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Clostridium difficile was first described as a cause of diarrhea in 1978 and in the last three decades has reached an epidemic state with increasing incidence and severity in both healthcare and community settings. There also has been a rise in severe outcomes from C. difficile infection (CDI). There have been tremendous advancements in the field of CDI with the identification of newer risk factors, recognition of CDI in populations previously thought not at risk and development of better diagnostic modalities. Several treatment options are available for CDI apart from metronidazole and vancomycin, and include new drugs such as fidaxomicin and other options such as fecal microbiota transplantation. This review discusses the epidemiology, risk factors and outcomes from CDI, and focuses primarily on existing and evolving treatment modalities.

AbstractDiarrhea is best defined as passage of loose stools often with more frequent bowel movements. For clinical purposes, theBristolStoolFormScale works well to distinguish stool form and to identify loose stools. Laboratory testing of stool consistency has lagged behind. Acute diarrhea is likely to be due to infection and to be self‐limited. As diarrhea becomes chronic, it is less likely to be due to infection; duration of 1 month seems to work well as a cut‐off for chronic diarrhea, but detailed scientific knowledge is missing about the utility of this definition. In addition to duration of diarrhea, classifications by presenting scenario, by pathophysiology, and by stool characteristics (e.g. watery, fatty, or inflammatory) may help the canny clinician refine the differential diagnosis of chronic diarrhea. In this regard, a careful history remains the essential part of the evaluation of a patient with diarrhea. Imaging the intestine with endoscopy and radiographic techniques is useful, and biopsy of the small intestine and colon for histological assessment provides key diagnostic information. Endomicroscopy and molecular pathology are only now being explored for the diagnosis of chronic diarrhea. Interest in the microbiome of the gut is increasing; aside from a handful of well‐described infections because of pathogens, little is known about alterations in the microbiome in chronic diarrhea. Serological tests have well‐defined roles in the diagnosis of celiac disease but have less clearly defined application in autoimmune enteropathies and inflammatory bowel disease. Measurement of peptide hormones is of value in the diagnosis and management of endocrine tumors causing diarrhea, but these are so rare that these tests are of little value in screening because there will be many more false‐positives than true‐positive results. Chemical analysis of stools is of use in classifying chronic diarrhea and may limit the differential diagnosis that must be considered, but interpretation of the results is still evolving. Breath tests for assessment of carbohydrate malabsorption, small bowel bacterial overgrowth, and intestinal transit are fraught with technical limitations that decrease sensitivity and specificity. Likewise, tests of bile acid malabsorption have had limited utility beyond empirical trials of bile acid sequestrants.

ABSTRACTObjective:Microscopic colitis (MC) is prevalent in adults investigated for chronic watery diarrhea, yet characterization of pediatric MC is limited.Methods:Our pathology database was searched from 1995 to 2011 for pediatric cases of lymphocytic colitis (LC) or collagenous colitis (CC). Those with diarrhea persisting for >2 weeks and visually normal colonoscopy were accepted as cases. Demographics, laboratory results, medication use within 3 months of presentation, medical and family history of autoimmune disease, and response to treatment were abstracted.Results:A total of 27 cases were histologically consistent with MC on biopsy; 5 with concomitant enteric infection or isolated abdominal pain were excluded. Twenty‐two cases of MC (female patients, 59%; median age at diagnosis, 15.3 years) were included (19 LC and 3 CC). Two had type 1 diabetes mellitus, 2 were anti‐nuclear antibody positive, and 2 had common variable immunodeficiency. Of 20 patients who underwent an esophagogastroduodenoscopy, 1 had collagenous sprue and 4 had celiac disease. One presented after the clearance of recurrent Clostridium difficile infection. Previous drug exposures included nonsteroidal anti‐inflammatory drugs (n = 7), proton pump inhibitors (n = 6), and selective serotonin reuptake inhibitors (n = 3). Common symptoms in addition to diarrhea included abdominal pain (77.3%) and weight loss (27.3%). Of 17 patients with follow‐up, all of the 8 treated with steroids had some response: 57.1% (4/7) responded to mesalamine and 42.9% (3/7) responded to bismuth subsalicylate.Conclusions:In this cohort of pediatric patients, LC was much more common than CC. As described in adults, we observed associations with celiac disease, type 1 diabetes mellitus, and medications; we additionally saw an association with immunodeficiency. Our patients showed greater response to steroids than mesalamine or bismuth.

