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Antimicrob Agents Chemother ; 50(3): 827-34, 2006 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-16495239

RESUMO

We describe novel rifamycin derivatives (new chemical entities [NCEs]) that retain significant activity against a comprehensive collection of Staphylococcus aureus strains that are resistant to rifamycins. This collection of resistant strains contains 21 of the 26 known single-amino-acid alterations in RpoB, the target of rifamycins. Some NCEs also demonstrated a lower frequency of resistance development than rifampin and rifalazil in S. aureus as measured in a resistance emergence test. When assayed for activity against the strongest rifamycin-resistant mutants, several NCEs had MICs of 2 microg/ml, in contrast to MICs of rifampin and rifalazil, which were 512 microg/ml for the same strains. The properties of these NCEs therefore demonstrate a significant improvement over those of earlier rifamycins, which have been limited primarily to combination therapy due to resistance development, and suggest a potential use of these NCEs for monotherapy in several clinical indications.


Assuntos
Rifabutina/farmacologia , Rifampina/farmacologia , Rifamicinas/farmacologia , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Farmacorresistência Bacteriana , Técnicas In Vitro , Conformação Molecular , Rifabutina/química , Rifampina/química , Rifamicinas/química , Staphylococcus aureus/genética
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