In VitroandIn VivoAntibacterial Evaluation of Cadazolid, a New Antibiotic for Treatment of Clostridium difficile Infections
ABSTRACTClostridium difficileis a leading cause of health care-associated diarrhea with significant morbidity and mortality, and new options for the treatment ofC. difficile-associated diarrhea (CDAD) are needed. Cadazolid is a new oxazolidinone-type antibiotic that is currently in clinical development for treatment of CDAD. Here, we report thein vitroandin vivoantibacterial evaluation of cadazolid againstC. difficile. Cadazolid showed potentin vitroactivity againstC. difficilewith a MIC range of 0.125 to 0.5 μg/ml, including strains resistant to linezolid and fluoroquinolones. In time-kill kinetics experiments, cadazolid showed a bactericidal effect againstC. difficileisolates, with >99.9% killing in 24 h, and was more bactericidal than vancomycin. In contrast to metronidazole and vancomycin, cadazolid strongly inhibitedde novotoxin A and B formation in stationary-phase cultures of toxigenicC. difficile. Cadazolid also inhibitedC. difficilespore formation substantially at growth-inhibitory concentrations. In the hamster and mouse models for CDAD, cadazolid was active, conferring full protection from diarrhea and death with a potency similar to that of vancomycin. These findings support further investigations of cadazolid for the treatment of CDAD.