Severity of C. difficile Infection in IBD
Severity of C. difficile Infection in IBD
Background The increasing incidence of Clostridium difficile (C. difficile) infection (CDI) among patients with inflammatory bowel disease is well recognised. However, most studies have focused on demonstrating that CDI is associated with adverse outcomes in IBD patients. Few have attempted to identify predictors of severe outcomes associated with CDI among IBD patients.
Aim To identify clinical and laboratory factors that predict severe outcomes associated with CDI in IBD patients.
Methods From a multi-institution EMR database, we identified all hospitalised patients with at least one diagnosis code for C. difficile from among those with a diagnosis of Crohn's disease or ulcerative colitis. Our primary outcome was time to total colectomy or death with follow-up censored at 180 days after CDI. Cox proportional hazards models were used to identify predictors of the primary outcome from among demographic, disease-related, laboratory and medication variables.
Results A total of 294 patients with CDI-IBD were included in our study. Of these, 58 patients (20%) met our primary outcome (45 deaths, 13 colectomy) at a median of 31 days. On multivariate analysis, serum albumin <3 g/dL (HR 5.75, 95% CI 1.34–24.56), haemoglobin below 9 g/dL (HR 5.29, 95% CI 1.58–17.69) and creatinine above 1.5 mg/dL (HR 1.98, 95% CI 1.04–3.79) were independent predictors of our primary outcome. Examining laboratory parameters as continuous variables or shortening our primary outcome to include events within 90 days yielded similar results.
Conclusion Serum albumin below 3 g/dL, haemoglobin below 9 g/dL and serum creatinine above 1.5 mg/dL were independent predictors of severe outcomes in hospitalised IBD patients with Clostridium difficile infection.
There has been a recent increase in the incidence and severity of Clostridium difficile infection (CDI). Such infections account for an estimated $750 million–$3.2 billion in healthcare costs. While CDI was traditionally linked to antibiotic use or healthcare contact, recent research has identified several new at-risk groups. One such group includes patients with underlying inflammatory bowel disease (IBD). The incidence of CDI among hospitalised IBD patients increased from 1% in 1998 to 3% in 2007 with an increase in disease severity. CDI in IBD patients has also been associated with a significant increase in need for colectomy and even mortality with an effect that can persist up to 1 year after the primary infection. However, while a wealth of literature supports this adverse impact of CDI on IBD patients, few have attempted to identify prognostic factors that determine prognostic factors determining severe outcomes associated with CDI in the IBD cohort.
Indeed, there is an important need for such stratification by severity as existing treatment options vary in their comparative effectiveness in mild and severe disease. Metronidazole and vancomycin have traditionally been the agents of choice for treatment of CDI. Early guidelines suggested that most primary infections should be treated with metronidazole with vancomycin reserved for recurrent disease or those unable to tolerate metronidazole, in part due to the cost of vancomycin and concern for spread of vancomycin-resistant bacteria. However, previous studies have demonstrated that while the two agents have comparable efficacy in mild disease, metronidazole is associated with a much greater treatment failure rate in those with severe CDI. Such comparative effectiveness studies in IBD patients are lacking. Retrospective series have reported their experience with both therapies. However, the absence of measures to objectively stratify severity of CDI in IBD patients influences interpretation and generalisability of such results.
We performed this study with the aim of identifying clinical and laboratory factors that predict severe outcomes associated with CDI in IBD patients. Identification of such factors would allow for the development of a quantitative severity score that can be used to inform comparative effectiveness studies and prospective trials of CDI therapy in IBD patients.
Abstract and Introduction
Abstract
Background The increasing incidence of Clostridium difficile (C. difficile) infection (CDI) among patients with inflammatory bowel disease is well recognised. However, most studies have focused on demonstrating that CDI is associated with adverse outcomes in IBD patients. Few have attempted to identify predictors of severe outcomes associated with CDI among IBD patients.
Aim To identify clinical and laboratory factors that predict severe outcomes associated with CDI in IBD patients.
Methods From a multi-institution EMR database, we identified all hospitalised patients with at least one diagnosis code for C. difficile from among those with a diagnosis of Crohn's disease or ulcerative colitis. Our primary outcome was time to total colectomy or death with follow-up censored at 180 days after CDI. Cox proportional hazards models were used to identify predictors of the primary outcome from among demographic, disease-related, laboratory and medication variables.
Results A total of 294 patients with CDI-IBD were included in our study. Of these, 58 patients (20%) met our primary outcome (45 deaths, 13 colectomy) at a median of 31 days. On multivariate analysis, serum albumin <3 g/dL (HR 5.75, 95% CI 1.34–24.56), haemoglobin below 9 g/dL (HR 5.29, 95% CI 1.58–17.69) and creatinine above 1.5 mg/dL (HR 1.98, 95% CI 1.04–3.79) were independent predictors of our primary outcome. Examining laboratory parameters as continuous variables or shortening our primary outcome to include events within 90 days yielded similar results.
Conclusion Serum albumin below 3 g/dL, haemoglobin below 9 g/dL and serum creatinine above 1.5 mg/dL were independent predictors of severe outcomes in hospitalised IBD patients with Clostridium difficile infection.
Introduction
There has been a recent increase in the incidence and severity of Clostridium difficile infection (CDI). Such infections account for an estimated $750 million–$3.2 billion in healthcare costs. While CDI was traditionally linked to antibiotic use or healthcare contact, recent research has identified several new at-risk groups. One such group includes patients with underlying inflammatory bowel disease (IBD). The incidence of CDI among hospitalised IBD patients increased from 1% in 1998 to 3% in 2007 with an increase in disease severity. CDI in IBD patients has also been associated with a significant increase in need for colectomy and even mortality with an effect that can persist up to 1 year after the primary infection. However, while a wealth of literature supports this adverse impact of CDI on IBD patients, few have attempted to identify prognostic factors that determine prognostic factors determining severe outcomes associated with CDI in the IBD cohort.
Indeed, there is an important need for such stratification by severity as existing treatment options vary in their comparative effectiveness in mild and severe disease. Metronidazole and vancomycin have traditionally been the agents of choice for treatment of CDI. Early guidelines suggested that most primary infections should be treated with metronidazole with vancomycin reserved for recurrent disease or those unable to tolerate metronidazole, in part due to the cost of vancomycin and concern for spread of vancomycin-resistant bacteria. However, previous studies have demonstrated that while the two agents have comparable efficacy in mild disease, metronidazole is associated with a much greater treatment failure rate in those with severe CDI. Such comparative effectiveness studies in IBD patients are lacking. Retrospective series have reported their experience with both therapies. However, the absence of measures to objectively stratify severity of CDI in IBD patients influences interpretation and generalisability of such results.
We performed this study with the aim of identifying clinical and laboratory factors that predict severe outcomes associated with CDI in IBD patients. Identification of such factors would allow for the development of a quantitative severity score that can be used to inform comparative effectiveness studies and prospective trials of CDI therapy in IBD patients.
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