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Etude PK/PD du linézolide et de la daptomycine et intérêt de l'IRM associée aux USPIOS dans deux modèles d'infections expérimentales à Staphylococcus aureus chez le lapin : endophtalmie et arthrite aiguës

Abstract : Staphylococcus aureus (S. aureus) is a frequent cause of acute endophthalmitis and arthritis in humans. In the first part, we investigated the ocular pharmacodynamics and safety of two recently approved antistaphylcoccal antibiotics, linezolid and daptomycin. Only a very high intravitreal dose of linezolid (30 mg / 0.1 mL) showed a bactericidal and clinical efficacy. Suchintraocular concentrations appeared to be safe for the retinal function, and linezolide could be considered as a promising therapeutic alternative. The effective intravitreal dose of daptomycin (1 mg / 0.1 mL) was responsible for a significant impairment of the functional integrity of the retina. Finally, the ocular pharmacodynamics of these two antibiotics showed special features in comparison with the one of other types of tissue infection. In a second part, we evaluated a newimaging method in experimental infectious arthritis, by using MRI enhanced by ultrasmall superparamagnetic iron oxide (USPIO). We first showed this method can depict the macrophage infiltration in infected synovium, and secondly it can demonstrate resolution of joint infection, in contrast to conventional MRI performed by gadolinium chelates. This in vivo non invasive imaging method therefore presents a new dimension in musculoskeletal imaging by accurately helping monitor bacterial joint infection.
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Sophie Lefevre. Etude PK/PD du linézolide et de la daptomycine et intérêt de l'IRM associée aux USPIOS dans deux modèles d'infections expérimentales à Staphylococcus aureus chez le lapin : endophtalmie et arthrite aiguës. Médecine humaine et pathologie. Université de Strasbourg, 2012. Français. ⟨NNT : 2012STRAJ095⟩. ⟨tel-00866338⟩

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