January 12, 2016
In recent years, Clostridium difficile infection (CDI) has emerged as an increasingly common and frequently serious clinical entity.1 In 2011, C difficile was responsible for nearly 500 000 infections and was associated with approximately 29 000 deaths in the United States.2 Since the emergence of hypervirulent strains in the early 2000s, CDI has also become less responsive to standard therapy. Recurrent CDI is particularly problematic; about one-fourth of patients will develop recurrent infection.3 The proportion is even higher among older adults and those with certain comorbidities. In a subset of patients, CDI continues to recur and is often refractory to extended courses of antimicrobial agents. Increasingly, clinicians are using fecal microbiota transplantation (FMT) (“stool transplant”) in these circumstances.1,4
By transplanting donor stool into a patient with recurrent CDI, FMT restores the colonic microbiota to a more healthy state. Successful use of FMT to treat CDI was first reported in 1983.5 Although the procedure initially received slow acceptance, FMT is performed routinely today, especially after recent data demonstrating efficacy of FMT for recurrent CDI.6 At present, the best evidence for FMT is for recurrent CDI, although there is increasing evidence for use in severe, complicated, and refractory CDI.7
Compared with many other medical procedures, FMT is not technologically complicated. However, the actual FMT process is complex because of logistical barriers related to identifying and screening donors and coordinating the timing of stool collection and preparation. Other issues include cost and insurance coverage—who pays for the donor screening and the FMT procedure, especially if performed by colonoscopy? Inconvenience and cost have prevented more widespread use, and, as a result, many patients who might benefit from FMT cannot easily access this therapy. These and other organizational barriers have expanded interest in using frozen stool for FMT.8
Government regulation related to FMT has been another important and difficult hurdle for clinicians. Although the US Food and Drug Administration (FDA) no longer requires an Emergency Investigational New Drug application when FMT is used for treatment of CDI, clinicians are still expected to obtain informed consent from patients.11 However, the regulatory status of central stool banks (such as OpenBiome [Medford, Massachusetts]) that provide frozen stool for use in FMT currently is undergoing revision, as the FDA has published revised draft guidance (now in draft form for nearly 2 years) that, if adopted, would not allow such programs to operate.12Specifically, language in the draft guidance states the donor must be personally known to either the patient or treating physician, a criterion not met by most stool banks.
Although the results reported by Lee et al will likely make FMT more accessible for a larger number of patients, the most fundamental question about recurrent CDI remains—how can clinicians prevent CDI? Antibiotic use is still the strongest predictor for the development of CDI, especially with multiple agents or prolonged use. With about 50% of hospitalized adults receiving antibiotics at any given time,13targeted measures to curtail antimicrobial use remain essential. Recurrent CDI is only one of many poignant reminders of the ongoing need for meaningful investment in antimicrobial stewardship and prevention of health care–associated infection.