Ashwin N. Ananthakrishnan

Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections.

Clostridium difficile infection (CDI) is a leading cause of hospital-associated gastrointestinal illness and places a high burden on our health-care system. Patients with CDI typically have extended lengths-of-stay in hospitals, and CDI is a frequent cause of large hospital outbreaks of disease. This guideline provides recommendations for the diagnosis and management of patients with CDI as well as for the prevention and control of outbreaks while supplementing previously published guidelines. New molecular diagnostic stool tests will likely replace current enzyme immunoassay tests. We suggest treatment of patients be stratified depending on whether they have mild-to-moderate, severe, or complicated disease. Therapy with metronidazole remains the choice for mild-to-moderate disease but may not be adequate for patients with severe or complicated disease. We propose a classification of disease severity to guide therapy that is useful for clinicians. We review current treatment options for patients with recurrent CDI and recommendations for the control and prevention of outbreaks of CDI.

Excess hospitalisation burden associated with Clostridium difficile in patients with inflammatory bowel disease

Background: Clostridium difficile is an important cause of diarrhoea in hospitalised patients. An increasing number of cases of C difficile colitis occur in patients with inflammatory bowel disease (IBD)—Crohn’s disease (CD), ulcerative colitis (UC). Objective: To estimate the potential excess morbidity and mortality associated with C difficile in hospitalised patients with IBD. Methods: Data from the Nationwide Inpatient Sample (2003) were analysed and outcomes were examined of patients hospitalised with both C difficile colitis and IBD compared with those hospitalised for either condition alone. The primary outcome was in-hospital mortality. A subgroup analysis was also performed comparing outcomes of C difficile infection in patients with CD and UC. Results: 2804 discharges were diagnosed as having both C difficile and IBD, 44 400 as having C difficile alone, and 77 366 as having IBD alone. On multivariate analysis, patients in the C difficile–IBD group had a four times greater mortality than patients admitted to hospital for IBD alone (aOR = 4.7, 95% CI 2.9 to 7.9) or C difficile alone (aOR = 2.2, 95% CI 1.4 to 3.4), and stayed in the hospital for three days longer (95% CI 2.3 to 3.7 days). Significantly higher mortality, endoscopy and surgery rates were found in patients with UC compared with CD (p<0.05), but no significant difference in length of stay or median hospital charge between the two groups was seen. Conclusions: C difficile colitis is associated with a significant healthcare burden in hospitalised patients with IBD and carries a higher mortality than in patients with C difficile without underlying IBD.

Clostridium difficile infection: epidemiology, risk factors and management.

The epidemiology of Clostridium difficile infection (CDI) has changed over the past decade. There has been a dramatic worldwide increase in its incidence, and new CDI populations are emerging, such as those with community-acquired infection and no previous exposure to antibiotics, children, pregnant women and patients with IBD. Diagnosis of CDI requires identification of C. difficile toxin A or B in diarrheal stool. The accuracy of current diagnostic tests remains inadequate and the optimal diagnostic testing algorithm has not been defined. The first-line agents for CDI treatment are metronidazole and vancomycin, with the latter being the preferred agent in patients with severe disease as it has significantly superior efficacy. The incidence of metronidazole treatment failures has increased, emphasizing the need to find alternative treatment options. Disease recurrence continues to occur in 20–40% of patients and its treatment remains challenging. In patients with CDI who develop fulminant colitis, early surgical consultation is essential. Intravenous immunoglobulin and tigecycline have been used in patients with severe refractory disease but delaying surgery may be associated with worse outcomes. Infection control measures are key to prevent horizontal transmission of infection. Ongoing research into effective treatment protocols and prevention is essential.

Clostridium difficile and inflammatory bowel disease.

