Clostridium difficile infection (CDI) is a
public health threat that results in 14,000 annual deaths in the United States. Challenges involve the production of CDI spores that can remain dormant for years and the production of toxins that damage the gut. Current therapies for CDI include
vancomycin and
metronidazole, but neither inhibits
spore or
toxin production. Thus, recurrence of infection occurs in 25% of patients and there are no
antibiotics that are effective for multiple recurrences. We describe oxadiazoles with activity against C. difficile, including the highly virulent
NAP1 / 027 strain with increased production of toxins A and B, as well as the additional binary
toxin.
Oxadiazole 2 is poorly absorbed, thus advantageously achieving high concentrations in the gut. The compound targets
peptidoglycan synthesis and inhibits vegetative cells, spores, and
toxin production.