Reply to Walker et al

Studies of Clostridium difficile outbreaks suggested that certain ribotypes (eg, 027 and 078) cause more severe disease than other ribotypes. A growing number of studies challenge the validity of this hypothesis.We conducted a cross-sectional study of C. difficile infection (CDI) to test whether ribotype predicted clinical severity when adjusted for the influence of other predictors. Toxigenic C. difficile isolates were cultured from stool samples, screened for genes encoding virulence factors by polymerase chain reaction (PCR) and ribotyped using high-throughput, fluorescent PCR ribotyping. We collected data for 15 covariates (microbiologic, epidemiologic, and laboratory variables) and determined their individual and cumulative influence on the association between C. difficile ribotype and severe disease. We then validated this influence using an independent data set.A total of 34 severe CDI cases were identified among 310 independent cases of disease (11.0%). Eleven covariates, including C. difficile ribotype, were significant predictors of severe CDI in unadjusted analysis. However, the association between ribotypes 027 and 078 and severe CDI was not significant after adjustment for any of the other covariates. After full adjustment, severe cases were significantly predicted only by patients' white blood cell count and albumin level. This result was supported by analysis of a validation data set containing 433 independent CDI cases (45 severe cases; 10.4%).Ribotype is not a significant predictor of severe CDI when adjusted for the influence of any other variables separately or in combination. White blood cell count and albumin level are the most clinically relevant predictors of severe CDI cases.