Faecal microbiota transplantation for eradicating carriage of multidrug-resistant organisms: a systematic review.

BACKGROUND: Multidrug-resistant (MDR) microorganism development in the gut is frequently the result of inappropriate antibiotic use. Faecal microbiota transplantation (FMT) restores normal gut microbiota in patients with Clostridium difficile infection. We hypothesized that it may help in decolonizing MDR organisms (MDROs) and in preventing recurrent MDR infections. OBJECTIVES: To assess FMT efficacy (eradication rate) for decolonizing MDROs and preventing recurrent MDR infections. DATA SOURCES: Medline, Embase and Web of Science (inception through 11 February 2019). STUDY ELIGIBILITY CRITERIA: Clinical trials, retrospective studies, case reports and case series. PARTICIPANTS: Patients with MDR infections or MDRO colonization treated with FMT. INTERVENTIONS: FMT. METHODS: Systematic review. RESULTS: Twenty-one studies (one randomized clinical trial, seven uncontrolled clinical trials, two retrospective cohort studies, two case series, nine case reports) assessing 192 patients were included. Three studies assessed FMT efficacy in preventing MDR infections; 16 assessed its effect on MDRO colonization; two assessed both. Data from 151 patients were included in the final analyses. In studies with low to moderate risk of bias, the eradication rate was 37.5% to 87.5%. Efficacy was similar in studies looking at infection or colonization and did not differ by length of follow-up. No serious adverse events from FMT were reported. Seven patients died of other causes. CONCLUSIONS: FMT could be used as a treatment for eradicating MDR colonization and possibly preventing recurrent MDR infections, once more supporting efficacy and safety data are available. Larger well-designed randomized controlled trials are needed to further explore this therapy.

Immune modulator therapy for microscopic colitis in a case series of 73 patients.

BACKGROUND: Microscopic colitis (MC) is a common cause of chronic diarrhoea. Various treatment options have been described, but there are limited data describing outcomes of corticosteroid-sparing treatments. AIM: To evaluate the outcomes of patients with active MC treated with immune modulators. METHODS: All patients seen at Mayo Clinic, Rochester between January 1, 1997 and November 30, 2016 with a histological diagnosis of MC were identified. Patients treated with an immune modulator of interest were selected and clinical outcomes recorded. RESULTS: Seventy-three MC patients (50 collagenous colitis and 23 lymphocytic colitis) with a median disease duration of 24 months (range, 7-60) were included. The indications for treatment were budesonide-refractoriness in 66%, budesonide dependence in 29%, and budesonide intolerance in 5%. Median age was 51.8 years (range, 43.4-63.1) and 61 (84%) were female. Thiopurines were used in 49 patients (67%) for a median of 4 months (range, 1.5-15). Complete and partial response occurred in 43% and 22% respectively. Adverse effects resulting in therapy cessation occurred in 17 patients (35%). Twelve patients (16%) were treated with methotrexate for a median of 14 months (3-18.8). Complete and partial response occurred in 58% and 17%, respectively. Anti-TNF therapy was used in 10 patients (14%) for a median of 4 months (range, 2.3-5.5). Complete response occurred in four patients and partial response in four patients. CONCLUSIONS: The majority of patients with active MC responded to thiopurines, methotrexate, or anti-TNF therapy. Larger controlled studies are required to confirm the efficacy and safety of these medications in MC.

High risk of post-infectious irritable bowel syndrome in patients with Clostridium difficile infection.

