The vital roles that intestinal flora, now called microbiota, have in maintaining our health are being increasingly appreciated. Starting with birth, exposure to the outside world begins the ...life-long intimate association our microbiota will have with our diet and environment, and initiates determination of the post-natal structural and functional maturation of the gut. Moreover, vital interactions of the microbiota with our metabolic activities, as well as with the immunological apparatus that constitutes our major defense system against foreign antigens continues throughout life. A perturbed intestinal microbiome has been associated with an increasing number of gastrointestinal and non-gastrointestinal diseases including Clostridium difficile infection (CDI). It has become recognized that fecal microbiota transplantation (FMT) can correct the dysbiosis that characterizes chronic CDI, and effect a seemingly safe, relatively inexpensive, and rapidly effective cure in the vast majority of patients so treated. In addition, FMT has been used to treat an array of other gastrointestinal and non-gastrointestinal disorders, although experience in these other non-CDI diseases is in its infancy. More work needs to be done with FMT to ensure its safety and optimal route of administration. There is a conceptual sea change that is developing in our view of bacteria from their role only as pathogens to that of being critical to health maintenance in a changing world. Future studies are certain to narrow the spectrum of organisms that need to be given to patients to cure disease. FMT is but the first step in this journey.
In the sections below, I will review auscultatory findings (clicks, splashes, peristaltic sounds, peels, arterial bruits, friction rubs, and venous hums) that the stethoscope can detect to reveal ...clues that just might increase our appreciation of pathophysiology, allow prediction of radiologic findings, or perhaps just enable us return to a basic tenet in caring for the patient: a complete examination (Table 1).Table 1. A succussion splash also may be caused by compression of the duodenum between the aorta posteriorly and the superior mesenteric artery (SMA) anteriorly, an entity known as the SMA syndrome (Figure 3). Initially, small bowel obstruction is a dynamic process, beginning with increased peristalsis to overcome the obstruction; this increase is initially heard as more frequent, higher pitched sounds which then diminish and become absent as ileus develops. VASCULATURE Narrowing of any artery can produce a bruit, but in the abdomen, bruits typically are heard over the aorta, splanchnic vessels (celiac artery and SMA), and renal arteries.
Clostridium difficile infection (CDI) has increased to epidemic proportions over the past 15 years, and recurrence rates of 30-65% with failure to respond to multiple courses of antimicrobials are ...common. The aim of this study was to report the efficacy of fecal microbiota transplantation (FMT) in patients with recurrent CDI in five geographically disparate medical centers across the United States.
A multicenter long-term follow-up study was performed on the use of FMT for recurrent CDI. We were able to contact 77 of 94 eligible patients who had colonoscopic FMT for recurrent CDI ≥ 3 months before. Respondents completed a 36-item questionnaire via mail and/or phone that solicited pre-FMT, post-FMT, and donor data. Study outcomes included primary cure rate (resolution of symptoms without recurrence within 90 days of FMT) and secondary cure rate (resolution of symptoms after one further course of vancomycin with or without repeat FMT).
Seventy-three percent of patients were women and the average age was 65 years. The long-term follow-up period ranged from 3 to 68 months between FMT and data collection (mean: 17 months). The majority of patients were living independently at the time of FMT; however, 40% were ill enough to be hospitalized, homebound, or living in a skilled nursing facility. Spouses and partners accounted for 60% of donors and 27% were either first-degree relatives or otherwise related to the patient. The average symptom duration before FMT was 11 months and patients had failed an average of five conventional antimicrobial regimens; nonetheless, 74% of patients had resolution of their diarrhea in ≤ 3 days. Diarrhea resolved in 82% and improved in 17% of patients within an average of 5 days after FMT. The primary cure rate was 91%. Seven patients either failed to respond or experienced early CDI recurrence (≤ 90 days) after FMT. Four of these patients were successfully treated with vancomycin with or without probiotics; two patients were treated unsuccessfully with vancomycin, but subsequent FMT was successful; one patient was not treated and died in hospice care of unclear cause. The secondary cure rate was 98%. All late recurrences of CDI occurred in the setting of antimicrobial therapy for treatment of infections unrelated to C. difficile. In all, 53% of patients stated they would have FMT as their preferred first treatment option if CDI were to recur. While no definite adverse effects of FMT were noted, two patients had improvement in a pre-existing medical condition and four patients developed diseases of potential interest after FMT.
FMT is a rational, durable, safe, and acceptable treatment option for patients with recurrent CDI.
PURPOSE OF REVIEWFecal microbiota transplantation (FMT) re-establishes a balanced intestinal flora with resultant cure of recurrent Clostridium difficile infection (RCDI). FMT has also been used to ...treat other gastrointestinal (GI) diseases including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and chronic constipation and a variety of non-GI disorders. The purpose of this review is to discuss the intestinal microbiota and FMT treatment of GI and non-GI diseases.
RECENT FINDINGSIt is known that an imbalanced intestinal microbiota predisposes to CDI, IBD and IBS. The complex role of intestinal microbiota to maintain health, however, is a newer concept that is being increasingly studied. The microbiome plays an important role in cellular immunity and energy metabolism and has been implicated in the pathogenesis of non-GI autoimmune diseases, chronic fatigue syndrome, obesity and even some neuropsychiatric disorders.
SUMMARYFMT is a highly effective cure for RCDI, but increased knowledge of the intestinal microbiota in health maintenance, as well as controlled trials of FMT in a wide range of disorders are needed before FMT can be accepted and applied clinically.
To date, evidence for the efficacy of fecal microbiota transplantation (FMT) in recurrent Clostridium difficile infection (CDI) has been limited to case series and open-label clinical trials.
To ...determine the efficacy and safety of FMT for treatment of recurrent CDI.
Randomized, controlled, double-blind clinical trial. (ClinicalTrials.gov: NCT01703494).
Two academic medical centers.
46 patients who had 3 or more recurrences of CDI and received a full course of vancomycin for their most recent acute episode.
Fecal microbiota transplantation with donor stool (heterologous) or patient's own stool (autologous) administered by colonoscopy.
The primary end point was resolution of diarrhea without the need for further anti-CDI therapy during the 8-week follow-up. Safety data were compared between treatment groups via review of adverse events (AEs), serious AEs (SAEs), and new medical conditions for 6 months after FMT. Fecal microbiota analyses were performed on patients' stool before and after FMT and also on donors' stool.
In the intention-to-treat analysis, 20 of 22 patients (90.9%) in the donor FMT group achieved clinical cure compared with 15 of 24 (62.5%) in the autologous FMT group (P = 0.042). Resolution after autologous FMT differed by site (9 of 10 vs. 6 of 14 P = 0.033). All 9 patients who developed recurrent CDI after autologous FMT were free of further CDI after subsequent donor FMT. There were no SAEs related to FMT. Donor FMT restored gut bacterial community diversity and composition to resemble that of healthy donors.
The study included only patients who had 3 or more recurrences and excluded those who were immunocompromised and aged 75 years or older.
Donor stool administered via colonoscopy seemed safe and was more efficacious than autologous FMT in preventing further CDI episodes.
National Institute of Diabetes and Digestive and Kidney Diseases.
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