Clostridium difficile colitis has doubled in North America over the past 5 years and recent reports have demonstrated an increase in incidence and severity of these infections in patients with inflammatory bowel disease (IBD; Crohns disease, ulcerative colitis). Studies from single institutions as well as trends identified in nationwide inpatient databases have shown that IBD patients with concomitant C. difficile infection experience increased morbidity and mortality. Results from our center have shown that over half of C. difficile-infected IBD patients will require hospitalization and the colectomy rate may approach 20%. Because C. difficile colitis will both mimic and precipitate an IBD flare, it is essential that clinicians be vigilant to identify and address this infectious complication, as empiric treatment with corticosteroids without appropriate antibiotics may precipitate deterioration. The majority of IBD patients appear to contract C. difficile as outpatients, and a prior history of colitis appears to be the most significant risk factor for acquiring this infection. In addition to C. difficile colitis, IBD patients are now known to be at risk for C. difficile enteritis as well as infections in reconstructed ileoanal pouches. An additional challenge facing C. difficile infections in IBD patients is the decreased efficacy of metronidazole, and the need for oral vancomycin in patients requiring hospitalization. In this review we summarize the present knowledge regarding C. difficile infection in the setting of IBD, including unique clinical scenarios facing IBD patients, diagnostic algorithms, and treatment approaches.

Vitamin D deficiency in patients with inflammatory bowel disease: association with disease activity and quality of life.

BACKGROUND Vitamin D deficiency is common in inflammatory bowel disease (IBD). The aim of the study was to determine the prevalence and predictors of vitamin D deficiency in an IBD cohort. It was hypothesized that vitamin D deficiency is associated with increased disease activity and lower health-related quality of life (HRQOL). METHODS This was a retrospective cohort study. Harvey-Bradshaw index and ulcerative colitis disease activity index were used to assess disease activity. Short Inflammatory Bowel Disease Questionnaire scores were used to assess HRQOL. Multivariate logistic regression was used to identify independent predictors of vitamin D deficiency and its association with disease activity and HRQOL. RESULTS The study included 504 IBD patients (403 Crohns disease [CD] and 101 ulcerative colitis [UC]) who had a mean disease duration of 15.5 years in CD patients and 10.9 years in UC patients; 49.8% were vitamin D deficient, with 10.9% having severe deficiency. Vitamin D deficiency was associated with older age (P = .004) and older age at diagnosis (P = .03). Vitamin D deficiency was associated with lower HRQOL (regression coefficient -2.21, 95% confidence interval [CI], -4.10 to -0.33) in CD but not UC (regression coefficient 0.41, 95% CI, -2.91 to 3.73). Vitamin D deficiency was also associated with increased disease activity in CD (regression coefficient 1.07, 95% CI, 0.43 to 1.71). CONCLUSIONS Vitamin D deficiency is common in IBD and is independently associated with lower HRQOL and greater disease activity in CD. There is a need for prospective studies to assess this correlation and examine the impact of vitamin D supplementation on disease course.

Long-term intake of dietary fat and risk of ulcerative colitis and Crohn's disease

Introduction Dietary fats influence intestinal inflammation and regulate mucosal immunity. Data on the association between dietary fat and risk of Crohns disease (CD) and ulcerative colitis (UC) are limited and conflicting. Methods We conducted a prospective study of women enrolled in the Nurses’ Health Study cohorts. Diet was prospectively ascertained every 4 years using a validated semi-quantitative food frequency questionnaire. Self-reported CD and UC were confirmed through medical record review. We examined the effect of energy-adjusted cumulative average total fat intake and specific types of fat and fatty acids on the risk of CD and UC using Cox proportional hazards models adjusting for potential confounders. Results Among 170 805 women, we confirmed 269 incident cases of CD (incidence 8/100 000 person-years) and 338 incident cases of UC (incidence 10/100 000 person-years) over 26 years and 3 317 338 person-years of follow-up. Cumulative energy-adjusted intake of total fat, saturated fats, unsaturated fats, n-6 and n-3 polyunsaturated fatty acids (PUFAs) were not associated with risk of CD or UC. However, greater intake of long-chain n-3 PUFAs was associated with a trend towards lower risk of UC (HR 0.72, 95% CI 0.51 to 1.01). In contrast, high long-term intake of trans-unsaturated fatty acids was associated with a trend towards an increased incidence of UC (HR 1.34, 95% CI 0.94 to 1.92). Conclusions A high intake of dietary long-chain n-3 PUFAs may be associated with a reduced risk of UC. In contrast, high intake of trans-unsaturated fats may be associated with an increased risk of UC.

