Anti-anaerobic potential of ranbezolid: insight into its mechanism of action against Bacteroides fragilis

This study reports the anti-anaerobic properties of ranbezolid, a new investigational oxazolidinone. A time-kill kinetics study against anaerobes showed that ranbezolid was superior to linezolid and killed the anaerobic pathogens at 4-8 h, except for Bacteroides fragilis where killing was observed at 24 h. In addition, the time-kill kinetics study showed a concentration-dependent bactericidal potential of ranbezolid against anaerobes. Ranbezolid showed 5.39 log(10) reduction and linezolid showed 1.15 log(10) reduction in murine disk implant infection with B. fragilis ATCC 25285. Ranbezolid was very potent and showed fast protein synthesis inhibition against B. fragilis, a Gram-negative anaerobe. In addition, non-specific cell wall synthesis inhibition was also observed with ranbezolid. The potent and fast protein synthesis inhibition along with an additional mode of action of cell wall synthesis inhibition could be responsible for the cidal effect of ranbezolid against Gram-negative anaerobes. (C) 2012 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.