How is a new treatment for C. diff paving the way to potentially treat a host of other conditions and infections?

Academics are investigating more potential uses for faecal microbiota transplant.

Clostridium difficile infection – otherwise known as CDI, C. difficile or C. diff – continues to remain an unpleasant, and potentially severe or even fatal infection that occurs mainly in elderly and other vulnerable patient groups, especially those who have been exposed to antibiotic treatment.

While NHS Trusts in England reported that the number of cases of C. diff has decreased by 77.9% since its peak 2007/8, when 55,495 cases were recorded, in the past year there were still 12,275 cases of C. diff. 

The disease that strikes fear into hospitals

One of the most common causes of hospital acquired infective diarrhoea in the Western world, the disease results from an overgrowth of C. diff bacteria, leading to toxin production in the gut, usually as a result of antibiotic use. 

It can affect the bowel and cause diarrhoea, and is mostly a risk for people who have been treated with antibiotics, are over 65, have a weakened immune system and/or have been in a healthcare setting, such as a hospital or care home, for a long time. It also spreads easily, which is why outbreaks in hospitals can be so dangerous.

A busy hospital with doctors, nurses and staff busy at work in an accident and emergency ward in a British hospital
Patients who stay in hospital for an extended period of time are at significant risk of C. diff infection. Image credit: Alamy.

Why antibiotics don’t always work 

Antibiotics are effective in treating the initial episode of C. diff, but 10-20% of patients don’t respond and the infection then recurs. This recurrence is associated with a dramatic reduction in quality of life and can ultimately lead to death. 

Research carried out by the University of Birmingham’s Professor Peter Hawkey, an internationally recognised researcher who has been working on the problem of C. diff for more than 40 years, was the first to demonstrate the causal link between the use of third generation cephalosporin antibiotics and C. diff; cephalosporin antibiotics are often used for the treatment of septicaemia, pneumonia, meningitis, biliary-tract infections, peritonitis, and urinary-tract infections.

Peter went on to chair the working group set up by the Department of Health and Social Care that produced the action plan that led to the dramatic fall in C. diff cases; ‘Clostridioides difficile infection: how to deal with the problem ’.

“I diagnosed and treated the first UK case of C. diff that were outside the original description of five cases in the Lancet in 1978,” Peter explains. “I maintained a lifelong interest in the condition, and when confronted with two patients in the 1990s as a professor in Leeds, I treated them with faecal microbiota transplant (FMT) very successfully. 

“On coming to Birmingham in 2001 I worked to convince the NHS Trust I was attached to, to deliver FMT. This was, as is usual with a novel and unconventional treatment, a long process. I persuaded the Health Protection Agency, whose laboratory in Birmingham I ran, to support the venture and the first transplants were done in about 2013.”

3D Illustration of a Clostridium Difficile bacteria
3D Illustration of a Clostridium Difficile bacteria. Image credit: Alamy.

It is the patients with recurrent C. diff that are now being successfully treated with FMT: 91% of those with recurrent C. diff recover with FMT compared to only 20-40% with antibiotics. It is also a far cheaper option that treating with antibiotics.

Faeces as a licensed medicine – just like antibiotics

A faecal transplant is prepared from a carefully screened, healthy stool donor and processed in a sterile laboratory setting. It is frozen in a -80°C freezer and can be stored for up to six months.

Under supervision of a gastroenterologist or a microbiologist, it is transplanted into the colon of the patient via a nasogastric tube directly to the stomach or, more rarely, as it is uncomfortable and invasive, via colonoscopy, meaning that the patient can’t taste anything. 

Following the development of FMT as a medicine, granting of the first UK licence for the provision of FMT and awarding of NHS England’s innovation tariff for free supply of FMT to all English Trusts until 31 March 2020, University of Birmingham research has led to the availability of FMT as a treatment option for patients with recurrent C. diff both nationally and internationally (Peter has directed the establishment of the Hong Kong FMT bank at the Chinese University of Hong Kong) through its Microbiome Treatment Centre.

Cure rates that clinicians can only dream of

There are other suppliers of FMT but the Microbiome Treatment Centre is the first licensed facility to comply with Good Manufacturing Practice and is “leading the way and setting the UK standards for FMT production and supply”.

Thanks to the Microbiome Treatment Centre’s pioneering research, FMT has been shown to be highly effective in treating recurrent C. diff cases; multiple clinical trials and a recent meta-analysis produced by the team have demonstrated cure rates of 92% (95% confidence intervals: 89% to 94%). 

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 Peter explains: “Most patients respond to a single infusion of FMT. However, repeated infusions can be given for initial non-responders. What we have found is that FMT for C. diff is effective regardless of the way it’s administered, and this effectiveness doesn’t appear to change if FMT is frozen for up to six months before it’s administered. 

“The result of our research here in Birmingham is that FMT for the treatment of recurrent and refractory CDI is now part of national guidelines, in which I has been closely involved with, and many national local hospital policies too.”

Investigating more potential uses for FMT

There is also increasing evidence that FMT may also be effective in treating active ulcerative colitis (UC). A recent review of the four clinical trials conducted so far revealed that 37% of participants in the FMT group reached clinical remission compared to 18% in the control group. 

The Microbiome Treatment Centre is now collaborating with the largest clinical trial being conducted in the world to date, to determine the effectiveness of FMT for the treatment of active UC: ‘STOP-Colitis’.

The use of FMT is also now being explored for a whole host of other conditions in clinical trials around the world, including hepatic encephalopathy and alcoholic hepatitis, non-alcoholic fatty liver disease, refractory immune checkpoint inhibitor associated colitis and antimicrobial resistance, and more. 

“We’ve prepared over 300 transplants in Birmingham that have been delivered to various hospitals across England,” Peter says. “We have established a good facility for preparing pure faeces from normal people to enable patients who have had their microbiome disrupted by antibiotics or other factors to be replaced with ‘class 1 bacteria’ from the Midlands.

“It’s exciting to find out what other diseases this extraordinary treatment can be used for.”

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