In vitro and in vivo antimicrobial activity of sodium colistimethate and amikacin-loaded nanostructured lipid carriers (NLC).

Sodium colistimethate (SCM) and amikacin (AMK) are among the few antibiotics effective against resistant P. aeruginosa, K. pneumoniae and A. baumannii; however, their toxicity severely limits their use. Enclosing antibiotics into nanostructured lipid carriers (NLC) might decrease drug toxicity and improve antibiotic disposition. In this work, SCM or AMK was loaded into different NLC formulations, through high pressure homogenization, and their in vitro and in vivo effectiveness was analyzed. The encapsulation process did not reduce drug effectiveness since in vitro SCM-NLC and AMK-NLC drug activity was equal to that of the free drugs. As cryoprotectant, trehalose showed better properties than dextran. Instead, positive chitosan coating was discarded due to its limited cost-efficiency. Finally, the in vivo study in acute pneumonia model revealed that intraperitoneal administration was superior to the intramuscular route and confirmed that (-) SCM-NLC with trehalose, was the most suitable formulation against an extensively drug-resistant A. baumannii strain.

Preclinical safety of topically administered nanostructured lipid carriers (NLC) for wound healing application: biodistribution and toxicity studies.

Re-activation of the healing process is a major challenge in the field of chronic wound treatment. For that purpose, lipid-nanoparticles, especially nanostructured lipid carriers (NLC), possess extremely useful characteristics such as biodegradability, biocompatibility and long-term stability, besides being suitable for drug delivery. Moreover, they maintain wound moisture due to their occlusive properties, which have been associated with increased healing rates. In the light of above, NLC have been extensively used topically for wound healing; but to date, there are no safety-preclinical studies concerning such type of application. Thus, in this work, biodistribution studies were performed in rats with the NLC previously developed by our research group, using technetium-99 m (99mTc-NLC) as radiomarker, topically administered on a wound. 99mTc-NLC remained on the wound for 24 h and systemic absorption was not observed after administration. In addition, toxicological studies were performed to assess NLC safety after topical administration. The results obtained demonstrated that NLC were non-cytotoxic, non-sensitizing and non-irritant/corrosive. Overall, it might be concluded that developed NLC remained at the administration area, potentially exerting a local effect, and were safe after topical administration on wounds.

In vitro activity of linezolid in combination with doxycycline, fosfomycin, levofloxacin, rifampicin and vancomycin against methicillin-susceptible Staphylococcus aureus.

The objective of this paper was to investigate the in vitro effects of linezolid combined with five antistaphylococcal antibiotics--doxycycline, fosfomycin, levofloxacin, rifampicin and vancomycin--upon methicillin-susceptible Staphylococcus aureus (MSSA). Five MSSA isolates from clinical specimens of human infections--hf008, hf095, hf295, hf602 and hf946--were used in this study. The checkerboard method was used to assess synergism between linezolid and the five antibiotics, and time-kill curves were carried out with the most active combinations. Indifference was the most common result achieved by the checkerboard method when linezolid was combined with rifampicin, vancomycin or doxycycline. The combination with levofloxacin yielded antagonism for two of the five isolates. However, four isolates showed synergy for the combination of linezolid plus fosfomycin with a fractional inhibitory concentration index (FICI) > or = 0.5. Neither linezolid nor fosfomycin alone inhibited growth at 1/4x minimum inhibitory concentration (MIC); but the combination of both drugs at 1/4 the respective MIC showed a synergistic bacteriostatic effect, a 2-3 log(10) decrease with respect to the most active antibiotic alone. In summary, the combination of subinhibitory.

Tuberculosis extrapulmonar. Analisis de 450 casos. / Extrapulmonary tuberculosis. Analysis of 450 cases

Se comenta la experiencia recogida del analisis de 450 casos de tuberculosis extrapulmonar, que por trabajar en un hospital general integrado al programa de control de la tuberculosis y contar con los medios de diagnostico y seguimiento necesarios pudimos comprobar en el termino de nueve anos(1973-1981). Se destaca en especial la metodologia seguida en la confirmacion diagnostica, efectuando un juicio critico de la misma. El estudio histopatologico y el cultivo del material obtenido por biopsia han sido los metodos de eleccion en nuestra experiencia y por ello los propiciamos