Antibody-based binding agents derived from human and camelid immunoglobulins are described, as well as strains of yeast engineered to secrete the binding agents, and methods of treating and preventing Clostridium difficile infections using the engineered strains of yeast. These binding agents recognize and bind with specificity to Clostridium difficile toxin A and/or toxin B and in some cases exhibit toxin neutralizing activity. The binding agents include camelid VHH peptide monomers, linked groups of VHH peptide monomers, VHH peptide monomers joined to antibody Fc domains, and VHH peptide monomers joined to IgG antibodies.