Concepts for increasing gentamicin release from handmade bone cement beads

Background and purpose Commercial gentamicin-loaded bone cement beads (Septopal) constitute an effective delivery system for local antibiotic therapy. These beads are not available in all parts of the world, and are too expensive for frequent use in others. Thus, orthopedic surgeons worldwide make antibiotic-loaded beads themselves. However, these beads are usually not as effective as the commercial beads because of inadequate release kinetics. Our purpose was to develop a simple, cheap, and effective formulation to prepare gentamicin-loaded beads with release properties and antibacterial efficacy similar to the commercially ones. Methods Acrylic beads were prepared with variable monomer content: 100% (500 μL/g polymer), 75%, and 50% to increase gentamicin release through creation of a less dense polymer matrix. Using the optimal monomer content, different gel-forming polymeric fillers were added to enhance the permeation of fluids into the beads. Polyvinylpyrrolidone (PVP) 17 was selected as a suitable filler; its concentration was varied and the antibiotic release and antibacterial efficacy of these beads were compared with the corresponding properties of the commercial ones. Results Gentamicin release rate and the extent of release from beads prepared with 50% monomer increased when the PVP17 content was increased. Beads with 15 w/w% PVP17 released 87% of their antibiotic content. This is substantially more than the gentamicin release from Septopal beads (59%). Acrylic beads with 15 w/w% PVP17 reduced bacterial growth by up to 93%, which is similar to the antibacterial properties of the commercial ones. Interpretation A simple, cheap, and effective formulation and preparation process has been described for hand-made gentamicin-releasing acrylic beads, with better release kinetics and with antibacterial efficacy similar to that of the commercial ones

Accepting higher morbidity in exchange for sacrificing fewer animals in studies developing novel infection-control strategies.

Preventing bacterial infections from becoming the leading cause of death by the year 2050 requires the development of novel, infection-control strategies, building heavily on biomaterials science, including nanotechnology. Pre-clinical (animal) studies are indispensable for this development. Often, animal infection outcomes bear little relation to human clinical outcome. Here, we review conclusions from pathogen-inoculum dose-finding pilot studies for evaluation of novel infection-control strategies in murine models. Pathogen-inoculum doses are generally preferred that produce the largest differences in quantitative infection outcome parameters between a control and an experimental group, without death or termination of animals due to having reached an inhumane end-point during the study. However, animal death may represent a better end-point for evaluation than large differences in outcome parameters or number of days over which infection persists. The clinical relevance of lower pre-clinical outcomes, such as bioluminescence, colony forming units (CFUs) retrieved or more rapid clearance of infection is unknown, as most animals cure infection without intervention, depending on pathogen-species and pathogen-inoculum dose administered. In human clinical practice, patients suffering from infection present to hospital emergency wards, frequently in life-threatening conditions. Animal infection-models should therefore use prevention of death and recurrence of infection as primary efficacy targets to be addressed by novel strategies. To compensate for increased animal morbidity and mortality, animal experiments should solely be conducted for pre-clinical proof of principle and safety. With the advent of sophisticated in vitro models, we advocate limiting use of animal models when exploring pathogenesis or infection mechanisms

Atomic force microscopy study on specificity and non-specificity of interaction forces between Enterococcus faecalis cells with and without aggregation substance

Enterococcus faecalis is one of the leading causes of hospital-acquired infections, and indwelling medical devices are especially prone to infection. E faecalis expressing aggregation substance (Agg) adheres to biomaterial surfaces by means of positive cooperativity, i.e. the ability of one adhering organism to stimulate adhesion of other organisms in its immediate vicinity. In this study, atomic force microscopy (AFM) was used to measure the specificity and non-specificity of interaction forces between E faecalis cells with and without Agg. Bacteria were attached to a substratum surface and a tip-less cantilever. Two E faecalis strains expressing different forms of Agg showed nearly twofold higher interaction forces between bacterial cells than a strain lacking Agg [adhesive force (F-adh), -1(.)3 nN]. The strong interaction forces between the strains with Agg were reduced after adsorption of antibodies against Agg from -2(.)6 and -2(.)3 nN to -1(.)2 and -1.3 nN, respectively. This suggests that the non-specific interaction force between the enterococci amounts to approximately 1(.)2 nN, while the specific force component is only twofold stronger. Comparison of the results of the AFM interaction forces with the positive cooperativity after adhesion to a biomaterial in a parallel-plate flow chamber showed that in the absence of strong interaction forces between the cells, positive cooperativity was also absent. In conclusion, this is believed to be the first time that the influence of specific antibodies on interaction forces between E faecalis cells has been demonstrated by AFM, thereby experimentally distinguishing between specific and non-specific force components

Surface free energies and the adhesion of oral bacteria

Caries en parodontale ontstekingen worden beschouwd als te behoren tot twee van de meest wijd verspreide ziekten ter wereld. Caries en parodontale ontstekingen ontstaan ten gevolge van bakteriele hechting aan het tandoppervlak. Het is tot op heden niet volledig begrepen, hoe en door welk mechanisme bakterien aan vaste stof oppervlakken hechten. ... Zie: Samenvatting

Weibull analyses of bacterial interaction forces measured using AFM

Statistically significant conclusions from interaction forces obtained by AFM are difficult to draw because of large data spreads. Weibull analysis, common in macroscopic bond-strength analyses, takes advantage of this spread to derive a Weibull distribution, yielding the probability of occurrence of a force value and the dependability of the data set. Here we propose Weibull distribution as a new way to present nanoscopic bacterial interaction forces obtained using AFM. (C) 2010 Elsevier B.V. All rights reserved