Fecal microbiota transplantation in treating Clostridium difficile infection

Clostridium difficile infection (CDI) is an increasingly common and severe international health problem. Customary treatment of this infection, usually with antibiotics, is often ineffective and its recurrence is common. In recent years the treatment of recurrent or refractory CDI by the transfer of stool from an uninfected person, so called fecal “microbiota transplantation” has become recognized as effective and generally safe. The effectiveness of this novel treatment is incompletely defined but is likely to be due to its correction of the intestinal dysbiosis that characterizes the disease. Practical methods for the administration of the transplantation have been described. This review summarizes the current reported experiences with fecal microbiota transplantation in the treatment for CDI.     

Fecal microbiota transplantation for recurrent Clostridium difficile infection in hematopoietic stem cell transplant recipients

Recurrent Clostridium difficile infection (CDI) is a consequence of intestinal dysbiosis and is particularly common following hematopoietic stem cell transplantation (HSCT). Fecal microbiota transplantation (FMT) is an effective method of treating CDI by correcting intestinal dysbiosis by passive transfer of healthy donor microflora. FMT has not been widely used in immunocompromised patients, including HSCT recipients, owing to concern for donor‐derived infection. Here, we describe initial results of an FMT program for CDI at a US HSCT center. Seven HSCT recipients underwent FMT between February 2015 and February 2016. Mean time post HSCT was 635 days (25–75 interquartile range [IQR] 38–791). Five of the patients (71.4%) were on immunosuppressive therapy at FMT; 4 had required long‐term suppressive oral vancomycin therapy because of immediate recurrence after antibiotic cessation. Stool donors underwent comprehensive health and behavioral screening and laboratory testing of serum and stool for 32 potential pathogens. FMT was administered via the naso‐jejunal route in 6 of the 7 patients. Mean follow‐up was 265 days (IQR 51–288). Minor post‐FMT adverse effects included self‐limited bloating and urgency. One patient was suspected of having post‐FMT small intestinal bacterial overgrowth. No serious adverse events were noted and all‐cause mortality was 0%. Six of 7 (85.7%) patients had no recurrence; 1 patient recurred at day 156 post FMT after taking an oral antibiotic and required repeat FMT, after which no recurrence has occurred. Diarrhea was improved in all patients and 1 patient with gastrointestinal graft‐versus‐host disease was able to taper off systemic immunosuppression after FMT. With careful donor selection and laboratory screening, FMT appears to be a safe and effective therapy for CDI in HSCT patients and may confer additional benefits. Larger studies are necessary to confirm safety and efficacy and explore other possible effects.     

Fecal microbiota transplantation for fulminant Clostridium difficile infection in an allogeneic stem cell transplant patient

We present a case of severe Clostridium difficile infection (CDI) in a non‐neutropenic allogeneic hematopoietic stem cell transplant recipient who was treated successfully with fecal microbiota therapy after standard pharmacologic therapy had failed. Following naso‐jejunal instillation of donor stool, the patient's symptoms resolved within 48 h. Bowel resection was averted. This is the first case in the literature, to our knowledge, to describe fecal microbiota therapy in a profoundly immunocompromised host with severe CDI. We propose that fecal microbiota therapy be considered as a therapeutic option in immunosuppressed patients with refractory severe CDI.     

Fecal calprotectin in management of Clostridium difficile infection: a longitudinal study

Background: Clostridium difficile infection (CDI) is characterized by a relevant intestinal neutrophil infiltrate. So far, role of fecal calprotectin in CDI, has been investigated only in few studies, mainly focused on diagnosis of the disease.

Aim: By a longitudinal design, we assess fecal calprotectin concentrations (FCCs) in subjects with CDI, evaluating the correlation between fecal marker and response to therapy.

Methods: Clinical (diarrhea scoring) and laboratory (FCCs and leucocytes count) evaluation was performed in 56 subjects with CDI at time of diagnosis (T₀) and after a week from starting of therapy (T₁). Clinical response to therapy at T₁ was related with both T₀ and T₁ FCC values. FCCs were also related to all-cause 30-day mortality, recurrence and death, both of them within 90 days.

Results: FCCs at T₁ were significantly increased in subjects with persistence of diarrhea in respect to the other ones (285.5?±?270 µg/g vs 150.7?±?147 µg/g, respectively; p?T₀ than patients who responded. No correlation was found among FCCs, both at T₀ and T₁, and the other outcomes.