Inflammatory bowel disease in the elderly is associated with worse outcomes: A national study of hospitalizations

Background: Inflammatory bowel disease (IBD) has a bimodal peak of incidence with ≈15% of the cases manifesting after 65 years. Previous reports on the outcomes of IBD in the elderly have been single‐center studies or have predated the use of biologics. The aim of our study was to compare outcomes of IBD‐related hospitalizations in a nationwide representative cohort of patients 65 years and older with younger patients. Methods: This was a cross‐sectional study utilizing data from the Nationwide Inpatient Sample (NIS) for the year 2004. We identified all IBD‐related hospitalizations through the presence of the appropriate ICD‐9‐CM codes for Crohns disease, ulcerative colitis, or associated complications. We compared the differences in disease presentation as well the frequency of utilization of different interventions. We calculated the adjusted odds of mortality in older compared to the younger IBD patients using multivariate logistic regression. Results: Patients older than 65 years accounted for ≈25% of all IBD‐related hospitalizations in 2004. They were less likely to be hospitalized with fistulizing (4.0 versus 8.8%, P < 0.001) or stricturing disease (4.0 versus 5.8%, P = 0.001). Even after adjusting for comorbidity, they had higher in‐hospital mortality (odds ratio [OR] 3.91, 95% confidence interval [CI] 2.50–6.11). Older patients with fistulizing disease are more likely to undergo surgery (OR 1.55, 95% CI 1.00–2.40). Among IBD patients who underwent surgery, older patients also had a longer postoperative stay (1.73 days, 95% CI 1.04–2.21). Conclusions: Older patients with IBD‐related hospitalizations have substantial morbidity and higher mortality than younger patients. Further research is needed to better characterize the natural history and treatment outcomes in this cohort.

Outcomes of Weekend Admissions for Upper Gastrointestinal Hemorrhage: A Nationwide Analysis

BACKGROUND & AIMS Previous studies have identified a weekend effect in outcomes of patients with various medical conditions suggesting worse outcomes for weekend admissions. The aim of our study was to analyze if weekend admissions for upper gastrointestinal hemorrhage (UGIH) have higher mortality and longer hospital stay compared with those admitted on weekdays, and to examine if this effect differs by hospital teaching status. METHODS This was a cross-sectional study using the Nationwide Inpatient Sample 2004. A total of 28,820 discharges with acute variceal hemorrhage (AVH) and 391,119 discharges with acute nonvariceal UGIH (NVUGIH) were identified through appropriate International Classification of Diseases, ninth edition codes. Admissions were considered to be weekend admissions if they were admitted between midnight on Friday through midnight on Sunday. In-hospital mortality, frequency, and timing of endoscopy were measured. RESULTS On multivariate analysis, NVUGIH patients admitted on weekends had higher adjusted in-hospital mortality (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.09-1.35) and were less likely to undergo early endoscopy within 1 day of hospitalization (OR, 0.64; 95% CI, 0.61-0.68). Weekend admission was not predictive of in-hospital mortality in patients with AVH (OR, 0.94; 95% CI, 0.75-1.18), but was associated with lower likelihood of early endoscopy in nonteaching hospitals (OR, 0.65; 95% CI, 0.51-0.82). Early endoscopy was associated with significantly shorter hospital stays (NVUGIH, -1.08 days; AVH, -2.35 days) and lower hospitalization charges (NVUGIH, -

Normalization of plasma 25-hydroxy vitamin D is associated with reduced risk of surgery in Crohn's disease.

1958; AVH, -

Review article: vitamin D and inflammatory bowel diseases

8870). CONCLUSIONS Patients with NVUGIH admitted on the weekend had higher mortality and lower rates of early endoscopy. Patient with AVH admitted to nonteaching hospitals also had lower utilization of early endoscopy, but no difference in survival. There is a need for research into identifying the reasons for the weekend effect.