatment). L(iv) was effective after a 4-day treatment with a log10CFU/g decrease of −2.63 ± 1.92 and −2.17 ± 1.58 in bone marrow and bone, respectively. CDA loaded with linezolid enhance the efficacy of the IV linezolid regimen by more than one log10CFU/g.

Keywords

Minimum Inhibitory Concentration Osteomyelitis Linezolid Bacterial Count Bone Infection 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Conflict of interest

The authors declare that they have no conflict of interest.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • A. Gaudin
    • 1
  • C. Jacqueline
    • 1
    • 3
  • H. Gautier
    • 2
  • C. Desessard
    • 1
  • V. Le Mabecque
    • 1
  • A.-F. Miegeville
    • 1
  • G. Potel
    • 1
    • 3
  • J.-M. Bouler
    • 2
  • P. Weiss
    • 2
  • J. Caillon
    • 1
    • 3
  • G. Amador
    • 1
    • 3
    Email author
  1. 1.Faculté de Médecine, UPRES EA 3826Université de NantesNantesFrance
  2. 2.INSERM UMRS 791, Laboratory of Osteoarticular and Dental Tissue EngineeringNantesFrance
  3. 3.CHU NantesNantesFrance

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