BACKGROUND: Infectious enteritis is a commonly identified risk factor for irritable bowel syndrome (IBS). The incidence of Clostridium difficile infection (CDI) is on the rise. However, there is limited information on post-infectious IBS (PI-IBS) development following CDI and the host- and infection-related risk factors are not known. AIM: To determine the incidence and risk factors for PI-IBS following CDI. METHODS: A total of 684 cases of CDI identified from September 2012 to November 2013 were surveyed. Participants completed the Rome III IBS questionnaire and details on the CDI episode. Predictive modelling was done using logistic regression to evaluate risk factors for PI-IBS development. RESULTS: A total of 315 CDI cases responded (46% response rate) and 205 were at-risk (no pre-CDI IBS) for PI-IBS development. A total of 52/205 (25%) met the Rome III criteria for IBS ≥6 months following CDI. IBS-mixed was most common followed by IBS-diarrhoea. In comparison to those without subsequent PI-IBS, greater percentage of PI-IBS patients had CDI symptoms >7 days, nausea, vomiting, abdominal pain during CDI, anxiety and a higher BMI. Using logistic regression, CDI symptoms >7 days [Odds ratio (OR): 2.96, P = 0.01], current anxiety (OR: 1.33, P < 0.0001) and a higher BMI (OR: 1.08, P = 0.004) were independently associated with PI-IBS development; blood in the stool during CDI was protective (OR: 0.44, P = 0.06). CONCLUSIONS: In this cohort study, new-onset IBS is common after CDI. Longer CDI duration, current anxiety and higher BMI are associated with the diagnosis of C. difficile PI-IBS. This chronic sequela should be considered during active management and follow-up of patients with CDI.

Clostridium difficile infection after restorative proctocolectomy and ileal pouch anal anastomosis for ulcerative colitis.

AIM: Clostridium difficile infection (CDI) of the ileal pouch following restorative proctocolectomy (RPC) is becoming increasingly recognized. We aimed to understand better (i) the associated risk factors, (ii) treatment practices and (iii) the pouch diversion and failure rate in patients who developed CDI of the pouch after RPC for ulcerative colitis (UC). METHOD: Patients who tested positive for C. difficile of the pouch between 2007 and 2010 were included in the analysis. Data collected included patient demographics, time from RPC to documented CDI, the treatment of CDI and rate of excision of the pouch. RESULTS: Of 2785 patients recorded in the hospital CDI database, 15 had had an RPC with ileal pouch anal anastomosis. The median age was 44 years and the median interval from RPC to first documented episode of CDI was 3 years. Thirteen (81%) patients had had multiple episodes of pouchitis before and after CDI infection, and all were symptomatic at the time of testing for CDI. Within 30 days of the diagnosis of CDI, six (40%) patients were taking immunosuppressive medication, seven (47%) were taking a proton pump inhibitor and 12 (80%) had received antibiotics. Five patients required hospitalization for CDI and four had severe infections characterized by a serum creatinine more than 1.5 times baseline (n = 3) and a white cell count above 15 000 (n = 1). Six patients who underwent endoscopy had severe inflammation of the pouch including the presence of a pseudomembrane in one case. Ten patients were treated with metronidazole alone and five with vancomycin. Two patients had recurrent CDI of the pouch during a median follow-up period of 2.9 years and one had CDI refractory to medical management. This patient required diversion of the pouch with an ileostomy for refractory CDI but no patient required excision of the pouch. CONCLUSION: All 15 patients developing CDI of the pouch were successfully treated with antibiotics and only one required surgery in the form of an ileostomy.

Clinical predictors of recurrent Clostridium difficile infection in out-patients.

BACKGROUND: Clostridium difficile infection (CDI) recurs in 20-30% of patients. AIM: To describe the predictors of recurrence in out-patients with CDI. METHODS: Out-patient cases of CDI in Olmsted County, MN residents diagnosed between 28 June 2007 and 25 June 2010 were identified. Recurrent CDI was defined as recurrence of diarrhoea with a positive C. difficile PCR test from 15 to 56 days after the initial diagnosis with interim resolution of symptoms. Patients who had two positive tests within 14 days were excluded. Cox proportional hazard models were used to assess the association of clinical variables with time to recurrence of CDI. RESULTS: The cohort included 520 out-patients; 104 had recurrent CDI (cumulative incidence of 17.5% by 30 days). Univariate analysis identified increasing age and antibiotic use to be associated with recurrent CDI. Severe CDI, peripheral leucocyte count and change in serum creatinine >1.5-fold were not. In a multiple variable model, concomitant antibiotic use was associated with risk of recurrent CDI (HR = 5.4, 95% CI 1.6-17.5, P = 0.005), while age (HR per 10 year increase = 1.1, 95% CI 0.9-1.3, P = 0.22); peripheral leucocyte count >15 × 10(9) /L (HR = 1.0, 95% CI 0.5-2.1, P = 0.92); and change in serum creatinine greater than 1.5-fold (HR = 0.8, 95% CI 0.4-1.5, P = 0.44) were not. CONCLUSIONS: Antibiotic use was independently associated with a dramatic risk of recurrent Clostridium difficile infection in an out-patient cohort. It is important to avoid unnecessary systemic antibiotics in patients with Clostridium difficile infection, and patients with ongoing antibiotic use should be monitored closely for recurrent infection.

