CC
Nite at the Lab. >> Welcome everyone to Wednesday
I work here at the UW-Madison Biotechnology Center.
I also work for UW-Extension, Cooperative Extension.
On behalf of those folks and our
Wisconsin Public Television, the other sponsors, including
the Science Alliance, thanks for Wisconsin Alumni Association and
Lab. coming to Wednesday Nite at the
night, 50 times a year. Tonight it's my pleasure to be
able to introduce to you
She studied medicine at the Aga Khan University Medical College
in Karachi, Pakistan before coming to Madison in 1997.
As a resident in internal medicine here at the UW Hospital
and Clinics.
Health in 2002 and took a Sfellowship in Women's Health
from 2002 to 2005.
professor in the section of In 2infectious diseases, theant
Department of Medicine here at
Since 2009 she has also served the UW Hospital and Clinics.
infectious diseases at the as a staff physician in
Veterans Hospital here in William S. Madison.n Memorial
She is board certified in infectious diseases and internal
medicine. Tonight she gets to talk to us
about sleuthing, reducing and resolving Clostridium Difficile
infections. Please join me in welcoming
Dr. Safdar to Wednesday Nite at the Lab.
[applause]
Good evening everyone. >> Thank you, Tom.
here. Today we'll be talking about
Clostridium Difficile infections.
I think it's always instructive to go back and figure out how it
all began.
C.Dif , which is The way it all began with
something that, when I was a resident ten years
ago, we used to see a little bit
Only enough to say that it's a of.
that's readily treatable and nuisance but it's something
about. nothing that we need to worry
now, where most of our clinics To the situation that we have
Clostridium Difficile infection. It's an increasingly are filledvirulentople with
infection, and increasingly difficult to treat.
Things have clearly changed.
by Hall and O'Toole, and they all felt that it was a commensal
organism of the GI tract. Something that was there
normally and was not pathogenic and did not cause any symptoms
to be of any concern. It was initially described in
new-born infants. Interestingly, new-born infants,
up to probably age, I would say,
although they can harbor two years, children still,
disease from C.Difficile clinical
That's not to say that they can't pass it on to their moms
and dads, and other people they come in contact with.
But they, themselves, do not get
The causes of that is unclear. sick from it.
not much happened. After it was described in 1936,
science happened, but nothing related to C.Dif A lot onecessarily.nces in
Until the 1970s when the
recognized that individuals who where being given an antibiotice
called Clindamycin subsequently developed inflammation of the
intestine.
Clindamycin-Associated Colitis, but it wasn't clear at all that
it was infectious.
then converged to define what Clindamycin-associated colitis
was.
when John Bartlett from Johns Hopkins discovered that if you
gave hamsters Clindamycin and then gave then Clostridium it
produced the exact same syndrome
colitis did. as Clindamycin-associated
Clostridium Difficile was toxin-producing organism that,
when ingested by individuals in the right setting, gave them a
severe colitis, or inflammation of the intestine.
It's a strictly antirobe, spore-producing organism that is
very difficult to grow. That's how it got it's name,
Clostridium Difficile.
in the media to grow, and has a characteristic odor which people
say is like elephant manure.
like, I don't know what kind of If yocompany you keep.smells
[laughter]
It's a barnyard odor. I meaThat's helps.cult.
Some people would be familiar with that.
Here's what it looks like.
You know, over the last 20-30 years, once it was described,
people recognized that you could
called Metronidazole. So paradoxically, a syndrome
that's caused by an antibiotic
antiinfective. can also be treated with an
were not terribly bad. People did find the outcomes
least they weren't dying of it. But in the last ten years theret
was a slew of investigations
medical journals indicating that that all were published in major
of C.Difficile. tThis is one of probably fiven
or six. It's not a problem that is
localized just to this country, or even to this continent,
but is a global issue that
grips with. people arThere was oneto come to
multi-institutional outbreak of C.Difficile in this country.
This is the one from Canada, but
country, that was associated there's similar ones in this
high mortality. wiIt was pretty clear thatry
super-bug back. So we had to find a way to
combat it.
do, is you have a support group. Of course, the first thing you
C.Difficile support group. There is a wrist band So there is a bone fide
can order. that you
other than that it's not You do have to pay shipping, but
Why is it that C.Dif has expensive.
In order to get into that it's changed over the last few years.
population that it attacks. Here you see on this slide, from
1991 all the way to the end of
C.Difficile infection which have been stratified by 2003, you'll nage.e the rates of
The highest rates and the most
that the scale had to be astronomical rise, enough so
the age of 65. truncated, is in people over
people, but rapidly approaching Wthat myself, I now callr
middle-aged.
high risk. People over the age of 65 are at
If you look at national We'estimates of US short-staybe.
hospitals and their diagnoses,
infrequent that C.Difficile would be listed as either a
primary diagnosis or as any diagnosis.
