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. 2008 Dec;52(12):4442-7.
doi: 10.1128/AAC.00859-08. Epub 2008 Oct 6.

In vitro activity of TR-700, the antibacterial moiety of the prodrug TR-701, against linezolid-resistant strains

K J Shaw  1 , S Poppe, R Schaadt, V Brown-Driver, J Finn, C M Pillar, D Shinabarger, G Zurenko
Affiliations

In vitro activity of TR-700, the antibacterial moiety of the prodrug TR-701, against linezolid-resistant strains

K J Shaw et al. Antimicrob Agents Chemother. 2008 Dec.

Abstract

TR-701 is the orally active prodrug of TR-700, a novel oxazolidinone that demonstrates four- to eightfold-greater activity than linezolid (LZD) against Staphylococcus and Enterococcus spp. In this study evaluating the in vitro sensitivity of LZD-resistant isolates, TR-700 demonstrated 8- to 16-fold-greater potency than LZD against all strains tested, including methicillin-resistant Staphylococcus aureus (MRSA), strains of MRSA carrying the mobile cfr methyltransferase gene, and vancomycin-resistant enterococci. The MIC(90) for TR-700 against LZD-resistant S. aureus was 2 microg/ml, demonstrating the utility of TR-700 against LZD-resistant strains. A model of TR-700 binding to 23S rRNA suggests that the increased potency of TR-700 is due to additional target site interactions and that TR-700 binding is less reliant on target residues associated with resistance to LZD.

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Figures

FIG. 1.
FIG. 1.
Model of TR-700 versus LZD in the peptidyl transferase binding site (PTS). (A) LZD (yellow) in the PTS (18). (B) Structure of LZD and TR-700. (C) TR-700 (cyan) in the PTS. Critical hydrogen bond interactions are shown in purple. The E. coli 23S numbering system is used.
See this image and copyright information in PMC

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