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

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 μg/ml, MIC 90 ≤ 0.5 μg/ml), coagulase-negative staphylococci (CNS; MIC 50 = 0.25 μg/ml, MIC 90 ≤ 0.5 μg/ml), enterococci (MIC 50 and MIC 90 ≤ 0.5 μg/ml), and streptococci (MIC 50 and MIC 90 ≤ 0.25 μg/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 ≤2 μg/ml for susceptibility, torezolid disk diffusion zone diameter breakpoints are proposed using a 20-μg disk. In addition, MIC quality control ranges of torezolid were determined for three CLSI-recognized standard ATCC reference strains.