C. difficile

C. difficile is a hospital-acquired
infection that causes severe diarrhea
and can be life threatening, particularly
for the elderly. Few currently available
antibiotics are effective against C.
difficile infection and drug resistance is
a growing threat.




DIFICID BY OPTIMER IS APPROVED
BY FDA  AGAINST C. DIFFICILE
In May 2011 the FDA has approved a
new medicine, marketed under the
trade name Dificid by Optimer
Pharmaceuticals Inc., for Clostridium
difficile.

Clostridium difficile (CDAD) is a
bacterial disease  which can impact
both children and adults.
Commonly, the bacteria  is picked up  
in the hospital.

If children and / or adults contract the
bacteria, they develop a stomach bug
which can lead to diarrhea, as well as
colitis.

The bacteria rests in the stomach area
of its victims and can be a very
unpleasant experience to say the least.

As of right now, the common antibiotic
to treat CDAD was a drug known as
vancomycin.

That may change though as two trial
showed this new drug Dificid, to be an
improvement over vancomycin.

Research showed that patients treated
with DIFICID suffered recurrences in
15 percent of cases, compared to 25
percent for vancomycin. That's
important, because if a patient has one
recurrence, he or she has a 50
percent chance of getting a c-diff
infection a third time, and successive
cases require longer treatment.



FECAL BACTERIOTHERAPY TO
CURE  PATIENTS WITH C DIFFICILE
The Clostridium difficile bug, typically
caught by patients in hospitals and
nursing homes, can be hard to treat
with antibiotics.

Dr. Alexander Khoruts, a
gastroenterologist at the University
Minnesota, uses bacteriotherapy to  
cure a patient suffering from a gut
infection.
He took on a patient suffering from a
vicious gut infection of Clostridium
difficile. She was crippled by constant
diarrhea, which had left her in a
wheelchair wearing diapers. Dr.
Khoruts treated her with an assortment
of antibiotics, but nothing could stop
the bacteria.
Dr. Khoruts decided his patient
needed a transplant. But he didn’t give
her a piece of someone else’s
intestines, or a stomach, or any other
organ. Instead, he gave her some of
her husband’s bacteria.

Dr. Khoruts mixed a small sample of
her husband’s stool with saline solution
and delivered it into her colon. Writing
in the Journal of Clinical
Gastroenterology, Dr. Khoruts and his
colleagues reported that her diarrhea
vanished in a day. Her Clostridium
difficile infection disappeared as well
and has not returned since.
The procedure — known as
bacteriotherapy or fecal
transplantation — had been carried
out a few times over the past few
decades. But Dr. Khoruts and his
colleagues were able to do something
previous doctors could not: they took a
genetic survey of the bacteria in her
intestines before and after the
transplant.

Clostridium difficile is a spore-forming
bacterium which is probably most
commonly 'caught' through the mouth
often in hospitals, especially after the
use of antibiotics. It can result in
syndromes of varying severity
including transient diarrhea, a carrier
status, a mild colitis-like illness,
pseudomembranous colitis, and even
toxic megacolon with possible mortality.

Most affected patients can respond to
medical therapy including
discontinuation of the responsible
antibiotic. It is not the antibiotic that
causes the infection but rather the
antibiotic use weakens the defense of
the bowel bacteria so permitting C.
difficile to implant in the bowel.  
However, despite a seemingly
successful initial treatment around
25% or more patients may have a
recurrence of diarrhea following
withdrawal of the antibiotics. This is
thought to occur because the normal
flora may not at this time, possess the
power to eradicate the persisting
Clostridial spores. In many patients the
C. difficile spores remain and a
chronic, relapsing disease can
continue. Treatment of this recurrent
C. difficile diarrhea can be particularly
difficult, mainly because we do not
have the tools to kill spores.

If all medical therapies fail, re-
colonisation of the colon using human
fecal origin probiotics has been used
and reported to be successful in
eradicating spores.

At Probiotic Therapy Research Centre,
Sidney, Australia they focus
particularly on those cases where
other therapies have failed. In such
patients they may initially use a
combination therapy with vancomycin,
rifampicin and metronidazole together
combined with Lactobacillus GG. If all
pharmacological therapies fail, human
probiotic infusion (HPI) is used to
terminate the C. difficile infection since
human fecal flora bacteria appear to
have the capability to permanently
eradicate C. difficile spores - a
treatment not able to be matched by
any other currently known therapy.
Using HPI, the cure rate approaches
90-95%.

There's little doubt this treatment has
an image problem. Feces, including
important bowel flora, is transferred
from a volunteer donor -- screened to
limit possible other infections -- into the
colon of the infected patient. The
treatment can be administered by a
colonoscope or an enema, or by the
mouth or the nose.

The donor feces is filtered to remove
some larger particles and then "simply
goes through a blender," says
Khoruts, with a saline solution to
liquefy it before it is administered.





NEW ANTIBIOTIC IN PHASE 1 TRIAL
AGAINST C DIFFICILE
In November 2011 Novacta Biosystems
(UK) has commenced dosing of the
first healthy volunteers in a phase I
clinical trial of a new antibiotic to treat
the hospital superbug Clostridium
difficile.

Laboratory studies have shown that
the new compound, NVB302, is
effective against all strains of
Clostridium difficile tested, without
adversely affecting the healthy
bacteria that are normally found in the
gut.

Developed with support from a
Wellcome Trust Strategic Translation
Award (UK), NVB302 is now being
tested in a first-in-man trial to
determine the safety and tolerability of
the compound in healthy volunteers.

NVB302 is a member of a class of
antibiotics known as the type B
lantibiotics, a naturally occurring class
of antibiotic compounds found in many
bacteria. Lantibiotics have shown great
potential to treat superbug infections
such as C. difficile and MRSA;
however, conventional medicinal
chemistry has not been able to
optimise the structure of the naturally
occurring compounds into a form with
the potential to treat human disease.

Novacta's proprietary technologies
have allowed the structural
manipulation and optimisation of the
lantibiotics' antibiotic activity, to unlock
the potential of this novel and
underexploited class of compounds.