Activity and Diffusion of LY333328 in Experimental Endocarditis Due to Vancomycin-Resistant Enterococcus faecalis
AUTOR(ES)
Saleh-Mghir, Azzam
FONTE
American Society for Microbiology
RESUMO
The activity of LY333328 against Enterococcus faecalis JH2-2, which is susceptible to glycopeptides, and against its transconjugants E. faecalis BM4281 and BM4316, with VanB and VanA phenotypes, respectively, was investigated. LY333328 was active in vitro against the three strains, for which MICs were 2 μg/ml on agar and 0.25 μg/ml in broth. LY333328 was bactericidal in broth against E. faecalis JH2-2 and BM4281 at a concentration of 8 μg/ml and against BM4316 at a concentration of 30 μg/ml. The protein binding of LY333328 to rabbit serum was >99%, and the bactericidal activity of LY333328 in broth was reduced when it was tested in the presence of 90% rabbit serum. Autoradiographic studies performed in rabbits with enterococcal endocarditis showed that 14[C]LY333328 was distributed heterogeneously throughout cardiac vegetations. In rabbits with aortic endocarditis, a regimen of 20 mg of LY333328 per kg of body weight administered intramuscularly twice a day for 5 days after a loading dose of 40 mg/kg was active against the three strains in vivo (P < 0.01), whereas vancomycin was not active against the VanB-type strain and teicoplanin was not active against the VanA-type strain. We conclude that the activity of LY333328 is not significantly modified by acquired resistance to glycopeptides in E. faecalis either in vitro or in experimental endocarditis.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=89030Documentos Relacionados
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