Fecal microbiota transplantation

Recurrent and refractory clostridium difficile infection is a major cause of morbidity and mortality, with recent increase in the number of adults and pediatric patients affected worldwide.

Standard therapy with oral metronidazole or vancomycin is increasingly associated with failure, and disease recurrence has been described it up to 30% of patients after the first episode and up to 60% after two or more recurrences.

FMT refers to the infusion of feces from a healthy donor into a recipient patient’s G.I. tract, with the aim to restore normal gut microbiota in diseases or infections associated with bacterial disruption.

Recommended for the treatment of recurrent C. difficile infection.

The emergence of a virulent strain of the organism (NAP1/BI/027) is associated even with a higher rate of treatment failure.

Fidaxomicin reduces the rate of recurrence compared with vancomycin.

Refers to the transfer of normal intestinal flora from a healthy donor to a person with intestinal dysbiosis.

The procedure is more than 90% effective in resolving relapsing and recurrent C. Difficile infection (van Nood E et al ).

During the procedure a fecal slurry from a healthy donor stool is administered by colonoscope, enema, nasogastric, or nasoduodenal tube or capsule.

The majority of procedures have been performed with fresh school suspensions from related donors.

In a study using frozen FMT capsules from unrelated donors to patients with recurrent C. difficile infection, there was no alteration in adverse events or rates of resolution of diarrhea (Youngster I et al).

Fecal microbiota transplantation (FMT) has been shown to be effective in treating relapsing or refractory Clostridium difficile infection, but practical barriers and safety concerns have prevented its widespread use.

Twenty patients (median age, 64.5 years; range, 11-89 years) with at least 3 episodes of mild to moderate C difficile infection and failure of a 6- to 8-week taper with vancomycin or at least 2 episodes of severe C difficile infection requiring hospitalization were enrolled.

Healthy volunteers were screened as potential donors and FMT capsules were generated and stored at -80°C (-112°F).

Patients received 15 capsules on 2 consecutive days and were followed up for symptom resolution and adverse events for up to 6 months.

No serious adverse events attributed to FMT were observed.

Overall 90% rate of clinical resolution of diarrhea, with a daily number of bowel movements decreased from a median of 5 the day prior to administration to 2 at day 3 and 1 at 8 weeks.

The majority of FMT procedures have been performed with fresh stool suspensions from related donors.

Fresh donations requires prior identification and screening of a suitable donor precluding the use of FMT in acute situations.

The limited viability of fresh samples is usually estimated to 6 hours, making screening of donors and donation impractical.

Use of frozen FMT inocula from healthy volunteer donors for treating CDI and using nasogastric tube administration of a frozen inoculum is comparable with colonoscopic delivery of inocula.

It has been demonstrated that oral administration of frozen encapsulated fecal material from unrelated donors to treat patients with recurrent CDI, has an overall rate of clinical resolution of diarrhea of 90% comparable with rates reported previously using fresh stool preparations.

In a comparison of frozen versus fresh fecal transplant for recurrent or refractory C difficile infection similar proportion of patients had clinic resolution of diarrhea at 13 weeks (Lee CH et al).

Frozen fecal microbiota transplant has the advantage of being less costly with the reduction in the number frequency of donor screenings, immediate availability, possibility of delivering FMT at centers that do not have on-site laboratory facilities.

Molecular typing has demonstrated 10-50% of recurrent CDI may be attributable to reinfections rather than recurrence of the initial infection, suggesting a perturbed microbiota may play a role in facilitating reinfection.

Time to resolution of symptoms is longer when delivered orally compared to when the inoculum is administered with colonoscope or by nasogastric tube.

May be effective in treating ulcerative colitis.

It is not effective in IBS.

FMT is associated with complications including inflammatory, infectious and procedural difficulties.

FMT may be associated with gram-negative bacteremia period.

Fecal microbiota transplantation caries risk of transmission of undetected or emerging pathogens that may lead to hospitalization or death.


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