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Invivo assessment of activity of calcium-deficient apatite linezolid drug delivery system versus systemic administration of linezolid in a rabbit osteomyelitis experimental model due to MRSA

Abstract number: P1559

Gaudin A., Amador G., Gautier H., Le Mabecque V., Miegeville A.F., Potel G., Bouler J.M., Weiss P., Caillon J., Jacqueline C.

Background: Linezolid is considered as an alternative to vancomycin for severe osseous infections. Calcium-deficient apatites (CDA) can be associated with therapeutic agents such as linezolid to form drug-delivery systems. The aim of this work was to evaluate the in vivo activity of linezolid adsorbed onto CDA microparticles in addition to standard treatments.

Methods: Femoral trepanation of rabbits was performed, followed by injection of 109 CFU MRSA (linezolid MIC = 2 mg/mL) suspension into the knee cavity. A surgical debridement of the infected tissues was performed 3 days later and animals were randomly assigned to: V(iv) (vancomycin constant IV infusion to reach a 20×MIC serum steady-state concentration), L(iv) (10 mg/kg/12 h IV infusion), CDA (osseous gap filled with 100 mg CDA), L(CDA) (100 mg CDA with linezolid 10 mg/mg) and L(CDA)+ L(iv) (100 mg CDA with linezolid 10 mg/mg filling in addition to 10 mg/kg/12 h IV infusion). Surviving bacteria were counted in joint fluid (JF), bone marrow (BM) and bone (BO) at days 3 and 7 (4-day treatment).

Results: See graphic.

Conclusions: (1) V(iv) was ineffective against MRSA after a 4-day treatment. (2) CDA alone showed no in vivo antibacterial activity. (3) CDA as linezolid drug delivery (L(CDA)) system demonstrated significant in vivo activity in BM and BO, in this model, as compared to vancomycin. (4) L(CDA) + L(iv) treatment did not exhibit a greater efficacy in the three compartments than L(CDA) alone.

TreatmentnMean±SD delta log10 CFU/g of tissue (day 7 - day 3)
  JFBMBO
V(iv)5-0.03±0.93-0.73±1.84-0.61±0.76
L(iv)5-0.77±1.32-2.69±2.00*-2.25±1.63*
CDA5-0.49±0.320.56±0.310.22±0.25
L(CDA)5-0.80±1.11-2.56±1.48*-1.18±0.86**
L(CDA) + L(iv)5-1.21±0.30-3.51±0.43*-1.85±0.95**
n: number of animals; *P < 0.05 vs V(iv) and CDA; **P < 0.05 vs CDA. Student–Newman–Keuls test after ANOVA.

Session Details

Date: 10/04/2010
Time: 00:00-00:00
Session name: Abstracts 20th European Congress of Clinical Microbiology and Infectious Diseases
Subject:
Location: Vienna, Austria, 10 - 13 April 2010
Presentation type:
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