Predictors of 30-Day Mortality in Hospitalized Patients with Clostridium difficile Infection.

OBJECTIVES: Clostridium difficile infection (CDI) is a significant cause of morbidity and mortality and is the most common nosocomial infection in the United States, with associated annual costs of approximately $3 billion. The epidemiology of CDI has changed with the identification of novel risk factors for incident and recurrent CDI. The aim of this study was to identify the predictors of 30-day mortality in hospitalized patients with CDI. METHODS: We identified all of the patients diagnosed as having CDI from January 2011 to December 2014 at our university-setting hospital. Data were extracted using electronic medical records and chart review. The data of all of the patients who died within 30 days of incident CDI were compared with those who survived beyond 30 days of incident CDI. A multivariable logistic regression model was created for mortality after finding a subset of significant predictor variables by making bivariate comparisons also using logistic regression. RESULTS: A total of 893 patients were diagnosed as having CDI during the study period. The mean age was 62 years and 49.5% were women. The mean length of hospital stay was 11.73 days. Of the 893 patients with CDI, 98 (10.97%) died within 30 days of incident CDI. CDI recurrence was noted in 76 patients (8.51%). On multivariate logistic regression analysis, peptic ulcer disease, advanced age, Charlson comorbidity index, and intensive care unit status were found to be significantly associated with 30-day mortality. There was no significant association between acid suppression and CDI mortality. CONCLUSIONS: Advanced age, Charlson comorbidity index, intensive care unit status, and peptic ulcer disease are predictors of all-cause 30-day mortality in hospitalized patients with CDI.

Asc-dependent and independent mechanisms contribute to restriction of legionella pneumophila infection in murine macrophages.

The apoptosis-associated speck-like protein containing a caspase recruitment domain (Asc) is an adaptor molecule that mediates inflammatory and apoptotic signals. Legionella pneumophila is an intracellular bacterium and the causative agent of Legionnaire's pneumonia. L. pneumophila is able to cause pneumonia in immuno-compromised humans but not in most inbred mice. Murine macrophages that lack the ability to activate caspase-1, such as caspase(-1-/-) and Nlrc4(-/-) allow L. pneumophila infection. This permissiveness is attributed mainly to the lack of active caspase-1 and the absence of its down stream substrates such as caspase-7. However, the role of Asc in control of L. pneumophila infection in mice is unclear. Here we show that caspase-1 is moderately activated in Asc(-/-) macrophages and that this limited activation is required and sufficient to restrict L. pneumophila growth. Moreover, Asc-independent activation of caspase-1 requires bacterial flagellin and is mainly detected in cellular extracts but not in culture supernatants. We also demonstrate that the depletion of Asc from permissive macrophages enhances bacterial growth by promoting L. pneumophila-mediated activation of the NF-κB pathway and decreasing caspase-3 activation. Taken together, our data demonstrate that L. pneumophila infection in murine macrophages is controlled by several mechanisms: Asc-independent activation of caspase-1 and Asc-dependent regulation of NF-κB and caspase-3 activation.