Document Detail

Characterisation of Staphylococcus aureus and Enterococcus faecalis mutants with reduced susceptibility to the investigational oxazolidinone RWJ-416457.
MedLine Citation:
PMID:  20846828     Owner:  NLM     Status:  MEDLINE    
RWJ-416457 is a novel investigational oxazolidinone with minimum inhibitory concentrations (MICs) to staphylococci and enterococci that are two- to four-fold lower than those of linezolid. Single-step and serial passage in vitro resistance selection experiments were performed for RWJ-416457 and linezolid with Staphylococcus aureus and Enterococcus faecalis laboratory and clinical isolates. RWJ-416457 selected for resistant mutants in single-step selections at a frequency of ≤1×10(-10), similar to that of linezolid. In serial passage selection experiments, a G2576T transversion in the domain V region of the 23S rRNA gene was the predominant mutation observed for both oxazolidinones, suggesting similar 23S rRNA binding sites. The associated development of increasing oxazolidinone resistance in E. faecalis (four 23S rRNA alleles) required fewer passages than with S. aureus isolates (six 23S rRNA alleles), and resistance was generally proportionate to the number of mutated (G2576T) 23S rRNA alleles. Fold changes in MICs were similar for both compounds, and MICs for RWJ-416457 remained two- to four-fold lower than those of linezolid for mutants selected by either compound. Serial passage of linezolid with S. aureus OC 2878 yielded a novel A2572T 23S rRNA mutation, whilst the final passages of S. aureus OC 10517 with RWJ-416457 resulted in the apparent loss of a mutated (G2576T) allele 6.
Colleen M Santoro; Karen Bush; Darren Abbanat
Related Documents :
8698658 - Quantification of staphylococcus aureus and escherichia coli in the liquid medium by fl...
12041758 - Immunoblot typing of oxacillin-resistant staphylococcus aureus clinical isolates.
4633678 - Present significance of resistance to trimethoprim and sulphonamides in coliforms, stap...
399288 - Diagnostic utilization of hemolytically active exosubstances of certain gram-positive b...
8662178 - Flexibacter japonensis sp. nov., a new species that produces a novel inhibitor of human...
24386558 - Probiotic therapy: a promising strategy for the control of canine hookworm.
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-09-17
Journal Detail:
Title:  International journal of antimicrobial agents     Volume:  36     ISSN:  1872-7913     ISO Abbreviation:  Int. J. Antimicrob. Agents     Publication Date:  2010 Nov 
Date Detail:
Created Date:  2010-10-11     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111860     Medline TA:  Int J Antimicrob Agents     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  424-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.
Johnson & Johnson Pharmaceutical Research and Development, LLC, Raritan, NJ 08869, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Anti-Bacterial Agents / pharmacology*
Blotting, Southern
Enterococcus faecalis / drug effects*,  genetics
Microbial Sensitivity Tests
Oxazolidinones / pharmacology*
Point Mutation*
RNA, Bacterial / genetics
RNA, Ribosomal, 23S / genetics
Sequence Analysis, DNA
Serial Passage
Staphylococcus aureus / drug effects*,  genetics
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Oxazolidinones; 0/RNA, Bacterial; 0/RNA, Ribosomal, 23S; 0/RWJ-416457

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

Previous Document:  CNS infection in childhood does not confer risk for later schizophrenia: a case-control study.
Next Document:  Longitudinal analysis of the in vitro activity profile of oritavancin and comparator glycopeptides a...