Multi-institution case–control and cohort study of risk factors for the development and mortality of Clostridium difficile infections in Japan

OBJECTIVE To examine risk factors for Clostridium difficile infection (CDI) morbidity and mortality in Japan. DESIGN Multimethod investigation including a case-control study and cohort study. SETTING 47 participating facilities of the National Hospital Organization (NHO). PARTICIPANTS 1026 patients with CDI and 878 patients in the control group over the age of 18 years admitted to the subject NHO facilities from November 2010 to October 2011. MAIN OUTCOME MEASURES In a case-control study, we identify risk factors for CDI development. Next, in a cohort study, we identify risk factors for all-cause mortality within 30 days following CDI onset. RESULTS A total of 1026 cases of CDI meeting the definitions of this investigation were identified, encompassing 878 patients at 42 of the 47 subject facilities. In the case-control study, we identified, compared with no antibiotics use, use of first-generation and second-generation cephem antibiotics (OR 1.44; 95% CI 1.10 to 1.87), use of third-generation and fourth-generation cephem antibiotics (OR 1.86; 95% CI 1.48 to 2.33) and use of carbapenem antibiotics (OR 1.87; 95% CI 1.44 to 2.42) the risk factors for CDI development. However, use of penicillin was not identified as a risk factor. In the cohort study, sufficient data for analysis was available for 924 CDI cases; 102 of them (11.0%) resulted in death within 30 days of CDI onset. Compared with no anti-CDI drug use, use of vancomycin was associated with reduced risk of mortality (OR 0.43; 95% CI 0.25 to 0.75) whereas metronidazole was not. CONCLUSIONS The findings mirror those of previous studies from Europe and North America, identifying the administration of broad-spectrum antibiotics as a risk factor for CDI development. The use of vancomycin is associated with a decreased risk of mortality.