Increasing evidence suggests that altered intestinal microbial composition and function result in an increased risk of Clostridium difficile-associated diarrhoea (CDAD); however, the specific changes of intestinal microbiota in children suffering from CDAD and their associations with C. difficile strain toxigenicity are poorly understood. High-throughput pyrosequencing showed that reduced faecal bacterial diversity and dramatic shifts of microbial composition were found in children with CDAD. The Firmicutes/Bacteroidetes ratio was increased significantly in patients with CDAD, which indicated that dysbiosis of faecal microbiota was closely associated with CDAD. C. difficile infection resulted in an increase in lactate-producing phylotypes, with a corresponding decrease in butyrate-producing bacteria. The decrease in butyrate and lactate buildup impaired intestinal colonisation resistance, which increased the susceptibility to C. difficile colonisation. Strains of C. difficile which were positive for both toxin A and toxin B reduced faecal bacterial diversity to a greater degree than strains that were only toxin B-positive, and were associated with unusually abundant Enterococcus, which implies that the C. difficile toxins have different impacts on the faecal microbiota of children. Greater understanding of the relationships between disruption of the normal faecal microbiota and colonisation with C. difficile that produces different toxins might lead to improved treatment.

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Importance Clostridium difficile‐associated diarrhea (CDAD) is a severe type of antibiotic‐associated diarrhea (AAD). However, the risk factors for CDAD in children with AAD have not yet been clarified. Objective To investigate the distribution and risk factors for CDAD among hospitalized children in Beijing Children’s Hospital. Methods Stool samples from 197 children with AAD were tested for the C. difficile pathogenic genes (tcdA, tcdB, tcdC, tcdD, tcdE, cdtA, and cdtB) using polymerase chain reaction between January 2011 and January 2014. Children who tested positive for tcdA or tcdB were included in the CDAD group, and those remaining comprised the non‐CDAD group. Results The rate of CDAD among the 197 children with AAD was 42.6% (84/197). The age distribution was 1–15.6 years, among which the majority of children (54.8%, 46/84) were aged 1–4 years. Differences in the CDAD‐positive rates among AAD children belonging to different age groups were not statistically significant. Univariate analysis revealed that the duration of antibiotic therapy, the length of hospitalization prior to diarrhea, and gastrointestinal tract operations were significant risk factors (P < 0.05). Children with CDAD underwent more antibiotic therapy and had longer periods of hospitalization prior to diarrhea onset than children in the non‐CDAD group. Using multivariate regression analysis, hospitalization for ≥ 10 days prior to diarrhea was found to be an independent risk factor for CDAD. Interpretation This study revealed that the length of hospitalization (≥ 10 days) prior to diarrhea was an independent risk factor for CDAD in children with AAD.