1. A delivery system of linezolid to enhance the MRSA osteomyelitis prognosis: in vivo experimental assessment
- Author
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Pierre Weiss, Gilles Potel, Jocelyne Caillon, Alexis Gaudin, Anne-Françoise Miègeville, Jean-Michel Bouler, Gilles Amador, V. Le Mabecque, H. Gautier, Cyndie Desessard, Cédric Jacqueline, Thérapeutiques cliniques et expérimentales des infections (EA 3826) (EA 3826), Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN), Laboratoire d'ingénierie osteo-articulaire et dentaire (LIOAD), Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), and Jehan, Frederic
- Subjects
Antibiotics ,Colony Count, Microbial ,02 engineering and technology ,medicine.disease_cause ,Gastroenterology ,chemistry.chemical_compound ,Drug Delivery Systems ,Bone Marrow ,Apatites ,Acetamides ,[SDV.MHEP.RSOA] Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,0303 health sciences ,[SDV.MHEP.GEG] Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,[SDV.MHEP.GEG]Life Sciences [q-bio]/Human health and pathology/Geriatry and gerontology ,Osteomyelitis ,General Medicine ,Staphylococcal Infections ,021001 nanoscience & nanotechnology ,Glycopeptide ,Anti-Bacterial Agents ,3. Good health ,Treatment Outcome ,Infectious Diseases ,medicine.anatomical_structure ,[SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system ,Staphylococcus aureus ,Female ,Rabbits ,0210 nano-technology ,Methicillin-Resistant Staphylococcus aureus ,Microbiology (medical) ,medicine.medical_specialty ,medicine.drug_class ,Bone and Bones ,Bone Infection ,03 medical and health sciences ,Minimum inhibitory concentration ,Internal medicine ,medicine ,Animals ,Oxazolidinones ,030306 microbiology ,business.industry ,Linezolid ,medicine.disease ,Surgery ,Disease Models, Animal ,chemistry ,Bone marrow ,business - Abstract
International audience; Staphylococcusaureus, 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 Staphylococcusaureus (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 bonemarrow (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 log[10]CFU/g decrease of −2.63±1.92 and −2.17±1.58 in bone marrowand bone, respectively. CDA loaded with linezolid enhance the efficacy of the IV linezolid regimen by more than one log[10]CFU/g.
- Published
- 2012
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