But in the last five, ten years are so, you see that orange line
here is any diagnosis is rapidly
Some people question, is this really an increase in incidence
or is this more that we are now diagnosing it better and
detecting it sooner and more
It's probably a combination of accurately.
Now this trend hasn't really both.
years and our diagnostic methods changed over the last several
number of years. have been pretty good for a
rise in incidence that is So we suspehappening.'s really a
The is a number of definitions
There are national guidelines for how to define
C.Difficile infection.
report C.Difficile It has importance because now we
innational rates of thesech kinfections.of
In order to attribute to an institution, and therefore risk
being labeled as an institution that has C.Difficile
in it, you have to make sure
it. thThe way we usually say is, ang
case of CDI or C.Difficile
i diarrhea or toxic megacolan which is defined as dilation of
the intestine, without any other
test specifically for C.Difficile in the stool, known etiologeither you have to
by means of a toxic assay or a
Or PMC, which is PCR.
pseudomembranous colitis , which
is a specific type of colitis,
histopathilogical examination. has to be found on
the community or whether it was Hosomething that was acquiredrom
inside the institution and
In order to call it healthcare hospitalized patients?
has to develop it more than 48 facility-onset the individual
admitted to the hospital. The premise being that they
shouldn't be incubating it at the time that they come, but
they were in the hospital,
must have been acquired from then they got it, therefore it
hospital environment. soYou can also have a syndromehe
called community-onset, but still healthcare facility-
associated. This was recognized when people
discovered that when hospital stays were getting shorter,
individuals while they were in-house, or in the institution,
felt fine, but as soon as they
C.Difficile. went home they got
that. So even though it occurred inh
the community, it is still
hospitalization that they had. clearly linked to the recent
30 days after last discharge The symptom onset is less than
suggesting that that institution from a healthcare facility,
the individuals C stil .Difficile. True-- giving
Yes.
True community associated CDI is very rare.]
It's rising in incidence as well, as are most other things
in the community, and spilling
But in general, most cases of C.Dif that you will see over into the hospital setting.
have some connection or the other to a healthcare facility,
or a recent hospitalization.
episode of CDI will recur. 40% of people that have one
Recurrent C.Dif is usually
defined within the eight-week time-frame of the previous
episode.
number of CDI cases per month Gper 10,000 patient days.s
This is the rate that we follow and gets reported to the CDC,
which then generates national and state-specific rates to send
back to us. Now, what are the factors that
people think have contributed to
infection? resurgence of C.Difficile
the strain seems to be something First of all, the virulence of
There are these epidemic strains that's new.
that have now become more which werenimportant.ed before,
That's clearly one factor.
of resistance to antimicrobials. disease
prevalent are resistant to Most of the strains that are now
Hence, when people get Clindamycin.
everything else but C.Difficile over grows Clinand thereby causesoff
disease.
immunocompromised population, Thwhich is the population ater
highest risk for getting
And on top of it all, is what C.some people think has also
contributed, which is the alcohol-based handrubs which are
commonly used for hand hygiene. Alcohol-based handrubs are not
sporicidal and have no impact on
The reason there is a question C.Difficile.
studies that have been done, did mark there, is because a few
you use an alcohol hand gel you not are more likely to get is
C.Difficile . But because it doesn't work for
it, I think it makes biologic plausibility and makes sense to
think that, if you're using your
hand gel, that C.Dif hand washing agent as an alcohol
Those are all factors that rates may rise.
This is just the tip of the people thiniceberg.ontributed.
The individual that you see who has clinical disease represents
a fraction of everybody that is colonized or has been exposed
to C.Difficile, but for
one reason or another, did not get
clinically sick from it.
Pseudomembraneus colitis , or PMC
as it's called, if you see an individual with that, 95% to
100% of the time, that's related
You will be able to see a tpositive toxin assay that will
reflect that. It only accounts for about a
quarter of all antibiotic-
A lot of people that we give associated diarrhea.
diarrhea, but when you test for C.Dif you'll find that aget
quarter of them with have a positive test.
The remainder, we don't really
It's thought to be a combination know what causes it.
antibiotic flora in the intestine, but nothing specific
that you can specifically treat and get rid of.
Hospitalized patients, about 20%
C.Difficile and will of them will be exposed to
caunspecified period of time.or Very few healthy adults will
carry C.Difficile infection. Many of us, if we do,
nontoxigenic, or the non-toxin it will be
producing C.Difficile, which is
non-pathogenic and is not of
But a few of us will carry toxic any concern.
