Stephen M. Vindigni

Fecal Microbiota Transplant for Treatment of Clostridium difficile Infection in Immunocompromised Patients

OBJECTIVES:Patients who are immunocompromised (IC) are at increased risk of Clostridium difficile infection (CDI), which has increased to epidemic proportions over the past decade. Fecal microbiota transplantation (FMT) appears effective for the treatment of CDI, although there is concern that IC patients may be at increased risk of having adverse events (AEs) related to FMT. This study describes the multicenter experience of FMT in IC patients.METHODS:A multicenter retrospective series was performed on the use of FMT in IC patients with CDI that was recurrent, refractory, or severe. We aimed to describe rates of CDI cure after FMT as well as AEs experienced by IC patients after FMT. A 32-item questionnaire soliciting demographic and pre- and post-FMT data was completed for 99 patients at 16 centers, of whom 80 were eligible for inclusion. Outcomes included (i) rates of CDI cure after FMT, (ii) serious adverse events (SAEs) such as death or hospitalization within 12 weeks of FMT, (iii) infection within 12 weeks of FMT, and (iv) AEs (related and unrelated) to FMT.RESULTS:Cases included adult (75) and pediatric (5) patients treated with FMT for recurrent (55%), refractory (11%), and severe and/or overlap of recurrent/refractory and severe CDI (34%). In all, 79% were outpatients at the time of FMT. The mean follow-up period between FMT and data collection was 11 months (range 3–46 months). Reasons for IC included: HIV/AIDS (3), solid organ transplant (19), oncologic condition (7), immunosuppressive therapy for inflammatory bowel disease (IBD; 36), and other medical conditions/medications (15). The CDI cure rate after a single FMT was 78%, with 62 patients suffering no recurrence at least 12 weeks post FMT. Twelve patients underwent repeat FMT, of whom eight had no further CDI. Thus, the overall cure rate was 89%. Twelve (15%) had any SAE within 12 weeks post FMT, of which 10 were hospitalizations. Two deaths occurred within 12 weeks of FMT, one of which was the result of aspiration during sedation for FMT administered via colonoscopy; the other was unrelated to FMT. None suffered infections definitely related to FMT, but two patients developed unrelated infections and five had self-limited diarrheal illness in which no causal organism was identified. One patient had a superficial mucosal tear caused by the colonoscopy performed for the FMT, and three patients reported mild, self-limited abdominal discomfort post FMT. Five (14% of IBD patients) experienced disease flare post FMT. Three ulcerative colitis (UC) patients underwent colectomy related to course of UC >100 days after FMT.CONCLUSIONS:This series demonstrates the effective use of FMT for CDI in IC patients with few SAEs or related AEs. Importantly, there were no related infectious complications in these high-risk patients.

C. difficile Infection: Changing Epidemiology and Management Paradigms

The incidence of Clostridium difficile infection (CDI) has been rising in hospitals, long-term care facilities, and within the community. Cases have been more severe with more complications, deaths, and higher healthcare-associated costs. With the emergence of a hypervirulent strain of C. difficile and the increasing prevalence of community-acquired CDI among healthy patients without traditional risk factors, the epidemiology of C. difficile has been evolving. This changing epidemiology requires a change in management. Taking into account new risk factors for CDI and growing subpopulations of affected individuals, diagnostic, treatment, and prevention approaches need to be adjusted.

The intestinal microbiome, barrier function, and immune system in inflammatory bowel disease: a tripartite pathophysiological circuit with implications for new therapeutic directions

We discuss the tripartite pathophysiological circuit of inflammatory bowel disease (IBD), involving the intestinal microbiota, barrier function, and immune system. Dysfunction in each of these physiological components (dysbiosis, leaky gut, and inflammation) contributes in a mutually interdependent manner to IBD onset and exacerbation. Genetic and environmental risk factors lead to disruption of gut homeostasis: genetic risks predominantly affect the immune system, environmental risks predominantly affect the microbiota, and both affect barrier function. Multiple genetic and environmental ‘hits’ are likely necessary to establish and exacerbate disease. Most conventional IBD therapies currently target only one component of the pathophysiological circuit, inflammation; however, many patients with IBD do not respond to immune-modulating therapies. Hope lies in new classes of therapies that target the microbiota and barrier function.

