To better understand the epidemiology of CDAD infection in critically ill patients, we investigated its clinical course and outcome in the intensive care units of a tertiary care, academic medical center. Of the 58 ICU patients with C. difficile colitis in our cohort study, a significant proportion of these patients had concurrent infection (62.1%). The majority of the pathogens associated with nosocomial infections in our study cohort were gastrointestinal flora. This finding coupled with the relatively high proportion of bloodstream infections that were polymicrobial suggest that the inflammation and disruption of the colonic mucosa by CDAD provided a source of entry for organisms into the bloodstream. Of note, 60% of these patients had recently been treated with antimicrobials with significant activity against anaerobes, suggesting an important protective role that anaerobes may play in the intestinal flora. Similarly, disruption of the anaerobic gut flora has been shown to be a risk factor for VRE colonization , an epidemiologic finding that has been experimentally validated in an animal model .
As more than a half of our C. difficile patients were co-infected, findings predictably showed that a high proportion of ICU CDAD patients had a maximal SIR (severe sepsis, septic shock or death) during 14 days of follow-up. However, no statistically difference was observed in maximal SIR between patients with CDAD only those with CDAD and another infection (p = 0.17). One potential explanation for this observation may have been the delay in the introduction of specific antimicrobial therapy (metronidazole or oral vancomycin) for patients with CDAD. In our study, ICU patients were symptomatic with diarrhea on average for 6.5 days prior to microbiologic confirmation of the CDAD diagnosis and initiation of therapy. In our study cohort, no patients required surgical procedures as a result of CDAD. This is similar to another report in which 2.5% of patients required emergency colectomy .
Some studies have shown that treatment of CDAD with metronidazole may lead to poor outcomes [21, 22]. In our study it was not our purpose to determine the efficacy of metronidazole since we had multiple confounders such as a high rate of co-infection, and some patients died before completing metronidazole treatment. Almost one-fifth of our patients received antibiotics in the absence of evidence to suggest a concurrent infection. This observation is particularly important as prior reports suggest that unnecessary antibiotic use makes treatment of CDAD more difficult and potentially less efficacious [2, 3].
The crude mortality rate associated with C. difficile diarrhea in our ICU population was high (27.6%). Similarly, a prospective study at 12 Quebec hospitals of 1,073 patients with CDAD found a 30-day crude mortality rate of 24.8% independent of being ICU or non-ICU patients . In this study, Loo et al. found that the age-specific incidence of CDAD increased markedly after the age of 50 years and the attributable mortality rate increased after the age of 60 years . Pepin et al. have also found that advanced age (≥65 years) is a risk factor for recurrence of CDAD following treatment with metronidazole. By multivariate analysis, we demonstrated that for ICU patients with CDAD, advanced age and a high SOFA score were independent predictors of mortality. Prior studies have identified advanced age as a risk factor for CDAD [11, 24]. To our knowledge, no other studies have reported SOFA score as a predictor for mortality in ICU patients with CDAD.
The limitations of our study should be acknowledged. First, we performed a retrospective cohort study; second, we only evaluated patients during hospitalization. Thus, we cannot comment on long term follow-up, including relapse of diarrhea and mortality. Third, these findings were specific for an ICU population in a tertiary care medical center and thus may not be generalizable to a non-ICU population. Fourth, as this study lacked controls, we did not investigate risk factors for the development of CDAD in our ICU population. Lastly, the study had a small sample size thereby potentially resulting in a type II error at the time of univariate and multivariate analysis.