DOI: 10.1128/AAC.00723-10
Article Figures & Data
Figures
- FIG. 1.
Chemical structure of LCB01-0371.
- FIG. 2.
Time-kill curves of LCB01-0371 and linezolid against S. aureus giorgio (MSSA) and S. aureus p125 (MRSA).
Tables
- TABLE 1.
In vitro antibacterial activities of LCB01-0371 against clinical isolates
Microorganism (no. of strains) and compound MIC (μg/ml) Range 50% 90% MSSA (69) LCB01-0371 ∼0.5-2 1 2 Linezolid ∼2-4 2 2 Oxacillin ∼0.06-1 0.25 0.5 Erythromycin ∼0.125->64 0.25 >64 Ciprofloxacin ∼0.06->64 0.25 0.5 Moxifloxacin ∼0.015-64 0.06 0.125 Gemifloxacin ∼0.008-64 0.015 0.06 Vancomycin ∼0.25-2 1 1 Quinupristin-dalfopristin ∼0.125-0.5 0.25 0.5 ∼0.125->64 >64 >64 MRSA (202) LCB01-0371 ∼0.5-4 1 2 Linezolid ∼2-2 2 2 Oxacillin ∼2->64 >64 >64 Erythromycin ∼0.25->64 >64 >64 Ciprofloxacin ∼0.125->64 32 >64 Moxifloxacin ∼0.03->64 4 64 Gemifloxacin ∼0.008->64 2 64 Vancomycin ∼0.5-4 1 2 Quinupristin-dalfopristin ∼0.125-1 0.5 1 ∼0.125->64 >64 >64 MSCNS (20) LCB01-0371 ∼0.5-1 0.5 0.5 Linezolid ∼1-2 1 2 Oxacillin ∼0.03-1 0.125 1 Erythromycin ∼0.06->64 0.25 >64 Ciprofloxacin ∼0.06-8 0.125 8 Moxifloxacin ∼0.03-4 0.125 4 Gemifloxacin ∼0.008-0.5 0.015 0.5 Vancomycin ∼1-4 2 4 Quinupristin-dalfopristin ∼0.125-1 0.25 1 ∼>64->64 >64 >64 MRCNS (33) LCB01-0371 ∼0.5-1 0.5 0.5 Linezolid ∼1-2 1 1 Oxacillin ∼2->64 >64 >64 Erythromycin ∼0.06->64 >64 >64 Ciprofloxacin ∼0.06-64 8 32 Moxifloxacin ∼0.06-16 2 8 Gemifloxacin ∼0.008-8 0.5 1 Vancomycin ∼1-4 2 2 Quinupristin-dalfopristin ∼0.125-8 0.25 1 S. pneumoniae (97) LCB01-0371 ∼0.125-2 0.5 1 Linezolid ∼0.5-1 1 1 Oxacillin ∼0.008->64 8 16 Erythromycin ∼0.008->64 64 >64 Ciprofloxacin ∼0.5-32 1 2 Moxifloxacin ∼0.06-4 0.25 0.5 Gemifloxacin ∼0.008-0.25 0.03 0.06 Vancomycin ∼0.25-1 0.5 1 Quinupristin-dalfopristin ∼0.5-4 1 2 S. pyogenes (46) LCB01-0371 ∼0.5-2 1 2 Linezolid ∼1-2 2 2 Oxacillin ∼0.03-16 0.5 8 Erythromycin ∼0.008-8 0.06 2 Ciprofloxacin ∼0.5-2 1 2 Moxifloxacin ∼0.125-0.25 0.125 0.25 Gemifloxacin ∼0.015-0.125 0.03 0.06 Vancomycin ∼0.5-1 1 1 Quinupristin-dalfopristin ∼0.25-4 1 2 E. faecalis (109) LCB01-0371 ∼1-2 2 2 Linezolid ∼1-2 2 2 Oxacillin ∼8->64 16 >64 Erythromycin ∼0.125->64 >64 >64 Ciprofloxacin ∼0.06->64 2 64 Moxifloxacin ∼0.06-64 1 32 Gemifloxacin ∼0.008-16 0.125 4 Vancomycin ∼0.5-64 2 4 Quinupristin-dalfopristin ∼0.25-16 4 16 E. faecium (29) LCB01-0371 ∼1-2 2 2 Linezolid ∼1-2 2 2 Oxacillin ∼16->64 >64 >64 Erythromycin ∼0.125->64 >64 >64 Ciprofloxacin ∼1-64 4 64 Moxifloxacin ∼0.25->64 4 32 Gemifloxacin ∼0.03-64 2 16 Vancomycin ∼0.5-8 1 2 Quinupristin-dalfopristin ∼0.25-32 0.5 4 VRE (16) LCB01-0371 ∼1-1 1 1 Linezolid ∼2-2 2 2 Oxacillin ∼32->64 >64 >64 Erythromycin ∼>64->64 >64 >64 Ciprofloxacin ∼0.5-4 4 4 Moxifloxacin ∼0.25-4 2 4 Gemifloxacin ∼0.015-2 0.5 2 Vancomycin ∼>64->64 >64 >64 Quinupristin-dalfopristin ∼0.5-2 2 2 M. catarrhalis (20) LCB01-0371 ∼2-8 4 8 Linezolid ∼4-8 8 8 Oxacillin ∼0.25-32 8 16 Ciprofloxacin ∼<0.008-0.06 0.03 0.06 Moxifloxacin ∼0.015-0.06 0.06 0.06 Gemifloxacin ∼<0.008-0.03 <0.008 0.015 Vancomycin ∼64->64 64 >64 Quinupristin-dalfopristin ∼0.5-2 1 1 H. influenzae (13) LCB01-0371 ∼2-16 8 16 Linezolid ∼8-32 16 32 Oxacillin ∼>32->32 >32 >32 Erythromycin ∼0.5-8 2 8 Ciprofloxacin ∼<0.008-<0.008 <0.008 <0.008 Moxifloxacin ∼0.008-0.015 0.008 0.008 Gemifloxacin ∼<0.008-<0.008 <0.008 <0.008 Vancomycin ∼>64->64 >64 >64 Quinupristin-dalfopristin ∼2-8 4 8 - TABLE 2.
In vivo activities of LCB01-0371 against systemic infection in mice
Microorganism (inoculum, CFU/mousea) Antimicrobial agentb MIC (μg/ml) ED50, mg/kg (95% confidence limit) S. aureus giorgio, MSSA LCB01-0371 1 4.53 (∼2.26-7.87) (1 × 107) Linezolid 2 8.05 (∼4.70-13.85) S. aureus p125, MRSA LCB01-0371 1 2.96 (∼0.00-5.81) (1 × 108) Linezolid 2 4.84 (∼0.01-12.66) E. faecalis u810 LCB01-0371 2 4.53 (∼2.26-7.87) (2 × 108) Linezolid 2 5.97 (∼2.23-7.87) S. pneumoniae ATCC 6305 LCB01-0371 0.5 2.28 (∼0.00-4.49) (1 × 104) Linezolid 1 9.10 (∼4.92-23.72) H. influenzae hd2 LCB01-0371 8 9.96 (∼4.26-16.75) (7.5 × 108) Linezolid 16 21.43 (∼9.99-450.60)
