Nocathiacin, Thiazomycin, and Polar Analogs Are Highly Effective Agents against Toxigenic .

is a commensal Gram-positive gut bacterium that causes -associated diarrhea. Currently available antibacterial therapeutic treatment options are effective except for the repeated recurrences significantly burdening the health care system and causing mortality. The development of new therapeutic modalities including new effective antibiotics with a low rate of recurrence has been unpredictive and exceedingly challenging, requiring continued profiling of many new classes of antibiotics. Nocathiacins and thiazomycins are a class of thiazolyl peptides exhibiting potent and selective broad-spectrum Gram-positive activity including activity against the anaerobe . These compounds showed MIC values of 0.015-0.06 μg/mL against with more than 100-200-fold selectivity versus commensurate Gram-negative . Nocathiacin I and one of its analogs exhibited potent efficacy in the gold-standard hamster model of infection, providing 100% protection in this lethal model at 6.25 mg/kg orally twice daily. The efficacy was corroborated by robust reduction of cecum burden and proportionate exposure of the compounds in the cecum contents without any systemic absorption. In this paper, details of the results of , , pharmacodynamics, and pharmacokinetic studies have been described.