Fecal Microbiota Transplants: A Cost-Effective Solution to A High-Burden Infection

What is C. Difficile?

Clostridium difficile (C. difficile) is a bacterium that colonizes the body’s gastrointestinal (GI) tract. C. difficile spreads through spores released by the bacterium that are incredibly resistant to extreme environmental factors such as drastic temperature changes, surfaces colonized by other bacterium, and a large variety of disinfectant cleaning agents. C. difficile infects a new host when a susceptible individual touches a surface contaminated by spores and then exposes their GI system to these spores, typically through hand to mouth contact.  

Many individuals carry C. difficile in their bodies and are perfectly healthy and asymptomatic their whole lives. However, C. difficile becomes a problem when individuals are treated with antibiotics. Antibiotics wipe out not only the targeted pathogen for which the patient is receiving treatment, but also other bacteria in the body that compete with C. difficile for energy and nutrients. C. difficile is often resistant to many antibiotics, and this depletion of competitors allows it to spread and colonize the GI tract completely.

In individuals with weakened immune systems, C. difficile infection (CDI) can lead to complications. Infection is triggered by toxins released by C. difficile and symptoms can range from diarrhea to severe colon inflammation that can lead to perforation of the colon, toxic megacolon, and sepsis (infection of the bloodstream). Thankfully, treatments for C. difficile do exist, like the antibiotic vancomycin to which it is very susceptible. However, as we have learned in the past, antibiotic resistance is a growing threat, and C. difficile may develop resistance to vancomycin in the future, increasing the urgency for the development of new treatment options.  

Disease Burden and Standard Treatment

The incidence and severity of CDI has increased over the past decade, and is a growing worldwide health problem associated with substantial health care costs and significant morbidity and mortality.1 While C. difficile-associated diarrhea usually occurs in elderly and hospitalized patients with recent antibiotic use,2 clinicians have seen a growing number of infections in previously low-risk populations, such as younger and healthy individuals without a history of antibiotic use.3 In 2011, C. difficile caused almost half a million cases in the United States. An estimated 83,000 of these cases had at least one recurrence of the infection, and there were about 29,000 deaths.4 The 2014 economic cost of CDI in the United States was $5.4 million, mostly due to hospitalization.5

C. difficile is typically treated with antibiotics; metronidazole and vancomycin are the two most commonly used ones. Metronidazole is usually preferred for mild-to-moderate CDI due to its low cost compared to vancomycin ($2 per day vs. $71-143 per day). In severe and complicated cases, a combination of vancomycin and metronidazole are administered to patients. In 2011, a third antibiotic, fidaxomicin, was approved for treatment of mild-to-moderate CDI. However, common recurrence of CDI following standard antibiotic treatment highlights the importance of alternative treatment both to reduce recurrent infections, and contribute to antibiotic stewardship.

An Alternative Treatment: Fecal Microbiota Transplants

Fecal microbiota transplants (FMTs) increasingly have become recognized as a cost-effective treatment for recurrent CDI, and were first used in 1983.6 FMTs take stool from a healthy individual and instill it into a patient with CDI to re-establish a healthy gut ecosystem with a balanced bacterial makeup to prevent the growth of harmful bacteria.7 FMTs are more cost-effective than the current standard antibiotic treatment for combating CDIs. One study found that FMTs cost $6,897 per quality-adjusted life year (QALY), compared to the antibiotic treatment with vancomycin which cost $16,119 to $27,393 per QALY.8,9

A meta-analysis of 18 different observational studies found that FMTs were successfully treated 92.1% of CDIs.10 Because FMTs are so effective at treating recurrent CDIs, the Infectious Diseases Society of America (IDSA) and the Society for Healthcare Epidemiology of America updated their C. difficile treatment guidelines in February, 2018, to include FMTs.

A Future for FMTs

Although FMTs may sound gross, they save lives and save money. The Centers for Disease Control reports that with the advent of more sensitive testing capabilities and FMTs as treatment and preventative options, fewer people are getting sick from C. difficile.11 FMTs show great promise in treating CDIs, but have not yet been approved by the Food and Drug Administration (FDA), which is having trouble classifying the intervention: Is it a procedure? A drug? Something that doesn’t need regulation? While waiting for the FDA to complete its review and regulate FMTs, physicians and patients shouldn’t be deterred. Both should feel comfortable discussing FMTs as an option for treating the very expensive and painful issue of CDI.

References

1. Carroll KC, Bartlett JG. Biology of Clostridium difficile: implications for epidemiology and diagnosis. Annual Review Microbiology. 2011;65:501–521. https://doi.org/10.1146/annurev-micro-090110-102824

2. Lau CS, Chamberlain RS. Probiotics are effective at preventing Clostridium difficile-associated diarrhea: a systematic review and meta-analysis. International Journal of General Medicine. 2016;9:27-37. doi:10.2147/IJGM.S98280.

3. Heinlen L, Ballard JD. Clostridium difficile Infection. The American journal of the medical sciences. 2010;340(3):247-252. doi:10.1097/MAJ.0b013e3181e939d8.

4. Lessa FC, Mu Y et al. Burden of Clostridium difficile Infection in the United States. The New England Journal of Medicine. 2015; 372:825-834. DOI: 10.1056/NEJMoa1408913

5. Desai K, Gupta SB et al. Epidemiological and economic burden of Clostridium difficile in the United Sates: estimates from a modeling approach. BMC Infectious Disease. 2016; 16:303. https://doi.org/10.1186/s12879-016-1610-3

6. Surawicz CM, Brandt LJ et al. Guidelines for diagnosis, treatment, and prevention of Clostridium difficile infections. The American Journal of Gastroenterology. 2013; 108: 478-498. doi: 10.1038/ajg.2013.4

7. Millan, B., Park, H., Hotte, N., Mathieu, O., Burguiere, P., Tompkins, T. A., … Madsen, K. L. (2016). Fecal Microbial Transplants Reduce Antibiotic-resistant Genes in Patients With Recurrent Clostridium difficile Infection. Clinical Infectious Diseases, 62(12), 1479–1486. https://doi.org/10.1093/cid/ciw185

8. Varier, R. U., Biltaji, E., Smith, K. J., Roberts, M. S., Kyle Jensen, M., LaFleur, J., & Nelson, R. E. (2015). Cost-effectiveness analysis of fecal microbiota transplantation for recurrent Clostridium difficile infection. Infection Control and Hospital Epidemiology, 36(4), 438–444. https://doi.org/10.1017/ice.2014.80

9. Zowall, H., Brewer, C., & Deutsch, A. (2014). Cost-Effectiveness of Fecal Microbiota Transplant in Treating Clostridium Difficile Infection in Canada. Value in Health: The Journal of the International Society for Pharmacoeconomics and Outcomes Research, 17(7), A676. https://doi.org/10.1016/j.jval.2014.08.2512

10. Maida, M., Mcilroy, J., Ianiro, G., & Cammarota, G. (2018). Faecal Microbiota Transplantation as Emerging Treatment in European Countries. In Updates on Clostridium difficile in Europe (pp. 177–195). Springer, Cham. https://doi.org/10.1007/978-3-319-72799-8_11

11. Healthcare-associated Infections. Centers for Disease Control and Prevention. https://www.cdc.gov/hai/surveillance/data-reports/data-summary-assessing-progress.html. Published January 5, 2018. Accessed February 20, 2018.

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