Estudio experimental de la aplicación de un nuevo cemento óseo cargado con antibióticos de amplio espectro para el tratamiento de la infección ósea / Experimental study of the application of a new bone cement loaded with broad spectrum antibiotics for the treatment of bone infection

Objetivos: Valorar el comportamiento histológico, en un modelo animal de conejo, de un nuevo cemento óseo modificado, el cual aumenta la liberación local de antibiótico, en la infección ósea. Material y métodos: Se han utilizado 16 conejos Nueva Zelanda divididos en 4 grupos, en función del cemento (comercial o experimental) y del antibiótico (vancomicina o linezolid) empleados para controlar una infección ósea por Staphylococcus aureus. El cemento comercial es Palacos(R) R y el cemento experimental se ha conseguido añadiendo PLGA a la fase sólida del cemento Palacos(R) R. Se ha empleado un método de estadificación histológica novedoso, basado en la histoarquitectura ósea. Esta estadificación nos permite tener una visión global de la capacidad de reparación ósea, en presencia del cemento modificado, así como correlacionar el daño generado con la funcionalidad del tejido. Resultados: El grado de desestructuración ósea encontrado depende del tipo de cemento y del antibiótico, siendo mayor en los grupos con cemento comercial respecto al experimental (p<0,01) y en los grupos con linezolid respecto a vancomicina (p=0,04). El porcentaje de macrófagos varía exclusivamente en función del antibiótico utilizado, siendo mayor en los grupos con vancomicina respecto a linezolid (p=0,04). Discusión: El desarrollo de nuevas formulaciones de cemento óseo que liberan mayor cantidad, y de forma más prolongada, de antibióticos de nueva generación como el linezolid presentan un comportamiento in vivo superior al cemento comercial, respetando más la estructura ósea. Este comportamiento tendría una implicación clínica para combatir las infecciones por gérmenes cada vez más resistentes y prevenir la colonización de los espaciadores de cemento usados habitualmente en el tratamiento de la infección protésica

Objectives: To evaluate the in vivo behaviour of a new bone cement loaded with antibiotics, in a rabbit bone infection model. Material and methods: Sixteen New Zealand rabbits divided into 4 groups were used, depending on the cement (commercial or experimental) and the antibiotic (vancomycin or linezolid) used to control a bone infection caused by Staphylococcus aureus. The commercial cement is Palacos(R) R and the experimental cement has been achieved by adding PLGA to the solid phase of Palacos(R) R cement. A novel histological staging method based on bone histoarchitecture has been used. This staging allows us a global vision of bone repair capacity, in the presence of modified cement, and also allows us to correlate the damage generated with the functionality of the tissue. Results: The degree of bone destructuration found depended on the type of cement and antibiotic, and was higher in the groups with commercial cement than in the experimental group (P<.01) and in the groups with linezolid with respect to vancomycin (P=.04) The percentage of macrophages varied exclusively depending on the antibiotic used, and was higher in the vancomycin groups (P=.04). Discussion: The development of new formulations of bone cement that release more, and more prolonged, new generation antibiotics such as linezolid, present an in vivo behaviour superior to commercial cement, respecting the bone structure. This behaviour would have a clinical implication in fighting infections by increasingly resistant germs in the treatment of prosthetic infection

Experimental study of the application of a new bone cement loaded with broad spectrum antibiotics for the treatment of bone infection. / Estudio experimental de la aplicación de un nuevo cemento óseo cargado con antibióticos de amplio espectro para el tratamiento de la infección ósea.

OBJECTIVES: To evaluate the in vivo behaviour of a new bone cement loaded with antibiotics, in a rabbit bone infection model. MATERIAL AND METHODS: Sixteen New Zealand rabbits divided into 4 groups were used, depending on the cement (commercial or experimental) and the antibiotic (vancomycin or linezolid) used to control a bone infection caused by Staphylococcus aureus. The commercial cement is Palacos® R and the experimental cement has been achieved by adding PLGA to the solid phase of Palacos® R cement. A novel histological staging method based on bone histoarchitecture has been used. This staging allows us a global vision of bone repair capacity, in the presence of modified cement, and also allows us to correlate the damage generated with the functionality of the tissue. RESULTS: The degree of bone destructuration found depended on the type of cement and antibiotic, and was higher in the groups with commercial cement than in the experimental group (P<.01) and in the groups with linezolid with respect to vancomycin (P=.04) The percentage of macrophages varied exclusively depending on the antibiotic used, and was higher in the vancomycin groups (P=.04). DISCUSSION: The development of new formulations of bone cement that release more, and more prolonged, new generation antibiotics such as linezolid, present an in vivo behaviour superior to commercial cement, respecting the bone structure. This behaviour would have a clinical implication in fighting infections by increasingly resistant germs in the treatment of prosthetic infection.

Development of advanced biantibiotic loaded bone cement spacers for arthroplasty associated infections.

The incidence increase of infections in patients with hip or knee implants with resistant pathogens (mainly some S. coagulase-negative and gram positive bacteria) demands advanced antibiotic loaded formulations. In this paper, we report the design of new biantibiotic acrylic bone cements for in situ delivery. They include a last generation antibiotic (daptomycin or linezolid) in combination with vancomycin and are performed based on a novel modification of the Palacos R® acrylic bone cement, which is based on two components, a liquid (methyl methacrylate) and a solid (polymeric phase). Hence, the solid component of the experimental formulations include 45wt% of microparticles of poly(D,L-lactic-co-glycolic) acid, 55wt% of poly(methyl methacrylate) beads and supplements (10wt-% each) of antibiotics. These formulations provide a selective and excellent control of the local release of antibiotics during a long time period (up to 2 months), avoiding systemic dissemination. The antimicrobial activity of the advanced spacers tested against S. aureus shows that single doses would be enough for the control of the infection. In vitro biocompatibility of cements on human osteoblasts is ensured. This paper is mainly focused on the preparation and characterization of cements and the studies of elution kinetics and bactericidal effects. Developed formulations are proposed as spacers for the treatment of infected arthroplasties, but also, they could be applied in other antibiotic devices to treat relevant bone-related infection diseases.