The fate of indefinite and low-grade dysplasia in ulcerative colitis and primary sclerosing cholangitis colitis before and after liver transplantation.

BACKGROUND: Patients with primary sclerosing cholangitis (PSC) and ulcerative colitis (UC) are at an increased risk of colorectal neoplasia, but it is unknown if liver transplantation (LT) alters neoplasia progression. AIM: To examine the natural history of indefinite dysplasia (IND) and low-grade dysplasia (LGD) that develop in patients with PSC-UC with and without LT. METHODS: We performed a retrospective review of patients with PSC and UC evaluated at our institution between 1993 and 2011 who were diagnosed with IND or LGD before or after LT for PSC. The primary end point was neoplasia progression or persistent LGD. RESULTS: Ninety-six patients (non-LT n = 63, LT n = 33) were examined. For the IND group, multifocal lesions were significantly associated with time to neoplasia progression [hazard ratio (HR), 3.5; 95% confidence interval (CI), 1.3-9.7], while 5-aminosalicylate (5-ASA) use was protective (HR, 0.2; 95% CI, 0.1-0.6). For patients with LGD, multifocal lesions were significantly associated with the primary end point (HR, 7.1; 95% CI, 1.7-28.3), while LT was protective (HR, 0.3; 95% CI, 0.1-0.9). CONCLUSIONS: In PSC-UC patients with IND, 5-ASA use was associated with a decreased the risk of neoplasia progression, regardless of transplant status. In contrast, multifocal IND and LGD were associated with neoplasia progression or persistent LGD. Patients who developed LGD following LT for PSC were less likely to have progressive neoplasia or persistent LGD, compared with those who had not been transplanted.

Meta-analysis: serological markers and the risk of acute and chronic pouchitis.

BACKGROUND: Serological markers such as anti-neutrophil cytoplasmic antibody (ANCA) and anti-Saccharomyces 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 September 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% CIs 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.

Natalizumab for moderate to severe Crohn's disease in clinical practice: the Mayo Clinic Rochester experience.

BACKGROUND: Not all patients with Crohn's disease (CD) respond or maintain response to anti-tumor necrosis factor (TNF) agents and alternative treatment is necessary. Natalizumab, a monoclonal antibody to alpha-4 integrin approved for CD, has demonstrated efficacy in randomized clinical trials. We describe our experience with natalizumab in clinical practice at Mayo Clinic Rochester. METHODS: Consecutive patients prescribed natalizumab for active CD were invited to participate and were followed prospectively. Incidence of infection, hospitalization, neoplasm, or other adverse events were recorded. Clinical activity was assessed using the Harvey-Bradshaw Index at each 30-day infusion visit. RESULTS: Between April 2008 and September 2010, 36 patients were prescribed natalizumab and 30 (83.3%) agreed to participate. Median disease duration was 9 years (range, 3-43). Twenty-three patients had prior exposure to two anti-TNF agents, seven to one agent. All patients experienced at least one adverse event; none of the 13 patients in whom natalizumab was stopped (43%) discontinued due to adverse events. Five patients had infusions held for infection. No patient developed progressive multifocal leukoencephalopathy (PML). Fourteen patients (46%) had clinical response. The cumulative probability of achieving complete response within 1 year was 56% (28%-73%). Four of seven patients were weaned off corticosteroids. CONCLUSIONS: In our experience with natalizumab in clinical practice, adverse events were manageable and did not result in treatment cessation. No PML cases were seen and clinical response was similar to that in clinical trials. Natalizumab results in clinical benefit in patients who have active disease and have failed anti-TNF therapy.

