One of the unfortunate side effects of taking antibiotics to clear bacterial infection is its effect on the body’s microbiome. Antibiotics are generally nonselective in their targets; being put on a regimen of antibiotics can kill off an infection, but it will likely also cause harm to the beneficial bacteria of the patient (Dethlefsen et al., 2008). This creates openings in the niche environments of the microbiome, freeing up space that can be used for colonization in a subsequent infection. One of the organisms that takes advantage of this opening is Clostridioides difficile, a bacterium heavily associated with diarrheal disease that in severe cases can develop into colitis. C. diff infections (CDIs) are almost always the result of an antibiotic treatment for some other infection. Seeing how this is the case, it is easy to picture the problem that many clinicians face when trying to treat a CDI. How do you treat a bacterial infection that was caused by antibiotic treatment? It seems counterintuitive to give the patient more antibiotics, but that actually has been the most common practice in the last few decades. Understandably, due to the nature of C. diff infections, up to 35% of treated cases relapse within 8 weeks post treatment (Singha et al., 2019). This shows the critical need for new or more effective treatments for CDI.
In 1958, Dr. Eiseman of the United States was the first physician to show high success rates in treating colitis with what would later be known as Fecal Microbiota Transplant (FMT). This essentially involved isolating the microbiota from a healthy individual’s stool, and using it to recolonize the microbiomes of infected individuals. The good bacteria from the donor would outcompete the pathogenic bacteria in the patient’s system, reclaiming the digestive tract. However, it took 55 years before randomized controlled trials of FMT were conducted. In fact, the initial numbers showed a 90% cure rate, leading researchers to switch all patients over from antibiotic treatment to FMT before the end of the investigation (Van Nood et al., 2013) Researchers of this study, Jorup-Rönström et al., set out to conduct a similar FMT experiment treating 32 patients with CDI. 22 out of 32 patients were cured outright, with an additional 4 patients experiencing significantly less severity of their symptoms. This translates to over an 81% success rate in the study. With results like these, why did it take so long before adopting new strategies to combat CDI?
Dr. Eiseman completed his preliminary study in 1958, during a time of great development in modern medicine. Antibiotics had just come from left field as a miracle cure in the previous decade, while the next several years were saturated with new antibiotic discovery and implementation, putting FMT on the backburner until now. Overuse of antibiotics during these years contributed towards the growing problem of multi-drug resistant organisms (Llor and Bjerrum, 2014). In fact, with C. diff in particular, the CDC has classified it as an “Urgent Threat”, its highest level classification of dangerous organisms, due to its drug resistance. Additionally, a “fecal transplant” has a fairly bad connotation and could, understandably, deter potential patients from trying the treatment. Regardless, FMT is gaining ground and is already the go-to treatment for patients with recurrent CDI. Hopefully, we will be able to see it gain further popularity in medical institutions during this era where multi-drug resistance is becoming more common.
Link to this article: https://doi.org/10.3109/00365521.2012.672587 Fecal transplant against relapsing Clostridium difficile-associated diarrhea in 32 patients
References
Dethlefsen, L. et al. (2008) ‘The Pervasive Effects of an Antibiotic on the Human Gut Microbiota, as Revealed by Deep 16S rRNA Sequencing’, PLoS Biology, 6(11). doi: 10.1371/journal.pgen.1000255.
Llor, C. and Bjerrum, L. (2014) ‘Antimicrobial resistance: Risk associated with antibiotic overuse and initiatives to reduce the problem’, Therapeutic Advances in Drug Safety, 5(6), pp. 229–241. doi: 10.1177/2042098614554919.
Van Nood, E. et al. (2013) ‘Duodenal infusion of donor feces for recurrent clostridium difficile’, New England Journal of Medicine, 368(5), pp. 407–415. doi: 10.1056/NEJMoa1205037.
Singha, T. et al. (2019) ‘Updates in Treatment of Recurrent Clostridium difficile Infection’, Journal of Clinical Medicine Research, 11(7), pp. 465–471. doi: 10.1001/jama.2018.18993.