And look at how many healthy Clostridium Difficile .
in their intestine. More than 50%- 65% of them.
What are the risk factors for CDI?
Besides the age, antimicrobial
universally reported in people exposure is something that is
Some individuals after GI surgery, even independent of
antiinfective use will get it.
ICU or hospitalized patients Tube feeding, as is common in
common risk factor. And in recent years this isa
something that surprised
Proton pump inhibitors, or individuals when it came out.
used very widely in this country omeprazole or the like, that are
H2 blockers, such as Zantac or and worldwide.
factors for causing ranC.Difficile .also risk
Not just causing it, but also exacerbating it in people who
have already gotten the infection.
Yeah. >> Do they know whether the
incidence of older people using those proton pump inhibitors and
the H2 blockers might be the
The age, I think, is an issue reasfor a number of factors.ue?
We'll go into that in a little
But they did look at case controlled studies where they
looked at a variety of age
age, it seemed that if you were taking a proton pump inhibitor
you were at higher risk of
Not just of C.Dif, but C.Dif.
also of pneumonia, interestingly.
Among the illnesses, and this also is something that may be
relevant to age.
comorbidities and other As withillnesses.s other
Organ transplantation and chronic kidney disease or renal
failure are all factors that
of CDI. Many cancer agents have activity
beyond their cancer fighting
properties, and so cancer potenchemotheropic agentbiotic
independently also have a high
So something that we keep in infection.
If you were trying to get C .Difficile infection, how
would go about it?
get hospitalized for a prolonged The easiest way to do it is to
You can see that in this slide, this is several years ago but,
some things, they don't change. If you look at the length of
hospital stay, at four weeks, about 50% of people will
have acquired C.Difficile.
environment. Probably from the hospital
sure that your length of stay is To avoid it, you have to make
Not all antibiotic agents are lessthe same.eek.
Some frequently induce
infrequently induce it. So for people that have had one
episode of CDI, we always take
ever need antiinfectives, for say a urinary tract infection or
pneumonia, we try and chose an
rare or low risk of inducing C.Difficile .t has a
But you'll notice that even agents that are used for
treatment of C.Difficile
So in that last column on the right, under the rare induction,
Medronidazole and Vancomycin are
frequently used for treatment of both antibiotics agents
have also been shown to cause reit.ts
The ones that cause C.Difficile frequently,
familiar to people in the maaudience here.e
The biggest one that is used
quinolones, ciprofloxacin, very frequently now is
Very commonly used for moxifloxacin and the like.
infections, for urinary tract pneumoninfections.t tissue
Those are ones that used to be
inducers, but actually it's pretty clear now that they are
frequent inducers.
associated with the resurgence In fact, ciprofloxacin use was
been described world-wide. of the epidemic strain that's
you get exposed to The clinical spectrum, should
C.Difficile, one of these things can happen.
They don't have to be in order. You can go from having no
symptoms to having toxic
illness. megacolon, or very severe
spectrum is that you can carry But generally speaking, the
need be any the wiser. it in your intestine and nobody
associated diarrhea. You can have antibiotic-
associated colitis with pseudomembranes, which basically
means, severe colitis but not very severe colitis.
Then you can have pseudmembranous colitis, which
is the very severe form.
which is something that requires Then you can fulminant colitis,
correction. suHow do people acquirend
C.Difficile?
and then after that, you get An individual gets hospitalized
whatever reason, either there's ea urinary tract infection or
pneumonia or something that requires antibiotics for
treatment.
your normal intestine, which is perfectly capable of posing an
immense amount of resistance to pathogens, no longer has quite
the degree of colonization
killed off a lot of the good resistance, because you've
protect you. bacteria that would otherwise
invasion of a pathogen, and with So the milieu is then set for
the hospital environment, if you everywhere in
shop in the intestine, and then one of two things will happen.
You will either get sick, you will get C.Difficile
you will have asymtomatic C.Difficile colonization colitis, or
intestine, but you will not get isick.r
What is it that determines which
It happens in a matter of days. ofSo in less than five or sixen?
days, these events happen.
verses diarrhea is very Whatinteresting to see.ation
This was a med-analysis that
studies. looked at several perspective
colonized with They found that if you were
C.Diget active disease. But if you were not colonized
with C.Difficile, almost
4% There is something aboutve disease.
protects you from getting succeclinical disease.n that
Which is good from the viewpoint
the viewpoint of spread in the of individual patient, but from
much. hoEven if you have it in yourean
intestine, if you're well,
spread it to other people. that's great, but you can still
the IgG antibody against toxin A It is the relationship between
determines whether one will get sick or not.
