We compared antibiotic consumption between hospitals affected by a strain of Clostridium difficile designated as polymerase chain reaction-ribotype 027 (CD-027) and those unaffected during an outbreak in northern France. The mean consumption of several beta-lactams, amikacin, and fluoroquinolones was high in affected hospitals (P < .05). However, only levofloxacin and imipenem remained associated with emerging CD-027 in the multivariate analysis, suggesting that those antibiotics should be better targeted by prevention campaigns.