Active Ingredient: Doxycycline
Between and, tigecycline retained activity against Gram-positive and Gram-negative organisms.
By contrast, the rate of vancomycin-resistant strains among Enterococcus faecium isolates almost doubled. Moreover, an increase in resistance to broad-spectrum beta-lactams and fluoroquinolones was observed for members of the family Enterobacteriaceae.
Against a background of a steadily rising number of pathogens that are resistant to various antibiotic classes, tigecycline represents an important treatment option.
In a second Tigecycline Evaluation Surveillance Trial conducted throughout Germany G-TEST II, the susceptibility of over 2,400 bacterial isolates, collected one year after the introduction of the new compound, was tested against tigecycline and comparators.
This study reports on the susceptibility of the isolates of 16 bacterial species and compares the results with those of a trial performed one year prior to the introduction of tigecycline G-TEST I. Data from the following bacterial species and groups were evaluated: Enterococcus faecalis.
Coagulase-negative staphylococci were only included in the study if they were recovered from at least two consecutive blood samples. Oral tetracycline treatment suppressed metalloproteinase activity in arthritic tissue, but even very high doses failed to exhibit substantial anti-inflammatory efficacy reduce joint swelling or paw diameter in adjuvant-induced arthritis of the rat Greenwald et al.
Clinical trials also proves its efficacy in arthritis Greenwald,; Golub et al.
However, it is a valuable tool to investigate the roles of arthritis-related MMPs in preclinical research. In our study, despite the predictable daily water consumption of the mice and reaching subantimicrobial plasma concentration Table 1, SDD did not inhibit either the in vivo MMP activity or the ex vivo activity of gelatinases derived from the arthritic ankle.
The latter result has been confirmed by incubating the arthritic joint homogenates with three different doxycycline concentrations according to the plasma levels measured from the SDD-treated animals. When testing higher, antimicrobial concentrations of doxycycline much above the highest plasma concentration measured in our study, only the highest concentration was able to significantly inhibit MMP-9, but not MMP-2 activity.
These results are in good accordance with similar data, which we obtained in lung and heart derived from mice chronically exposed to cigarette smoke, where SDD treatment did not alter MMP activity ex vivo.
However, in vitro treatment only with the highest plasma concentration measured from SDD-treated animals 0. Meanwhile, in the heart, none of the doxycycline concentrations decreased MMP-2 activity similarly to the joints unpublished data.
Although plasma doxycycline concentrations have been reliably determined, one limitation of this study is that we could not measure the tissue concentration of doxycycline in the joint homogenates due to technical difficulties.
In our study significant decrease of bone mineral density, which is also a hallmark clinical feature of human RA, was only demonstrated in the region of the distal tibia of SDD-treated mice.
Bone surface density only increased significantly in the distal tibia, which can be explained by the osteophyte-formation in this region.
Arthritis was accompanied by an increased trabecular connectivity in both distal tibia and ankle that is likely to reflect bone neoformation due to inflammation.
SDD treatment further significantly enhanced this parameter in both regions of arthritic mice as compared to their tap water consuming controls suggesting that SDD treatment results in detrimental overall effect as shown by aggravated periarticular bone resorption and reactive bone remodeling.
Previous studies have shown no effects of SDD on bone architecture under healthy conditions Fowlkes et al. Since Dkk-1 overexpressing mice display an osteopenic phenotype, and anti-Dkk-1 antibody treatment prevents bone loss in experimental OA, interference with these signaling pathways is likely to be involved in the increased trabecular connectivity observed in SDD-treated mice in our experiment Funck-Brentano et al.
SDD clearly worsens the chronic arthritis-induced bone microarchitectural alterations in a complex manner by simultaneously decreasing mineralization and increasing the trabecular connectivity.