We now that with aging come immunosenescence and the ability
to have a deficient antibody
That's what most people think is response to pathogens.
mount the antibody response to why older adults are unable to
Renal failure and organ transplantation only compound
that factor.
published now almost 12 years This was a Nago.ngland study
They looked at the incidences of
disease with C.Difficile. bOn the X-axis you have thee
levels of IgG antibody against
You can see that the higher the level of IgG, the lesser the
incidence of both mild disease
If you don't have the capacity and severe disease.
severe disease with C.Difficile. That's led to make antibodies, you get
advances as far as treatment to a number of
What is the mechanism of options for C.Difficile .
Well, they cause a lot of disruption of the tight junction
of the cells. There's intense fluid
accumulation. The cells become very permeable.
There's intense neutriphilic
A and the toxin B, which is the infiltwo major toxins that toxin
C.Difficile produces. Eventually the individual gets
clinical disease which looks
This is Pseudomembranous like this.
The yellow things that you see specimen.
excavated would just go to the are all neutriphiled and --
Not something you want to have surface of the intestine.
Histropathologically speaking, at any time.
It's called the volcano, or the mushroom effect, which is really
this intense migration of white cells to the area of
inflammation. It's not specific for
C.Difficile . It can look like this in other
pathogens that cause intestinal problems, but more associated
with this than anything else. As if that were not enough, in
recent years there's been an
and toxin B that has been described with additional toxin, beyond toxin A
This is called binary toxin, and C.Difficile .
unclear at this point. the mechanism of what it does is
regulatory genes that regulate But what happens is the
get deleted, and so there is no control mechanism over how muchB
of toxin A and B is produced. What people have found is that
with this new strain called the B-1 or the nap-1 strain of
C.Difficile, it produces
23 fold of the amount of toxin B and
produce. that a non-epidemic strain would
the largest known to man, so And colstridial toxin are among
resistance to antibiotics, such there'as what I mentioned,ty for
Ciprofloxacin for example.
sepsis, of leukemoid reactions, meaning a very high white count
when you get infection, the need
So what is a way to diagnose for a colectomy, and death.
There's a number of ways that C.Done can do it.
There's clinical clues. There's laboratory tests, x-ray
imagining and then endoscopic procedures.
Many nurses in the hospital will
patient has C.Difficile. swear that they can tell if a
that looked at whether an individual's sense of smell can
actually predict if diarrhea is caused by C.Difficile
verses something else.
looked at nursing personnel Thwhere they had stools withy
C.Difficile, and they found that they could detect it.
Sensitivity was 55%, so about half the time nursing personnel
could tell if somebody had
But it has led to development, C.Dif or not.
development, of an artificial or in tnose.ocess of
People think that might be the
somebody has C.Dif. fiIt doesn't have to be wateryif
stool.
takes the shape of the container Semi-formed stool, anything that
is pinfection. of C.Difficile
color are not predictive of Butwhether somebody will haveool
C.Difficile or not. Certain antibiotics, like I
said, are more likely than
There is one thing in recent others.
of interest, and that's the number of white count, or white
cells, in the blood of the
C.Difficile . These people stratified white
count into three different
to 29,000 and then more than strata; 15,000 to 19,000, 20,000
They looked at, in hospitalized people, what were the causes of
that high white count.
about half the people regardless Infection was the major cause in
The rest was things like of which stratum you looked in.
malignancy, leukemia for medications, like hematologic
medications. example, inflammations or
infection. Then they focused on the
the high white count, what type If it'of infection is it?causing
And within the infections there is a number of possibilities in
hospitalized people.
excluded lung infection, which They found that after you've
going to cause a high white count, Clostridium is the most common type that's
urinary tract and soft tissue infections account for the
majority of white count rises.
predictor. This has become an interesting
infectious disease consult in hospitalized people who have a
high white count but nothing
Often times we find it heralds else.
C .Difficile infection which will
become apparent a couple days later but not necessarily at the
time. The white count seems to be an
early predictor of severe C.Difficile infection.
If you were going to diagnose using lab testing the PCR has
really supplanted all the other tests that are mentioned here.
It has a very rapid turn around time, a very high sensitivity
and is very specific as well. The other tests, such as
Eliza's, or a culture, are much more labor intensive and don't
nearly provide the degree of
see in a test like this. accuracy that one would want to
are available on the market. There are many toxin assays that
they don't all detect both It's important to remember that
Toxin A negative but toxin B toxins.
In fact, there was a case at the positive strains been described.
