Although
vancomycin and
metronidazole effectively treat Clostridium difficile-associated
diarrhea and
colitis (CDAD), their use is associated with a high incidence of relapsing C. difficile
infection.
Rifalazil is a new
benzoxazinorifamycin that possesses activity against Mycobacterium tuberculosis and gram-positive bacteria. Here we compared
rifalazil and
vancomycin for effectiveness in preventing or treating
clindamycin-induced
cecitis in a hamster model of CDAD. Golden Syrian hamsters were injected subcutaneously with
clindamycin phosphate (10 mg/kg), followed 24 h later by C. difficile gavage. Hamsters received by gavage for 5 days vehicle,
vancomycin (50 mg/kg), or
rifalazil (20 mg/kg) either simultaneously with (prophylactic protocol) or 24 h after C. difficile administration (treatment protocol). While all vehicle-administered animals became moribund within 48 h of C. difficile administration, no
rifalazil- or
vancomycin-treated animals in either protocol showed signs of morbidity after 7 days. Ceca of
rifalazil-treated animals showed absence of epithelial cell damage, significantly reduced congestion and
edema, and less, but not statistically significantly less, neutrophil infiltration compared to those of vehicle-treated animals. In contrast,
vancomycin-treated animals demonstrated severe epithelial cell damage and mildly reduced congestion and
edema. Moreover, hamsters relapsed and tested C. difficile toxin positive (by
enzyme-linked
immunosorbent assay) 10 to 15 days after discontinuation of
vancomycin treatment. None of the
rifalazil-treated hamsters showed signs of disease or presence of toxins in their feces 30 days after discontinuation of treatment. Our results indicate that once daily
rifalazil may be superior to
vancomycin for curative treatment of CDAD.