Comparative potency of oxazolidinones tedizolid (TR-700) and linezolid against target gram-positive pathogens in the US from 2009-2010

Purpose: Resistance and multidrug resistance among Gram-positive pathogens, in particular Staphylococcus aureus, has limited the utility of many common antibacterials. Decreased susceptibility to daptomycin, linezolid, and vancomycin remains infrequent, but potential for growing resistance is a significant concern. Tedizolid (TR-700), formerly known as torezolid, is an oxazolidinone with potent activity against Gram-positive pathogens currently undergoing trials for the treatment of acute bacterial skin and skin structure infections (ABSSSI). This study reports the current susceptibility of target Gram-positive pathogens from the United States, comparing the activity profiles of TR-700 and linezolid. 

Methods: 1248 S aureus, 50 Enterococcus faecalis, 38 Enterococcus faecium, 101 Streptococcus pyogenes, 28 Streptococcus agalactiae, and 29 anginosus group streptococci (AGS) clinical isolates from 93 distributed sites from 2009 to 2010 were tested by broth microdilution per Clinical and Laboratory Standards Institute (CLSI) guidelines for susceptibility to TR-700, linezolid, and comparators. Resistance to ≥3 classes of agent (excluding beta-lactams) defined multidrug resistance among S aureus.

Results: TR-700 and linezolid (LZD) activity against evaluated isolates by phenotype was documented. Based on MIC₅₀/MIC₉₀, TR-700 was 4- to 8-fold more potent than linezolid. The activity profiles of TR-700 and linezolid were not impacted by resistance common among the evaluated pathogens (eg, MRSA, VRE, etc), and TR-700 maintained activity against linezolid-resistant isolates. Against the only linezolid-resistant S aureus and E faecium (TR-700 minimum inhibitory concentrations [MICs] of 16 and 32 mg/mL, respectively), TR-700 had MICs of 1 and 4 mg/mL, respectively. 

Conclusion: The activity profile of TR-700 highlights its potential for the treatment of Gram-positive infections such as ABSSSI, though emerging resistance warrants continued surveillance for all developmental and approved oxazolidinones.