Polypeptide products, methods, pharmaceutical compositions, and kits are provided for treating a subject exposed to, or at risk for exposure to, C. difficile microbial pathogens and toxin B produced by C. difficile (TcdB) pathogens. The methods, compositions and kits include a single domain, anti-TedB VHH polypeptide (antibody), or toxin B binding portion thereof, that specifically binds to and/or neutralizes TedB and treats or prevents illness and disease associated with C. difficile infection and TedB intoxication. The anti-TcdB VHHs, or toxin B binding portion thereof, may be recombinantly produced.