Fecal Microbiota Transplantation for Recurrent CDI

Clostridium difficile (also called C. dif) infection is a growing epidemic with increasing rates of recurrence, severity and mortality. According to the Agency for Healthcare Research and Quality, the national rate of hospitalization with CDI listed as any diagnosis has increased from 5.6 per 1,000 discharges in 2001 to 12.7 per 1,000 discharges in 2011, and rates are projected to increase. The Centers for Disease Control and Prevention identifies CDI as one of the highest threats to human health and indicates immediate and aggressive action is needed to prevent this infection.

Despite effective treatment, 6%-25% of diagnosed patients experience a recurrent episode; subsequent recurrence can be seen in 65% of patients who have two or more recurrences. Treatment of recurrent or refractory CDI is a major challenge for patients and clinicians due to limited treatment options.

Fecal microbiotia transplantation is a new form of treatment. North Kansas City Hospital is developing an FMT protocol for selected patients with CDI, that should be finalized in the coming months.

Hospitalization Rates for CDI

FMT Premise

The gastrointestinal microbiota plays an integral part in the maintenance of gut homeostasis. While the pathophysiologic features of recurrent CID are not fully understood, it likely involves dysbiosis, an imbalance of the gut microbiota. Patients with recurrent CDI have been shown to have significant disruption of the intestinal microbiome. Several factors may be responsible for this imbalance, but the most important one is antibiotic use. The premise of FMT is to reintroduce a healthy diversity of bacteria to the affected patient, thereby preventing Clostridium difficile from becoming the dominant organism and breaking the cycle of recurrent CDI.

Promising Horizon

While not routinely practiced or widely available, FMT has great promise in the treatment of refractory and recurrent CDI. FMT is not a new therapeutic modality as reference of fecal suspension dates back to 4th century China. It has only been in the past few years that interest in FMT by patients, researchers, and industry has surged. Bala S. Somayaji, MD, an infectious disease physician with Infectious Disease Associates of KC, PC, supports fecal microbiota transplantation option for appropriately selected patients with recurrent or relapsing CDI infections. “While we are encouraged by the high efficacy rates of FMT reported for recurrent CDI, we continue to watch the literature for new developments,” Dr. Somayaji said.

A workgroup at NKCH, led by Monika Totoraitis, Pharm.D, is developing an FMT protocol. Prescribing FMT will be restricted to infectious disease and gastrointestinal providers.

Alteration to Gut Microbiota

Indications for FMT

  • Recurrent or relapsing CDI
    • At least three episodes of mild to moderate CDI that have not responded to treatment
    • At least two episodes of severe CDI resulting in hospitalization
  • Severe CDI with no response to standard therapy for a minimum of 48 hours

Opportunities for CDI prevention include judicious use of antibiotics and evaluating the need to initiate and/or continue acid suppressing therapy.

Risk Factors for CID

  • Antibiotic exposure
    • Minimizing use of multiple and high risk antibiotics
    • Fluoroquinolones have an association with the emergence of the hypervirulent NAP1 Clostridium difficile
  • Hospitalization or prolonged length of stay
  • Advanced age and underlying comorbidity
  • Acid suppressing medications such as proton pump inhibitors

Exclusions for FMT Per Protocol

  • Presence of anatomic contraindication to colonoscopy
  • Pregnancy
  • Significant compromised immunity
  • Immunosuppressive medications
  • Recent chemotherapy
  • Decompensated liver cirrhosis
  • Advanced human immunodeficiency virus (CD4 count < 250 cells/uL)
  • Neutropenia with absolute neutrophil count < 1000/uL
  • History of a significant allergy to specific foods such as tree nuts, eggs, peanuts, shellfish

Sourcing and Instillation

While the source of fecal microbiota may be obtained from a known or unknown donor, NKCH has elected to utilize unrelated-donor samples provided through a stool bank. Utilizing a stool bank increases the availability of the FMT product and decreases the cost of screening individual donors. Prospective stool donors undergo a rigorous screening process. Donors are screened with a comprehensive evaluation of their medical history, behavioral risks and current health status. Additionally, serological and stool-based assays are performed to determine whether infectious pathogens are present.

Fecal microbiota instillation may be administered through the upper intestinal tract (via oral capsules or nasogastric or nasoduodenal tube) or the lower tract (via colonoscopy or retention enema). There is no consensus on the preferred route of administration. FMT administration at NKCH will initially be limited to the lower gastrointestinal route via colonoscopy.

Side Effects

Common side effects reported following FMT include nausea and vomiting, abdominal cramps, low grade temperature, diarrhea and constipation. Long-term side effects, including transmission of an infectious pathogen or noninfectious diseases are not fully understood and require further investigation and long-term follow-up studies.

FDA Involvement

FDA guidance permits the use of FMT to treat CDI not responsive to standard therapies provided that informed consent is obtained and the patient is thoroughly informed of its risks and benefits, and understands FMT is classified as an investigational treatment.

With limited treatment options available for recurrent CDI, FMT provides an additional option for selected patients. Current evidence showing FMT to be an effective treatment for those patients with recurrent CDI is encouraging. Watch for additional information as NKCH finalizes its FMT protocol and prepares to accept patients.

Bala S. Somayaji, MD

Bala S Somayaji, MDDr. Somyaji earned her medical degree and completed an anesthesiology residency at Berhampur University, India. She also completed an internal medicine residency at the University of Tennessee and an infectious disease fellowship at The University of Kansas Medical Center.

Her medical interests include invasive bloodstream infections, hospital epidemiology, HIV, treatment of opportunistic infections, immunocompromised patients and systemic mycosis.