Clostridium difficile causes infections of the colon in susceptible patients. 
Specifically, gut dysbiosis induced by treatment with broad-spectrum antibiotics 
facilitates germination of ingested C. difficile spores, expansion of vegetative 
cells, and production of symptom-causing toxins TcdA and TcdB. The current 
standard of care for C. difficile infections (CDI) consists of administration of 
antibiotics such as vancomycin that target the bacterium but also perpetuate gut 
dysbiosis, often leading to disease recurrence. The monoclonal antitoxin 
antibodies actoxumab (anti-TcdA) and bezlotoxumab (anti-TcdB) are currently in 
development for the prevention of recurrent CDI. In this study, the effects of 
vancomycin or actoxumab/bezlotoxumab treatment on progression and resolution of 
CDI were assessed in mice and hamsters. Rodent models of CDI are characterized 
by an early severe phase of symptomatic disease, associated with high rates of 
morbidity and mortality; high intestinal C. difficile burden; and a disrupted 
intestinal microbiota. This is followed in surviving animals by gradual recovery 
of the gut microbiota, associated with clearance of C. difficile and resolution 
of disease symptoms over time. Treatment with vancomycin prevents disease 
initially by inhibiting outgrowth of C. difficile but also delays microbiota 
recovery, leading to disease relapse following discontinuation of therapy. In 
contrast, actoxumab/bezlotoxumab treatment does not impact the C. difficile 
burden but rather prevents the appearance of toxin-dependent symptoms during the 
early severe phase of disease, effectively preventing disease until the 
microbiota (the body's natural defense against C. difficile) has fully 
recovered. These data provide insight into the mechanism of recurrence following 
vancomycin administration and into the mechanism of recurrence prevention 
observed clinically with actoxumab/bezlotoxumab.