Fecal microbiota transplants are emerging as a novel and effective therapy for antibiotic associated diarrhea. Two new cases in the USA highlight the risks of this therapy unless effectively controlled.
A well-known adverse reaction to antibiotic use is antibiotic associated diarrhea. In most cases, this means that you need to go to the toilet more frequently, have loose stools and feel uneasy in the gut. The symptoms are related to the antibiotic killing not only the bacteria that are targeted with the therapy, but also causing collateral damage to our microbiomes in our gastrointestinal systems, also called dysbiosis. And in most cases, the microbiomes are resilient and more or less recover from the assault after the treatment period ends. But in some cases, and more frequently after use of broad-spectrum antibiotics, the dysbiosis causes a void in the microbiome that is filled by Clostridioides difficile (C. diff) bacteria that start growing and cause a severe, even life-threatening diarrhea.
Fecal microbial transplants
Treating a C. diff infection is not easy. Antibiotic therapy is harsh and the bacteria are becoming increasingly resistant. Learning more about the role of our microbiomes has brought forth the idea that one could remedy the damage caused by the antibiotics and fill the ecological void that C. diff exploits by transplanting a microbiome from a healthy donor. This would be similar to planting new plants in wastelands allowing the ecosystem to recover. Several attempts have been tested to actually perform the transplant, and the most effective approach is a full ecosystem transplant, in effect introducing feces from the donor to the patient via for example oral capsules or colonoscopy. Trials with these methods have shown promise, but the therapy is still investigational.
Two deaths in USA
On June 13, 2019, the FDA issued a safety alert regarding fecal microbiota transplants after two immunocompromised adult patients developed invasive infections by ESBL-producing E. coli. Unfortunately, one of the patients succumbed to the infection. Both patients received the transplant from the same donor, and the donated sample was later seen to contain the infecting bacterium. The donated sample had not been screened for multidrug resistant bacteria prior to use. Unfortunately, the alert does not reveal why these two patients developed the invasive infection – was it the status of their immune system, degree of tissue damage due to the C. diff infection or was the infecting bacterium more virulent, prone to cause disease?
Learning from history?
Unfortunately, infection from donated material is not unheard of in medical history. In the 1970s and -80s, thousands of patients with hemophilia, a blood clotting disorder, were given blood products or transfusions to halt the bleedings, but were instead infected with hepatitis and HIV. It was revealed that some of the blood used was bought from prisons, and that the pooled donated blood was contaminated. Similarly, until the 1980s, children with stunted growth were treated with growth hormones harvested from pituitary glands. Some of the preparations were however contaminated with prions causing Creutzfeldt-Jakob disease.
Future of fecal microbiota transplants – 3 consequences to address
Fecal microbiota transplants have been shown to be effective in the treatment of C. diff infections, and many researchers hope that they could also resolve other issues that have been connected with dysbiosis. The past together with the two new cases should however give pause to think about mitigating the risks that are present. One needs to remember that fecal microbiota transplants are still investigational procedures, there is no “gold standard” for safety precautions or well developed regulatory frameworks. This has three consequences that need to be addressed:
- Transplants should be adequately screened for potentially harmful bacteria. These should include virulence factors and resistance genes. The screening procedures also need to be continuously updated as new resistance genes or virulence factors are identified.
- Patients should be adequately informed about the procedure and the risks involved, especially the most vulnerable patients. The transplants are complex mixtures of bacteria that we still only know a fraction about.
- Appropriate patient groups need to be identified. Are there comorbidities that affect the safety of fecal microbiota transplants?
However effective fecal microbiota transplants turn out to be in treating C. diff infections, efforts should focus on preventing the infection in the first place by observing hygiene recommendations and using antibiotics appropriately.
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