Ceftobiprole and ceftobiprole medocaril did not promote growth of or toxin production by Clostridium difficile in mouse cecal contents, whereas ceftazidime, cefoxitin, ceftriaxone, cefotaxime, and ertapenem did. The relatively low propensity of ceftobiprole to promote C. difficile was attributable to inhibitory activity against C. difficile and sparing of anaerobic microflora.