Alteration of the intestinal microbiome: fecal microbiota transplant and probiotics for Clostridium difficile and beyond.

Clostridium difficile infection is increasingly common with a high risk of recurrence despite antibiotic treatment. In cases of recurrent C. difficile infection, fecal microbiota transplant (FMT) is a highly effective treatment option promoting the restoration of normal gut microbiota. Furthermore, preliminary uncontrolled evidence demonstrates possible benefit of FMT in the management of some cases of inflammatory bowel disease and chronic constipation. In addition to presenting an overview of FMT, we discuss the role of probiotics, a more common approach to modifying the intestinal microbiome. Probiotics have been utilized broadly for many disease processes, including gastrointestinal, cardiovascular and allergic disease settings, although with limited and inconsistent results. Multiple potential areas for research are also identified.

The gut microbiome: a clinically significant player in transplantation?

The intestinal microbiome is critical to digestion, metabolism and protection from pathogenic organisms. Dysbiosis, or alteration of this microbiome, can result in Clostridium difficile infection and may play a role in other conditions. Patients undergoing solid organ transplantation (e.g., kidney, lung, liver, small bowel) and hematopoietic stem cell transplantation have a shift in the gut microbiome with a decrease in predominant organisms, a loss of bacterial diversity and emergence of a new dominant population. This translates into increased morbidity and mortality with risk of infection and rejection. We discuss the changes seen in the microbiome and its possible consequences. It may be important to develop strategies to restore the normal microbiome in such patients.

Fecal Microbiota Transplantation

Fecal microbiota transplantation (FMT) is the transfer of stool from a healthy donor into the colon of a patient whose disease is a result of an altered microbiome, with the goal of restoring the normal microbiota and thus curing the disease. The most effective and well-studied indication for FMT is recurrent Clostridium difficile infection. At this time, there is insufficient evidence to recommend FMT for other gastrointestinal diseases, but studies are under way. There is also insufficient evidence to recommend FMT for nongastrointestinal diseases at this time. The field is rapidly emerging.

Stool transplant for the senior citizen: Is it safe?

Fecal microbiota transplantation (FMT), also known as stool ransplant, involves placing healthy donor stool into the colon of n affected individual in order to restore the normal colonic microiota. It is an efficacious, cost-effective treatment for recurrent lostridium difficile infection (CDI) that has been unresponsive to tandard therapy. The use of this treatment modality has become ncreasingly popular, particularly as we are seeing an epidemic f CDI with escalating incidence, more severe clinical presentaions, and higher morbidity and mortality. Some cases of CDI may e community-acquired without previously common risk factors, uch as antibiotic use. The simplicity and efficacy of a “natural” pproach is appealing. CDI has always been more common in the elderly population over age 65) and 91% of all CDI-related deaths occur in this age ohort [1,2]. Additionally, while elderly patients are at increased isk of developing CDI, they are also at increased risk of severe, evere and complicated, or recurrent CDI which is more difficult o treat and often results in multiple hospitalizations, prolonged reatment courses, and higher morbidity and mortality. Several tudies have shown the elderly to have a less diverse gut microiome which may make their colon more susceptible to C. difficile olonization, subsequent toxin production and resulting disease. his is an ongoing area of research. The most important risk factors or development of CDI in the elderly are presented in Table 1. For patients with multiply recurrent disease who have not esponded to adequate antibiotic regimens, FMT is a potential treatent option. What do we know about the safety and efficacy of FMT n the elderly? A multi-center, retrospective study by Agrawal et al. evaluated he long-term efficacy and safety of FMT in 146 elderly patients aged ≥65) with recurrent, severe, or severe and complicated CDI

Cirrhosis and C. difficile: A Deadly Duo?

