Faecal Microbiota Transplantation for the Treatment of Recurrent Clostridium difficile Infection

Current Promise and Future Needs

Mark J. Koenigsknecht; Vincent B. Young

Disclosures

Curr Opin Gastroenterol. 2013;29(6):628-632. 

In This Article

Abstract and Introduction

Abstract

Purpose of review The use of faecal microbiota transplantation (FMT) as treatment for recurrent Clostridium difficile infection (CDI) has increased rapidly over the past few years. In this review, we highlight clinical studies of FMT for treatment of recurrent CDI and discuss the safety, standardization and future of this treatment option. The major risk factor for CDI is prior antibiotic use, which results in an altered state of the gut microbiota characterized by decreased microbial diversity. This altered gut microbiota increases the patient's susceptibility to CDI. In patients with recurrent CDI, the microbiota remains in a state with decreased diversity, and FMT from a healthy individual restores the gut microbiota and subsequently colonization resistance against the pathogen.

Recent findings Recent studies have shown the success rate for FMT as treatment for recurrent CDI being greater than 90%. Standardized, frozen preparations of faeces can be used, which increases the availability of faeces for FMT and decreases the cost of screening individual donors. In addition, there have been recent advances in identifying a defined microbial community isolated from faeces that can restore colonization resistance against C. difficile.

Summary The use of FMT is a successful treatment for recurrent CDI when primary treatment options have failed. However, more work needs to define potential long-term consequences of this treatment and understand how specific members of the gut microbiota can restore colonization resistance against C. difficile.

Introduction

In recent years, a new focus has been put on Clostridium difficile due to the emergence of hyperendemic strains that have led to outbreaks around the world and an increasing incidence of disease.[1] C. difficile is an anaerobic, spore-forming, Gram-positive bacilli and is now the leading cause of hospital-acquired infections, surpassing methicillin-resistant Staphylococcus aureus (MRSA).[2] In hospitals, C. difficile infection (CDI) is the number one cause of pseudomembranous colitis and significant nosocomial diarrhoea cases.[3] CDI is responsible for significant morbidity, mortality and increased economic burden in hospitalized patients, approaching 5 billion dollars annually.[4,5] Risk for the development of CDI is associated with the use of broad spectrum antibiotic therapy as well as increasing patient age and hospitalization.[6] As many as 50% of people become colonized with C. difficile after a 4-week hospital stay.[7,8] Furthermore, with a relapse rate approaching 25%, CDI can significantly increase hospital costs on the basis of extended stays alone.[9] The risk of developing recurrent CDI increases with each recurrence event.[6] There is a 40% risk for an additional recurrence with one prior CDI and a greater than 60% risk with two prior CDIs.[10,11] In a subset of patients, CDI recurrences can become refractory to standard antimicrobial therapy, which has led to a search for alternative treatments for refractory disease. One old but recently popular alternative therapy is faecal microbiota transplantation (FMT) in which the faecal microbiota from a healthy host is transferred to a patient with recurrent CDI in order to restore the microbiota to a resistant state against CDI.[12]

Establishment of a healthy gut microbiota is critical in order to resolve the symptoms of recurrent CDI. The gut microbiota provides multiple benefits to the host, one of which is to mediate colonization resistance against gut pathogens.[13,14] The first modern use of FMT was described in 1958 as a treatment for pseudomembranous enterocolitis.[15] However, accounts of FMT date all the way back to fourth century China where it was used to treat severe diarrhoea.[16] An altered gut microbiota after antibiotic treatment can be restored to a community that is resistant to CDI via FMT. The use of FMT for the treatment of recurrent CDI has been shown to be a well tolerated and effective treatment when primary treatment options have failed. As the recurrence rate of CDI increased over the last decade, so has the interest in FMT for the treatment of recurrent CDI. The previous year resulted in multiple comprehensive reviews on FMT describing use for treatment of a variety of diseases,[17] the preparation and screening of faeces,[18] and outcomes in clinical use for treatment of recurrent CDI.[19] The purpose of this review is to highlight recent advances in the use of FMT for recurrent CDI, describe potential concerns from this treatment and to identify areas of future research.

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