Faecal transplantation is a promising option for C. difficile
infections, yet it’s not a mainstream treatment. Kate Woods
investigates.
ON ITS own, a case of severe or relapsing Clostridium difficile infection (CDI) is a distressing problem.
The
fever, loss of appetite, nausea, abdominal pain and tenderness
resulting from severe diarrhoea and associated intestinal inflammation
are debilitating for the patient.
That’s why when Sydney
gastroenterologist Professor Thomas Borody met Sarah,* a 14-year-old
with Crohn’s disease who had just been diagnosed with C. difficile, he
knew she was suffering.
“Sarah was experiencing the severe
abdominal pain, she was vomiting daily and she was visiting the toilet
15–20 times a day,” Professor Borody says.
With antibiotic agents
failing to rid her of the infection, Professor Borody suggested they
try faecal microbiota transplantation (FMT).
While the procedure
may seem unpleasant to some patients – it involves the transfer of
bacterial flora from the stool of a healthy donor into the person with
the infection – she gave permission straight away.
“Her parents were a little reticent; it took them a lot longer to give the permission.
But they finally agreed and we went ahead,” says the director of the Centre for Digestive Diseases in Sydney.
When
the stool transplant nurse called several days after the
transplantation to ask how she was feeling, Sarah replied: “Amazing! I
have been just amazing.
“‘The only thing now is my legs – they really hurt because I have been dancing all day.”
In
such a short period of time, Sarah had gone from visiting the toilet
15–20 times a day, to passing just one formed stool a day.
“This
little girl had suffered so much,” Professor Borody says. “Her Crohn’s
disease was pretty bad and then she had the C. difficile on top… These
results changed her whole outlook – it was just wonderful to see.”
Despite encouraging results from Professor Borody’s group, FMT is far from standard practice in Australia.
FMT, also known as faecal bacteriotherapy, is a controversial treatment.
It involves taking bowel flora from the stool of a healthy donor and homogenising it in sterile saline.
The
slurry containing the living protective bacteria is then infused into
the bowel of the patient through colonoscope, enema or nasojejunal tube.
1
Professor Borody says the treatment is almost exclusively used to reverse severe or relapsing C. difficile.
“There
is nothing that comes close as far as effectiveness. You need only a
single infusion and you get virtually a 100% cure rate,” he says.
Furthermore, he says it is extremely safe.
Donors
are screened for relevant communicable diseases and assessed for risk
of infectious disease, gastrointestinal comorbidities and factors that
can affect the composition of the intestinal microbiota.
“You would have thought that if you are using poo, things would be dangerous. The reality is diametrically opposite.
“You
might have a bottom that is sore if a tube is inserted roughly, but
there is not one instance of a complication caused by the bug flora
itself.”
Professor Borody says 50% of the donor stools used in
his clinic come from the relatives of patients and 50% from the clinic’s
donor bank.
“Donors are tested every two weeks – blood and
stool – and they need to have symptoms of normality; one formed sausage
per day.”
While FMT is currently used for severe or relapsing C.
difficile only, research has shown it may also be effective for
improving other conditions such as ulcerative colitis and constipation.
There
has also been a spate of recent publications suggesting FMT can change
patients’ insulin sensitivity levels, and that it may be beneficial in
the treatment of obesity, Professor Borody says.
“Research into
this area is just burgeoning. I’d say that in the next 20–30 years, we
are going to learn far, far more about the importance of the stool
itself.”
Support for this procedure hasn’t been great in
Australia; Professor Borody’s team is the only group who will carry out
the transplant.
In the US however, there are about 200 centres performing FMT.
In
fact, growing popularity there has led to the development of an
inter-specialty position statement aimed at helping drive FMT towards US
Medicare reimbursement by 2013.
In the statement, experts admit
additional data is needed to assess the efficacy of FMT, but say there
is encouraging data to date and pending data to show it is an effective
treatment option.
2
“Although vancomycin is the only drug
that is approved by the FDA to treat CDI, it is clearly insufficient
for many patients with recurrent disease. This predicament has forced a
number of alternative therapies to be tried and to be developed,” they
say.
“However, none has yet proved to be highly effective, safe and
inexpensive. In contrast, with a cumulative reported cure rate of >
90%, negligible rate of significant adverse effects, and response of
hours to days, FMT appears to fit these criteria.
“Furthermore,
FMT is the only therapy that restores the phylogenetic richness of the
recipient’s intestinal microbiota without prolonging the perturbation of
the normal microbiotic composition.”
If approved, Professor
Borody says the procedure will most likely fall into the same Medicare
category as bone marrow transplants and will be subject to the same
ethical considerations as a blood transfusion, a sperm donation or an
egg donation.
So why hasn’t the procedure taken off in Australia?
According
to Associate Professor Terry Bolin from the Gut Foundation, a big part
of the reason is the offensiveness of the procedure to patients.
“While
it is used extensively in the United States, I think in Australia most
people have significant reservations about the procedure because it
involves putting someone else’s faeces into your colon,” he explains.
“I am not going to get into it and I know many others who are not getting into it.
Instead I think it will remain the tool of some very specialised people.”
Associate
Professor Bernie Hudson, an infectious diseases physician at Sydney’s
Royal North Shore Hospital, agrees negative patient attitude towards FMT
may play a big part, but suggests the other reason may be the procedure
is not standardised.
“Obviously aesthetically it is not a
particularly nice procedure to do, but I think a lot of people also feel
that there needs to be standardisation before they will use it.”
He says he has referred a number of patients with C. difficile to Professor Borody when other therapies have failed.
“And
in those couple of cases, it has worked absolutely perfectly. It has
resulted in a complete cure without any side effects,” Professor Hudson
says. “In fact these patients experienced more side effects from the
treatments that only resulted in temporary relief from symptoms.”
He
says with treatment options for relapsing C. difficile limited, he
suggests more doctors may need to turn to FMT in the future.
“The
current treatments just don’t seem to work. People might get partial
relief but then relapse quite quickly after stopping them. Different
treatments may need to be seriously considered in the future.”
Indications for FMT in C. difficile infections (CDI)2
1. Recurrent or relapsing C. difficile infection.
a.
At least three episodes of mild-to-moderate CDI and a failure of a 6-
to 8-week taper with vancomycin with or without an alternative
antibiotic.
b. At least two episodes of severe CDI resulting in hospitalisation and associated with significant morbidity.
2. Moderate CDI not responding to standard therapy (vancomycin) for at least a week.
3. Severe (perhaps even fulminant C. difficile colitis) with no response to standard therapy after 48 hours.
In
all cases, primary consideration must be given to the severity and pace
of the patient’s CDI when deciding whether early use of FMT is
appropriate to prevent further clinical deterioration.
References
1. Borody T. Infection with Clostridium difficile.
www.cdd.com.au/pages/disease_info/clostridium_difficle.html Last accessed 5th September.
2.
Bakken JS et al. Treating Clostridium difficile Infection with fecal
microbiota transplantation. Clin Gastroenterol Hepatol 2011, published
online 23 August
*Name has been changed to protect the patient’s identity.
