High APACHE II score (aOR 1.112, 95% CI 1.014–1.219; p < 0.05), high C-reactive protein (aOR 1.011; 95% CI 1.004–1.019; p < 0.01) and carbapenem usage in past 90 days (aOR 3.259; 95% CI 1.105–9.609; p < 0.05) were independent risk factors of severe CDI. This evidence concerns the gene CRP and clostridium difficile infection.