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Fecal microbiota transplantation for recurrent C difficile infection: Ready for prime time?

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ABSTRACTRecurrent Clostridium difficile infection has been a major challenge for patients and clinicians. Recurrence of infection after treatment with standard antibiotics is becoming more common with the emergence of more-resistant strains of C difficile. Fecal microbiota transplantation is an alternative treatment for recurrent C difficile infection, but it is not yet widely used.

KEY POINTS

  • Fecal microbiota transplantation involves instilling gut microbiota from a healthy donor into the diseased gut of a patient who has recurrent or recalcitrant episodes of diarrhea despite antibiotic treatment for C difficile infection. The instillation can be done via nasogastric tube, endoscope, or enema.
  • Donor screening is necessary to prevent transmission of communicable diseases to the recipient.
  • Recently published studies indicate that this procedure is effective for treating recurrent C difficile infection. Randomized clinical trials to assess its efficacy and safety are underway.
  • The field of microbiota therapy is rapidly progressing. More physicians are learning to embrace the concept of fecal microbiota transplantation, and patients are beginning to overcome the “yuck factor” and accept its benefits.


 

References

If you had a serious disease, would you agree to an alternative treatment that was cheap, safe, and effective—but seemed disgusting? Would you recommend it to patients?

Such a disease is recurrent Clostridium difficile infection, and such a treatment is fecal microbiota transplantation—instillation of blenderized feces from a healthy donor (ideally, the patient’s spouse or “significant other”) into the patient’s colon to restore a healthy population of bacteria.1,2 The rationale behind this procedure is simple: antibiotics and other factors disrupt the normal balance of the colonic flora, allowing C difficile to proliferate, but the imbalance can be corrected by reintroducing the normal flora.1

In this article, we will review how recurrent C difficile infection occurs and the importance of the gut microbiota in resisting colonization with this pathogen. We will also describe the protocol used for fecal microbiota transplantation.

C DIFFICILE INFECTION OFTEN RECURS

C difficile is the most common cause of hospital-acquired diarrhea and an important cause of morbidity and death in hospitalized patients.3,4 The cost of this infection is estimated to be more than $1.1 billion per year and its incidence is rising, partly because of the emergence of more-virulent strains that make treatment of recurrent infection more difficult.5,6

C difficile infection is characterized by diarrhea associated with findings suggestive of pseudomembranous colitis or, in fulminant cases, ileus or megacolon.7 Recurrent C difficile infection is defined as the return of symptoms within 8 weeks after successful treatment.7

C difficile produces two types of toxins. Toxin A is an enterotoxin, causing increased intestinal permeability and fluid secretion, while toxin B is a cytotoxin, causing intense colonic inflammation. People who have a poor host immune response to these toxins tend to develop more diarrhea and colonic inflammation.8

A more virulent strain of C difficile has emerged. Known as BI/NAP1/027, this strain is resistant to quinolones, and it also produces a binary toxin that has a partial gene deletion that allows for increased production of toxins A and B in vitro.9,10 More cases of severe and recurrent C difficile infection have been associated with the increasing number of people infected with this hypervirulent strain.9,10

C difficile infection recurs in about 20% to 30% of cases after antibiotic treatment for it, usually within 30 days, and the risk of a subsequent episode doubles after two or more occurrences.10,11 Metronidazole (Flagyl) and vancomycin are the primary treatments; alternative treatments include fidaxomicin (Dificid), 10 rifaximin (Xifaxan),12 nitazoxanide,13 and tolevamer (a novel polymer that binds C difficile toxins).14

Table 1 summarizes the treatment regimen for C difficile infection in adults, based on clinical practice guidelines from the US Centers for Disease Control and Prevention (CDC).7

THE NORMAL GUT MICROBIOTA KEEPS PATHOGENS OUT

Immediately after birth, the sterile human gut becomes colonized by a diverse community of microorganisms.15 This gut microbiota performs various functions, such as synthesizing vitamin K and vitamin B complex, helping digest food, maintaining the mucosal integrity of the gut, and priming the mucosal immune response to maintain homeostasis of commensal microbiota.16

However, the most important role of the gut microbiota is “colonization resistance” or preventing exogenous or potentially pathogenic organisms from establishing a colony within the gut.17 It involves competition for nutrients and occupation of binding sites on the gut epithelium by indigenous flora.16 Other factors such as the mucosal barrier, salivation, swallowing, gastric acidity, desquamation of mucosal membrane cells, intestinal motility, and secretion of antibodies also play major roles in colonization resistance.17

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