Document Detail

In vitro activity of novel rifamycins against rifamycin-resistant Staphylococcus aureus.
MedLine Citation:
PMID:  16495239     Owner:  NLM     Status:  MEDLINE    
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.
Christopher K Murphy; Steve Mullin; Marcia S Osburne; John van Duzer; Jim Siedlecki; Xiang Yu; Kathy Kerstein; Michael Cynamon; David M Rothstein
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Publication Detail:
Type:  Comparative Study; In Vitro; Journal Article    
Journal Detail:
Title:  Antimicrobial agents and chemotherapy     Volume:  50     ISSN:  0066-4804     ISO Abbreviation:  Antimicrob. Agents Chemother.     Publication Date:  2006 Mar 
Date Detail:
Created Date:  2006-02-23     Completed Date:  2006-04-27     Revised Date:  2013-06-07    
Medline Journal Info:
Nlm Unique ID:  0315061     Medline TA:  Antimicrob Agents Chemother     Country:  United States    
Other Details:
Languages:  eng     Pagination:  827-34     Citation Subset:  IM    
ActivBiotics, Inc., 110 Hartwell Avenue, Lexington, Massachusetts 02421, USA.
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MeSH Terms
Drug Resistance, Bacterial
Molecular Conformation
Rifabutin / chemistry,  pharmacology*
Rifampin / chemistry,  pharmacology*
Rifamycins / chemistry,  pharmacology*
Staphylococcal Infections / drug therapy*
Staphylococcus aureus / drug effects*,  genetics
Reg. No./Substance:
0/Rifamycins; 129791-92-0/KRM 1648; 13292-46-1/Rifampin; 72559-06-9/Rifabutin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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