Summary Background Serological markers such as anti‐neutrophil cytoplasmic antibody ( ANCA ) and anti‐ S accharomyces cerevisiae antibody ( ASCA ) may be associated with pouchitis after ileal pouch‐anal anastomosis ( IPAA ). Aim To perform a systematic review with meta‐analysis of studies evaluating the association of ANCA and ASCA status with risk of acute and chronic pouchitis after IPAA . Methods We searched multiple databases (upto S eptember 2012) for studies reporting ANCA and/or ASCA status along with risk of acute or chronic pouchitis after IPAA in adults with ulcerative colitis ( UC ). We abstracted odds ratio ( OR ) or raw data from the individual studies to calculate summary OR estimates with 95% CI s using random‐effects model. Results Eight studies reporting 184 cases of acute pouchitis and six studies reporting 151 cases of chronic pouchitis were included. The odds of chronic pouchitis were 76% higher in ANCA ‐positive patients than ANCA ‐negative (six studies; OR : 1.76; 95% CI : 1.19–2.61; P < 0.01). ASCA‐positivity was not associated with the risk of chronic pouchitis (three studies; OR : 0.89; 95% CI : 0.49–1.59; P = 0.68). Neither ANCA (eight studies; OR : 1.54; 95% CI : 0.79–3.02; P = 0.21) nor ASCA ‐positivity (two studies; OR : 1.28; 95% CI : 0.25–6.54; P = 0.77) were associated with the risk of acute pouchitis. Conclusions The risk of chronic pouchitis after IPAA is higher in ANCA ‐positive patients, but the risk of acute pouchitis is unaffected by ANCA status. ASCA status was not associated with the risk of acute or chronic pouchitis. This information may be used to counsel UC patients regarding their risk of pouchitis after IPAA .

SummaryBackgroundCommunity‐acquired Clostridium difficile infection (CA‐CDI) is an increasingly appreciated condition. It is being described in populations lacking traditional predisposing factors that have been previously considered at low‐risk for this infection. As most studies of CDI are hospital‐based, outcomes in these patients are not well known.AimTo examine outcomes and their predictors in patients with CA‐CDI.MethodsA sub‐group analysis of a population‐based epidemiological study of CDI in Olmsted county, Minnesota from 1991–2005 was performed. Data regarding outcomes, including severity, treatment response, need for hospitalisation and recurrence were analysed.ResultsOf 157 CA‐CDI cases, the median age was 50 years and 75.3% were female. Among all CA‐CDI cases, 40% required hospitalisation, 20% had severe and 4.4% had severe‐complicated infection, 20% had treatment failure and 28% had recurrent CDI. Patients who required hospitalisation were significantly older (64 years vs. 44 years, P < 0.001), more likely to have severe disease (33.3% vs. 11.7%, P = 0.001), and had higher mean Charlson comorbidity index scores (2.06 vs. 0.84, P = 0.001). They had similar treatment failure and recurrence rates as patients who did not require hospitalisation.ConclusionsCommunity‐acquired Clostridium difficile infection can be associated with complications and poor outcomes, including hospitalisation and severe Clostridium difficile infection. As the incidence of community‐acquired Clostridium difficile infection increases, clinicians should be aware of risk factors (increasing age, comorbid conditions and disease severity) that predict the need for hospitalisation and complications in patients with community‐acquired Clostridium difficile infection.