Outcomes in community-acquired Clostridium difficile infection.

BACKGROUND: Community-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. AIM: To examine outcomes and their predictors in patients with CA-CDI. METHODS: A 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. RESULTS: Of 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. CONCLUSIONS: Community-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.

Review article: Microscopic colitis--lymphocytic, collagenous and 'mast cell' colitis.

BACKGROUND: Microscopic colitis is a relatively common cause of chronic diarrhoea in predominantly older adults, traditionally termed lymphocytic colitis and collagenous colitis. Increased mast cells found in the colonic biopsies of some patients with chronic diarrhoea may represent a distinct type of microscopic colitis. AIM: To provide an updated review of the epidemiology, diagnosis and treatment of microscopic colitis, and to discuss the role of mast cells in the gastrointestinal tract and their potential role in cases of functional diarrhoea. METHOD: A MEDLINE literature search was performed to identify pertinent articles. Relevant clinical abstracts were also reviewed. RESULTS: Incidence rates of microscopic colitis (lymphocytic and collagenous colitis) have increased over time, to levels comparable with other forms of inflammatory bowel disease. The possibility of drug-induced microscopic colitis and concomitant coeliac sprue are important considerations when evaluating these patients. There are few controlled treatment trials in microscopic colitis, with much of the data on treatment coming from retrospective studies. Mast cells have been implicated in functional bowel disorders, with increased mast cells possibly contributing to cases of otherwise unexplained chronic diarrhoea, although this concept requires further investigation. CONCLUSIONS: In patients with microscopic colitis, a systematic approach to therapy often leads to satisfactory control of symptoms. The role of mast cells in chronic diarrhoea represents an evolving field, with the potential to offer alternative treatment pathways in patients with otherwise unexplained functional diarrhoea.

What do gastroenterology trainees want: recognition, remuneration or recreation?

BACKGROUND: Occupational psychologists have identified three factors important in motivating physicians: financial reward, academic recognition, time off. AIM: To assess motivators among gastroenterology (GI) trainees. METHODS: A questionnaire was distributed to GI trainees to assess their motivators: (1) work fewer hours for less lucrative rate, (2) reduction in salary/increase in hours for academic protected time, and (3) work longer hours for higher total salary, but less lucrative hourly rate. RESULTS: Overall, 61 trainees responded; 52% of trainees would work shorter hours for less lucrative rate; 60% would accept a disproportionate reduction in salary/increase in hours for academic protected time; 54% would work longer hours for more money but less lucrative rate. Most trainees (93%) accepted at least one scenario. CONCLUSIONS: Most GI trainees are willing to modify their job description to align with their personal values. Tailoring job descriptions according to these values can yield economic benefits to GI Divisions.

Endoscopy in the management of patients after ileal pouch surgery for ulcerative colitis.

Pouchitis is the most common complication following ileal pouch-anal anastomosis in patients with ulcerative colitis. However, there are several other inflammatory and noninflammatory conditions that can mimic pouchitis, and endoscopy with biopsies is essential for distinguishing these various conditions. This paper will review the differential diagnosis of pouchitis and the role of endoscopy in the diagnosis and management of disorders of the ileal pouch.

Age at onset of inflammatory bowel disease and the risk of surgery for non-neoplastic bowel disease.

