In vitroActivity of Linezolid and Eperezolid, Two Novel Oxazolidinone Antimicrobial Agents, Against Anaerobic Bacteria

Abstract

Linezolid (formerly U-100766) and eperezolid (formerly U-100592) are novel oxazolidinone antimicrobial agents that are active against multi-drug-resistant staphylococci, streptococci, enterococci, corynebacteria, and mycobacteria. Preliminary studies also demonstrated that the compounds inhibited some test strains of anaerobic bacteria. Therefore, we extended thein vitroevaluation of these agents to include a total of 54 different anaerobic species. Minimal inhibitory concentration (MIC) values were determined using a standard agar dilution method for 143 anaerobic bacterial isolates. Eperezolid and linezolid demonstrated potent activity against the anaerobic Gram-positive organisms with most MIC values in the range of 0.25–4 μg/mL. Viridans streptococci demonstrated MICs of 1–2 μg/mL;Peptostreptococcusspecies andPropionibacteriumspecies were inhibited by ≤0.25–1 μg/mL. Clostridial species were generally susceptible to the oxazolidinones (MICs of ≤0.25–8 μg/mL); however, seven strains ofClostridium difficilewith linezolid MICs of 16 μg/mL or greater were detected. Against the anaerobic Gram-negative organisms, linezolid was more potent than eperezolid, especially forBacteroidesspecies. Linezolid inhibited most bacteroides in the range of 2–8 μg/mL, while eperezolid was generally two- to eight-fold less active. Linezolid and eperezolid both demonstrated potent activity againstFusobacteriumspecies,Mobiluncusspecies,Prevotella intermedia, andPorphyromonas asaccharolytica(MICs of ≤0.25–0.5 μg/mL). Overall, the oxazolidinones demonstrated a significant level of activity against a number of clinically-important anaerobic bacterial species. Linezolid may potentially provide a broader spectrum of anaerobic coverage than eperezolid due to its greater activity againstBacteroidesspecies.