Conclusions: Longitudinal evaluation of FCCs in patients with CDI could support physicians in clinical management of disease, for example in term of duration (10 vs 14 days) or type (first vs second line therapy). Further and larger studies could confirm the eventual role of this marker in prognostic algorithms, mainly in prediction of recurrence.     

Complicated fecal microbiota transplantation in a tetraplegic patient with severe Clostridium difficile infection

A 65-year-old male suffering from acute spinal cord injury leading to incomplete tetraplegia presented with severe recurrent Clostridium difficile(C. difficile) infection subsequent to antibiotic treatment for pneumonia. After a history of ineffective antimicrobial therapies, including metronidazole, vancomycin, fidaxomicin, rifaximin and tigecycline, leading to several relapses, the patient underwent colonoscopic fecal microbiota transplantation from his healthy son. Four days subsequent to the procedure, the patient showed a systemic inflammation response syndrome. Without detecting an infectious cause, the patient received antimicrobial treatment, including tigecycline, metronidazole, vancomycin via polyethylene glycol and an additional enema for a period of seven days, leading to a prompt recovery and no reported C. difficile infection relapse during a 12 wk follow up.     

Systematic review of intestinal microbiota transplantation (fecal bacteriotherapy) for recurrent Clostridium difficile infection

Clostridium difficile infection (CDI) is a gastrointestinal disease believed to be causally related to perturbations to the intestinal microbiota. When standard treatment has failed, intestinal microbiota transplantation (IMT) is an alternative therapy for patients with CDI. IMT involves infusing intestinal microorganisms (in a suspension of healthy donor stool) into the intestine of a sick patient to restore the microbiota. However, protocols and reported efficacy for IMT vary. We conducted a systematic literature review of IMT treatment for recurrent CDI and pseudomembranous colitis. In 317 patients treated across 27 case series and reports, IMT was highly effective, showing disease resolution in 92% of cases. Effectiveness varied by route of instillation, relationship to stool donor, volume of IMT given, and treatment before infusion. Death and adverse events were uncommon. These findings can guide physicians interested in implementing the procedure until better designed studies are conducted to confirm best practices.     

Fecal microbiota transplantation and Clostridioides difficile infection among privately insured patients in the United States

Journal of Gastroenterology - Clostridioides difficile infection (CDI) may be rising in severity in the US over the past decade and its treatment landscape is changing given the recent adoption of...     

Physician attitudes toward the use of fecal microbiota transplantation for the treatment of recurrent Clostridium difficile infection

BACKGROUND:

Fecal microbiota transplantation (FMT) is a safe and effective, yet infrequently used therapy for recurrent Clostridium difficile infection (CDI).

OBJECTIVE:

To characterize barriers to FMT adoption by surveying physicians about their experiences and attitudes toward the use of FMT.

METHODS:

An electronic survey was distributed to physicians to assess their experience with CDI and attitudes toward FMT.

RESULTS:

A total of 139 surveys were sent and 135 were completed, yielding a response rate of 97%. Twenty-five (20%) physicians had treated a patient with FMT, 10 (8%) offered to treat with FMT, nine (7%) referred a patient to receive FMT, and 83 (65%) had neither offered nor referred a patient for FMT. Physicians who had experience with FMT (performed, offered or referred) were more likely to be male, an infectious diseases specialist, >40 years of age, fellowship trained and practicing in an urban setting. The most common reasons for not offering or referring a patient for FMT were: not having ‘the right clinical situation’ (33%); the belief that patients would find it too unappealing (24%); and institutional or logistical barriers (23%). Only 8% of physicians predicted that the majority of patients would opt for FMT if given the option. Physicians predicted that patients would find all aspects of the FMT process more unappealing than they would as providers.

CONCLUSIONS:

Physicians have limited experience with FMT despite having treated patients with multiple recurrent CDIs. There is a clear discordance between physician beliefs about FMT and patient willingness to accept FMT as a treatment for recurrent CDI.     

A case of Clostridium difficile infection complicated by acute respiratory distress syndrome treated with fecal microbiota transplantation

Acute respiratory distress syndrome is a life-threatening disorder caused mainly by pneumonia. Clostridium difficile infection (CDI) is a common nosocomial diarrheal disease. Disruption of normal intestinal flora by antibiotics is the main risk factor for CDI. The use of broad-spectrum antibiotics for serious medical conditions can make it difficult to treat CDI complicated by acute respiratory distress syndrome. Fecal microbiota transplantation is a highly effective treatment in patients with refractory CDI. Here we report on a patient with refractory CDI and acute respiratory distress syndrome caused by pneumonia who was treated with fecal microbiota transplantation.