Patients with advanced liver disease develop complications as their disease progresses, including hepatic encephalopathy, ascites, spontaneous bacterial peritonitis (SBP), and variceal bleeding.Moreover, they have decreased life expectancywith high rates of mortality related to infection, bleeding, and multi-organ failure, including the hepatorenal syndrome. Patients with cirrhosis are also at increased risk of developing Clostridium difficile infection (CDI) with several identified risk factors including frequent hospitalizations, regular use of antibiotics for prophylaxis or treatment for SBP, proton pump inhibitor (PPI) use, and anoverall immunocompromised state. In a study of the impact of CDI on inpatients with cirrhosis, Bajaj et al. [1] reported increased mortality, longer hospitalization, and higher hospitalization charges in patients with both cirrhosis and CDI compared to patients with either cirrhosis or CDI alone (p\ 0.001). Since patients with cirrhosis and CDI have a higher mortality, Saab and colleagues addressed the question of whether screening patients with cirrhosis on admission to the hospital, with isolation and treatment to eradicate C. difficile, will decrease mortality and healthcare costs [2]. In this issue of Digestive Diseases and Sciences, they published the results of a two-arm study using a Markov decision analysis model to compare this strategy with testing and treating only symptomatic patients with diarrhea. The authors report that the screen and treat strategy improved healthcare outcomes with a significant cost-savings and decrease in healthcare utilization. They projected a decrease in CDI-related mortality and a 3.54-fold reduced cost in the screening group. Their interpretation and resultant recommendation is to implement a C. difficile screening program targeted at hospitalized patients with cirrhosis. While this recommendation is interesting, it contradicts important points documented in two current published guidelines, that is, (1) test-only diarrheal stools and (2) do not treat C. difficile carriers [3, 4]. We shall now discuss these points in more detail.

Hospital resuscitation teams: a review of the risks to the healthcare worker

Background“Code blue” events and related resuscitation efforts involve multidisciplinary bedside teams that implement specialized interventions aimed at patient revival. Activities include performing effective chest compressions, assessing and restoring a perfusing cardiac rhythm, stabilizing the airway, and treating the underlying cause of the arrest. While the existing critical care literature has appropriately focused on the patient, there has been a dearth of information discussing the various stresses to the healthcare team. This review summarizes the available literature regarding occupational risks to medical emergency teams, characterizes these risks, offers preventive strategies to healthcare workers, and highlights further research needs.MethodsWe performed a literature search of PubMed for English articles of all types (randomized controlled trials, case-control and cohort studies, case reports and series, editorials and commentaries) through September 22, 2016, discussing potential occupational hazards during resuscitation scenarios. Of the 6266 articles reviewed, 73 relevant articles were included.ResultsThe literature search identified six potential occupational risk categories to members of the resuscitation team—infectious, electrical, musculoskeletal, chemical, irradiative, and psychological. Retrieved articles were reviewed in detail by the authors.ConclusionOverall, we found there is limited evidence detailing the risks to healthcare workers performing resuscitation. We identify these risks and offer potential solutions. There are clearly numerous opportunities for further study in this field.

Role of Endoscopy in Diagnosis of Crohn’s Disease and Chronic Ulcerative Colitis

While multiple diagnostic studies are often necessary to diagnose inflammatory bowel disease (IBD), endoscopy is still considered the gold standard. Endoscopy is critical in the initial evaluation and necessary to exclude other etiologies that can present with similar signs and symptoms. Endoscopy, defined as colonoscopy with ileoscopy and esophagogastroduodenoscopy (EGD), provides the most accurate assessment of disease extent and severity. Colonoscopy with ileoscopy is essential for the initial diagnosis of IBD. While EGD is not necessary in all patients, it can provide significant information, particularly in evaluating Crohn’s disease. The role of endoscopy in the diagnosis of IBD with key endoscopic findings will be detailed in this chapter.