A Potent and Narrow-Spectrum Antibacterial against Clostridioides difficile Infection.

is an anaerobic Gram-positive bacterium that colonizes the gut of patients treated with broad-spectrum antibiotics. The normal gut microflora prevents . colonization; however, dysbiosis by treatment with broad-spectrum antibiotics causes recurrent . infection (CDI) in 25% of patients. There are no fully effective antibiotics for multiple recurrent CDIs. We report herein that oxadiazole antibiotics exhibit bactericidal activity against . vegetative cells. We screened a library of 75 oxadiazoles against . ATCC 43255. The findings from this collection served as the basis for the syntheses of an additional 58 analogs, which were tested against the same strain. We report a potent (MIC = 0.5 μg/mL and MIC = 1 μg/mL values for 101 . strains) and narrow-spectrum oxadiazole (3-(4-(cyclopentyloxy)phenyl)-5-(4-nitro-1-imidazol-2-yl)-1,2,4-oxadiazole; compound ), which is not active against common gut bacteria or other tested organisms. Compound is selectively bactericidal against . and targets cell-wall synthesis.