LCB01-0371 is a new oxazolidinone with cyclic amidrazone. In vitro activity of LCB01-0371 against 624 clinical isolates was evaluated and compared with those of linezolid, vancomycin, and other antibiotics. LCB01-0371 showed good activity against Gram-positive pathogens. In vivo activity of LCB01-0371 against systemic infections in mice was also evaluated. LCB01-0371 was more active than linezolid against these systemic infections. LCB01-0371 showed bacteriostatic activity against Staphylococcus aureus.The emergence of multidrug-resistant (MDR) pathogens, such as methicillin-resistant Staphylococcus aureus (MRSA), methicillin-resistant coagulase-negative staphylococci (MRCNS), penicillin-resistant Streptococcus pneumoniae (PRSP), and vancomycinresistant enterococci (VRE), has generated worldwide concern in the medical community (11). The requirement for effective new antimicrobial agents to treat infections caused by Gram-positive organisms is becoming urgent as resistance to existing agents arises and spreads around the world.The oxazolidinones, a totally synthetic class of novel antibiotics, have strong activity against nearly all Gram-positive organisms, including those resistant to other agents (1, 10). They inhibit protein synthesis by binding to domain V of the 23S rRNA and thereby blocking formation of the initiation complex (6). Linezolid is the first member of the oxazolidinone class approved by the FDA in the United States. The success of linezolid and the occurrence of strains resistant to linezolid in clinical isolates of Enterococcus faecium (4, 5) and S. aureus (12) have inspired further efforts toward developing new oxazolidinones with improved safety and antibacterial activity.LCB01-0371 ( Fig. 1), a novel oxazolidinone with cyclic amidrazone, was synthesized by LegoChem BioSciences Inc. (Daejeon, Republic of Korea). In this study, in vitro activity of LCB01-0371 was compared with those of eight different antibacterial agents against 624 clinical isolates that were collected from several general hospitals in the Republic of Korea. In vivo activity of LCB01-0371 against systemic infections in mice and time-kill studies of LCB01-0371 against S. aureus giorgio (methicillin-susceptible S. aureus [MSSA]) and S. aureus p125 (MRSA) were also investigated.(This study was presented in part at the 49th Annual Interscience Conference on Antimicrobial Agents and Chemotherapy, San Francisco, CA, 2009 [7].)In vitro MICs were determined by the 2-fold agar dilution method as described by the Clinical and Laboratory Standards Institute (CLSI) (3). Mueller-Hinton agar (MHA) medium was used for testing aerobic and facultative organisms. Streptococcus pneumoniae, Streptococcus pyogenes, and Moraxella catarrhalis were grown on Mueller-Hinton agar supplemented with 5% defibrinated sheep blood (Hanil Komed Ltd., Sungnam City, Republic of Korea). Mueller-Hinton agar supplemented with 3% Fildes enrichment (Oxoid Ltd., Basingstoke, Hampshire, England) was used for Haemophilus influenzae. Bacteria (10 4 to 10 5 CFU) were s...

Oxazolidinones are a novel class of synthetic antibacterial agents that inhibit bacterial protein synthesis. Here, we synthesized and tested a series of oxazolidinone compounds containing cyclic amidrazone. Among these compounds, we further investigated the antibacterial activities of LCB01-0648 against drug-susceptible or resistant Gram-positive cocci in comparison with those of six reference compounds. LCB01-0648 showed the most potent antimicrobial activities against clinically isolated Gram-positive bacteria. Against the methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant coagulase-negative staphylococci (MRCNS) isolates, LCB01-0648 showed the lowest MIC90s (0.5 mg/L) among the tested compounds. In addition, LCB01-0648 had the lowest minimum inhibitory concentrations (MICs) against the four linezolid-resistant S. aureus (LRSA) strains (range 2–4 mg/L). The results of the time–kill studies demonstrated that LCB01-0648 at a concentration 8× the (MIC) showed bactericidal activity against methicillin-susceptible Staphylococcus aureus MSSA or MRSA, but showed a bacteriostatic effect against LRSA. These results indicate that LCB01-0648 could be a good antibacterial candidate against multidrug-resistant (MDR) Gram-positive cocci.