Comparative in vitro antimicrobial activities of torezolid (TR-700), the active moiety of a new oxazolidinone, torezolid phosphate (TR-701), determination of tentative disk diffusion interpretive criteria, and quality control ranges

Abstract

This study assessed the spectrum of activity of torezolid (TR-700), the active moiety of torezolid phosphate (TR-701), and proposes tentative MIC and disk diffusion breakpoints as well as quality control ranges. The in vitro susceptibilities of 1,096 bacterial isolates, representing 23 different species or phenotypic groups, were determined for torezolid, linezolid, cefotaxime, and levofloxacin using Clinical and Laboratory Standards Institute (CLSI) broth microdilution MICs, minimum bactericidal concentrations (MBCs), agar dilution, and disk diffusion testing methods. Torezolid was very active against the majority of Gram-positive strains, including methicillin-susceptible and -resistant Staphylococcus aureus (MIC(50) = 0.25 microg/ml, MIC(90) <or= 0.5 microg/ml), coagulase-negative staphylococci (CNS; MIC(50) = 0.25 microg/ml, MIC(90) <or= 0.5 microg/ml), enterococci (MIC(50) and MIC(90) <or= 0.5 microg/ml), and streptococci (MIC(50) and MIC(90) <or= 0.25 microg/ml). Based upon MIC(90)s, torezolid was 4-fold more active than linezolid against S. aureus, coagulase-negative staphylococci, and the enterococci and 8-fold more active than linezolid against the streptococci. With the use of tentative MIC breakpoints of <or=2 microg/ml for susceptibility, torezolid disk diffusion zone diameter breakpoints are proposed using a 20-microg disk. In addition, MIC quality control ranges of torezolid were determined for three CLSI-recognized standard ATCC reference strains.

FIG. 1.

Scattergrams of torezolid versus zone diameters (20-μg disks). (A) All staphylococci combined using transmitted light (n = 338). (B) All staphylococci combined using reflected light (n = 338). (C) Enterococcal species combined (n = 202). (D) All streptococci combined (n = 361). Horizontal lines represent proposed susceptible (lower line), susceptible-only, and resistant (upper line) MIC breakpoints; vertical lines represent proposed susceptible (right line), susceptible-only, and resistant (left line) zone diameter breakpoints. Abbreviations: n, number of strains tested; VM, very major errors; M, major errors; m, minor errors; n.a., not applicable; R, resistant; S, susceptible.

FIG. 2.

Bar graph (left) and scattergram (right) showing torezolid broth microdilution MICs versus torezolid agar dilution MICs for S. aureus (n = 104), Enterococcus spp. (n = 105), and S. pneumoniae (n = 106). Vertical bars represent ±1 doubling dilution from complete agreement.