Correcting the altered gut microbiome is an important goal in Clostridioides difficile management. Due to high recurrent infections and significant failure rates for mainstay antibiotic therapy, microbiota-based therapeutics such as faecal microbiota transplantation are under investigation and pharmacists should be prepared to support their use, says Tiene Bauters PharmD PhD.
A highly complex community of microorganisms colonises the gastrointestinal (GI) tract, collectively called the ‘gut flora’ or ‘gut microbiome’. These microorganisms play an important role in protecting against pathogens, aiding digestion, synthesising essential vitamins and influencing the immune system’s development, maturation and regulation.
Alterations in the healthy microbiota composition can result in the selective removal of bacteria that serve as barriers to pathogen colonisation and persistence. These alterations in the gut barrier may also lead to mucosal immune effects, allowing certain ‘bad’ pathogens, such as Clostridioides difficile (C. difficile), to colonise the gut successfully.
C. difficile is one of the primary nosocomial pathogens and can cause diarrhoea, abdominal pain and fever, and, in severe cases, organ failure or even death.
This infection is often a consequence of antibiotic therapy. In cases of antibiotic-associated infection, standard antibiotic therapy for the infection has a high failure rate. Furthermore, up to 20% of those affected may experience recurrences.
Addressing the imbalance
Faecal microbiota transplantation (FMT) is a relatively new procedure, and practices vary between institutions. Although there is no universally accepted definition of FMT, it generally refers to the transfer of biological material containing faecal microorganisms from screened, healthy human donors to the GI tracts of patients. In some cases, autologous use may also occur.
FMT aims to modify the large bowel microbiota, which, in turn, re-establishes normal bacterial composition and mechanisms.
Emerging evidence suggests that FMT might be a therapeutic option for a variety of medical conditions, such as irritable bowel syndrome, metabolic syndrome, Crohn’s disease and even depression and autism. However, the most robust evidence for FMT use is in treating recurrent C. difficile infection.
How is FMT done?
FMT products fall into two categories: extemporaneous or manufactured preparations.
FMT can be administered ‘fresh’ or via freeze-thawed stool preparations. Generally, stool for FMT is suspended in normal saline before administration, homogenised to a liquid consistency and filtered to remove particulates.
Delivery of FMT via oral capsules is the most convenient, feasible and non-invasive method. Lower GI tract procedures such as retention enema and colonoscopy, or upper GI procedures requiring the placement and radiologic confirmation of a nasojejunal or nasoduodenal tube are also used, although the latter carries a risk of vomiting.
The choice of delivery route depends on patient preference, accessible resources, cost and available expertise. It can be performed in an outpatient setting, although some patients may require hospital admission.
FMT is usually well tolerated, with mild-to-moderate side effects that are generally self-limiting. Potential risks include procedural complications such as GI bleeding after nasogastric tube insertion and colon perforation during colonoscopy. Despite careful donor selection, the risk of infectious agent transmission from contaminated donor stool does remain.
FMT from clinical trials to the market
Since the first randomised clinical trial in 2013 demonstrated that FMT was superior to antibiotics for recurrent C. difficile infection, its use has surged as a routine, investigational therapy in Europe.
Baunwall et al published the results of a Europe-wide survey of clinical use and estimated that approximately 2,000 hospital-based procedures were performed in 2019. FMT centres operate widely across Europe, but the survey suggested the need to increase awareness of the procedure, address the significant unmet need for treating recurrent C. difficile infection and harmonise clinical practices.
The EU-Innovation Network Horizon Scanning Report on FMT was published in June 2022. It describes the current use of FMT, highlights emerging trends and explores regulatory challenges and opportunities.
In 2023, the US Food and Drug Administration approved Vowst as the first orally administered faecal microbiota product indicated for the prevention of recurrent C. difficile infection in adults following antibacterial treatment.
It is available as a bacterial spore suspension in capsule form, manufactured from human faecal matter sourced from qualified donors. The recommended dosage is four capsules orally once daily for three consecutive days. The most common adverse reactions are abdominal distension, fatigue, constipation, chills and diarrhoea.
The FDA has also approved the commercial faecal microbiota rectal suspension Rebyota to prevent C. difficile infection recurrence in patients with at least two prior episodes. It is administered as a one-time dose. The most commonly reported adverse reactions following a single dose were abdominal pain, diarrhoea, abdominal distension, flatulence and nausea.
FMT has proven effective for C. difficile infection treatment, but continued research is needed to assess the benefits of different administration routes, alternative indications and long-term side effects. Randomised, controlled clinical trials will be beneficial in determining the impact of FMT among larger, more diverse populations. Numerous clinical trials are ongoing to evaluate FMT for various medical conditions.
Conclusion
The introduction of FMT reflects the growing interest and advancements in microbiome science. This development presents new opportunities and highlights the importance of pharmacists understanding the role of the microbiome in human health and disease.
Moreover, as FMT products become licensed, pharmacists should be prepared to support their use, including identifying and managing eligible patients, assisting in procurement, facilitating communication among healthcare team members and monitoring for side effects and drug-related risks.
Author
Tiene Bauters PharmD PhD
Pharmacy Department, Ghent University Hospital, Ghent, Belgium