BACKGROUND: There is conflicting data regarding the response to medical and surgical therapy for inflammatory bowel disease with respect to age at disease onset. AIM: To determine if the age at onset of Crohn's disease and ulcerative colitis is a risk factor for surgery for non-neoplastic bowel disease. METHODS: This was a case-control study of patients evaluated between 1998 and 2001. Cases had undergone an initial operation for bowel disease. Controls were matched 1:1 for gender, disease subtype, date of first visit (+/-2 years), time from diagnosis prior to first visit (+/-3 years) and duration of follow-up. Association with age, disease extent, smoking history, medication use and co-morbidities vs. case/control status was assessed using multiple variable conditional logistic regression to estimate the odds ratio (OR) and 95% confidence intervals (CI) for undergoing surgery. RESULTS: Among 132 Crohn's patients, older patients had lower odds for surgery (OR per 5 years, 0.86; 95% CI: 0.75-0.98). The rate of surgery for non-neoplastic bowel disease was not significantly associated with disease distribution, co-morbidities or cigarette smoking. Among 234 ulcerative colitis patients, the rate of surgery was unrelated to age, disease extent, co-morbidities or cigarette smoking, CONCLUSIONS: For Crohn's disease, but not ulcerative colitis, the risk of surgery for non-neoplastic bowel disease decreases with increasing age at diagnosis, irrespective of disease distribution and history of cigarette smoking.

Systematic review: the management of pouchitis.

Pouchitis is the most common complication following proctocolectomy and ileal pouch-anal anastomosis in patients with ulcerative colitis. We aim at discussing relevant information on epidemiology, clinical features, risk factors, diagnostic testing, differential diagnosis and treatment of this idiopathic inflammatory condition. A computerized search of PubMed was performed with the search term 'pouchitis', limited to English papers on humans. This strategy identified 514 references. Relevant articles were selected from this list. In addition, the reference list for each of the selected articles was reviewed to identify any additional references. Pouchitis occurs in up to 60% of patients after ileal pouch-anal anastomosis for ulcerative colitis, and has characteristic clinical, endoscopic and histological features. The most important test for diagnosis is pouch endoscopy with biopsy. Antibiotics remain the mainstay of treatment, and other options are discussed for those patients who are refractory to antibiotic therapy.

Review article: drug-induced microscopic colitis - proposal for a scoring system and review of the literature.

The pathophysiology of microscopic colitis is unknown, although it is thought to be because of an abnormal immune reaction to luminal antigens in predisposed hosts. Specific antigens have not been proved, although various infectious triggers and drugs have been proposed. The responsibility of several drugs has been questioned, some with strong clinical and/or histological evidence suggesting causality. The issue of drug-induced microscopic colitis is important because of the burden of this disease. Thus, any case that can be cured by withdrawal of a drug must be identified. In this report, we propose a scoring system for drug-induced microscopic colitis, adapting existing criteria of drug causality, and review the literature using this framework. Based on this review, several drugs are identified with intermediate or high likelihood of inducing microscopic colitis. Finally, we suggest how to treat individual patients suspected of having drug-induced colitis according to the level of evidence for that particular drug.

Gender-related differences in slowing colonic transit by a 5-HT3 antagonist in subjects with diarrhea-predominant irritable bowel syndrome.

OBJECTIVE: To evaluate the influence of gender on the effect of a 5-HT3 antagonist, alosetron, 1 mg b.i.d., on GI and colonic transit in D-IBS. METHODS: Thirty patients (15 male, 15 female) with D-IBS received 1 mg b.i.d. alosetron for 6 wk. Transit was measured by scintigraphy at baseline and at the end of treatment. RESULTS: Alosetron, 1 mg b.i.d., significantly retarded small bowel and, proximal and overall colonic transit in the 30 patients with D-IBS. The effect of alosetron on the primary endpoint, colonic geometric center at 24 h, was significantly greater in females than in males (p < 0.05). However, two females showed no slowing of colonic transit on treatment. Among male patients, two of 15 had a slowing of colonic transit at 24 h that was greater than the mean change in female patients, suggesting responsiveness to alosetron among a subgroup of males. CONCLUSION: A 5-HT3 antagonist, alosetron, significantly retards small intestinal and colonic transit in diarrhea-predominant IBS patients, with significantly greater female to male responsiveness. Gender partly contributes to differences in the serotonergic control of intestinal and colonic transit in patients with D-IBS.