In the second analysis, we only used patients with diarrhea. The time of CDI test performance was considered as Day method 0, and CDI infection was considered as a time-fixed covariate. Other covariates were introduced in a Cause Specific Hazard model as previously described.Results were presented with Cause Specific Hazard ratios (CSHRs) and 95% confidence intervals (95% CI). Models were stratified by center.Finally, we estimated the prolongation of ICU stay using the disability model approach [19]. We used a multi-state model with four states, and all diarrheic populations started in an initial state. Then, prolongation of ICU stay was determined by reaching one of two competing absorbing states, (death or discharge alive), by taking into account the intermediate state (ICU-acquired CDI).

Finally, we computed standard error estimation for prolongation of ICU stay thanks to the bootstrap method and 2,000 random samples with replacement and computed P-value using the Wald test. P-values < 0.05 were considered significant. Statistical analysis was performed using SAS 9.1 (SAS Institute, Cary, NC, USA). Length of stay prolongation was calculated with R software (R foundation, Vienna, Austria), using the change LOS library.Assuming a 40% rate of hospital death in the diarrheic population, 471 patients were necessary to detect a hazard ratio (HR) of 2 for death with greater than 90% power and a type I error of 0.05 [20]. Similarly, 4,290 patients were necessary, assuming a 35% rate of hospital death in the whole population.

Ethical issuesAccording to French law, this study did not require patient consent, as it involved research on a database. The study was approved by the institutional review board of the Centre d’Investigation Rh?ne-Alpes-Auvergne.ResultsFrom 5,260 patients collected in the three centers, 512 patients (9.7%) underwent CD toxin testing by enzyme-linked immunosorbent assay on fecal samples for an episode of watery or unformed stools, of which 69 (69/512 = 13.5%) patients were positive. This corresponds to an incidence of ICU-acquired diarrhea of 0.97/1,000 patients-days (Figure (Figure11).Figure 1Flow chart of patients.Among the 512 patients tested, 315 (61.5%) were men, median age was 67 years (1st and 3rd Quartiles: 56 to 76 years) and the average SAPS and LOD were respectively 45 (1st and 3rd Quartiles: 36 to 59) and 6 (1st and 3rd Quartiles: 4 to 8).

At least one chronic illness was present in 226 (44.1%) patients, and 128 (25%) patients died during ICU stay (33.8% during hospital stay). Characteristics of tested, ICU-acquired CDI patients, and non ICU-acquired CDI patients are shown in Table Table11.Table 1Patients’ characteristics.The case group consisted of 47 (68%) ICU-acquired GSK-3 CDI (incidence: 3.6/1,000 patient-days). Of these patients with CDI, 24 (51%) had a pseudomembranous colitis (incidence 1.