title: In vitro activity 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 the in vitro evaluation 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 microg/mL. Viridans streptococci demonstrated MICs of 1-2 microg/mL; Peptostreptococcus species and Propionibacterium species were inhibited by </=0.25-1 microg/mL. Clostridial species were generally susceptible to the oxazolidinones (MICs of </=0.25-8 microg/mL); however, seven strains of Clostridium difficile with linezolid MICs of 16 microg/mL or greater were detected. Against the anaerobic Gram-negative organisms, linezolid was more potent than eperezolid, especially for Bacteroides species. Linezolid inhibited most bacteroides in the range of 2-8 microg/mL, while eperezolid was generally two- to eight-fold less active. Linezolid and eperezolid both demonstrated potent activity against Fusobacterium species,Mobiluncus species,Prevotella intermedia, and Porphyromonas asaccharolytica (MICs of </=0.25-0.5 microg/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 against Bacteroides species.
authors.affiliation: Pharmacia & Upjohn, Inc. Infectious Diseases Research, Kalamazoo, MI 49001, USA.
authors.forename: B H
authors.initials: BH
authors.lastname: Yagi
authors.forename: G E
authors.initials: GE
authors.lastname: Zurenko