Annuals of Internal Medicine VA that was published in the
had a toxin kit that only looked several years ago where the VA
and the individual had toxin A for toxin A and not toxin B,
eventually, and in an autopsy negatiwas found to have C.Difficile .
When they investigated it further, they found that that
strain would not have been
were doing. deThe toxin B has a roundingey
effect on the cells.
see, on the left they're This is a fiber glass so you can
spindle shape like they should rounded, on the right they're a
There's a lot of infection be.
Clostridium Difficile. control implications for
contamination. There is heavy environmental
but it wasn't always the case Tthat healthcare workers would,
wear gloves when they were
I mean, it seems incredible. dealing with stool.
where this poster was put up on the wards, where they said you
wear gloves when you're dealing with body fluids and excrement
so to speak.
infection control that will reduce C.Difficile?s for
There's some things that have been proven, some that are
highly probable, and some that
Restriction of antiinfectives is have yet been not tested enough.
C.Difficile. clear, that that reduces
has also been shown. Glove use by healthcare workers
as well. Hand washing between patients
precautions or isolation We keep patients in contact
have an individual room, and all precautions, meaning that they
will wash their hands and will healthcare workers that go in
taking care of the individual wwith C.Difficile.ves when
It's very likely that that
hasn't been conclusively shown interrupts transmission, but it
That's why it's probably over at tthere.int.
Treatment of people who are asymptomatic carriers has not
been shown to work. Even though you can eradicate
it briefly, you almost always reacquire it.
Isolation of people who are just
symptoms but are carriers of asymptomatic, don't have
C.Duntested at this point. The reason isolation is of
interest is because, it's not a simple thing first of all, to
keep somebody in contact
studies have shown that there pare adverse effects associated
with keeping people in contact
There is some psychological issues in individuals who may
feel isolated.
healthcare workers are less Alikely to enter the rooms of
patients in contact precautions.
likely translates into worse Now whether entering it less
likely. If you don't see the patient and
you're just waving at them
to learn much. from the door, you're not likely
definitely been a problem with Care from the door has
If you were going to treat C contact precautions.
that we sometimes forget is that thing
trigger. you have to discontinue the
most of the time, when I see Which can sometimes be done, but
antibiotics for a reason, then people in clinic, they're on
and they still need those other antiinfectives.
It's difficult to completely
At the very least, one should make an effort to transfer it to
a different class that is less
C.Difficile . Several randomized trials now,
comparing the two main
One is Vancomycin and one is antibiotics.
Both have equivalent treatment Metronidazole.
similar relapse rates, both are sugiven four times a day. a
Vanocmycin is FDA approved. Metronidazole is not, so it's
off-label use.
dollars. Vancomycin costs thousands of
Vancomycin has hardly any side Metronidazole is very cheap.
Metronidazole can cause neurotoxicity in people, with
numbness and tingling of their
irreversible if it's continued. So they both have their pros and
cons, but like I said, initially
gave people Metronidazole for a whecouple of weeks, things you
resolved. Now that we're seeing people
with prolonged disease, with
them on Metronidazole for a month of so, they will all get
neurological damage and that's
desirable. obviously not something that's
a Clostridium associated Should we use Metronidazole for
Several years ago in Clinical Infectious Diseases there was an
interesting editorial.
somebody has C.Difficile it's perfectly fine to prescribe
Metronidazole for your
something that you would ever mothgive to your mother.not
[laughter]
looked at the outbreaks of C The reason is this, when they
people had almost a 50% reoccurrence rate when they were
given Metronidazole compared
Now, it's unclear why, but many people feel it's because
Metronidazole is absorbed from
blood, and therefore doesn't the GI tract, gets into the
intestine to actually work very hang around well.enough in the
Whereas Vancomycin has no absorption and stays in the
intestine, and therefore does a better job.
I think the answer to that
The recommendations now say that question is still unclear.
than mild disease, you might is somebody has anything more
Metronidazole. prefer Vancomycin to
okay to do Metronidazole as the If it's reafirst one.isease it's
We strongly recommend that
agents, like Lomotil. It's very tempting, because it's
profuse diarrhea, and people
go. But what it does is it keeps the
toxin in the intestine and
makes things worse. We generally tell people not to
use anything that will allow
until the toxin has been their gut to slow down
resolved. expThis study supported that.en
Lincomycin was the older name for Clindamycin, so that same
syndrome of Clindamycin-
randomized people to either getting an antimotility agent or
not, they found that outcomes where worse when they were using
antimotility agents.
asked all the time, because our Tlab works on probiotics fort
reducing Clostridium
So people ask, healthy bacteria, Difficile infection.
can they work against if theC.Difficile?the intestine,
It's pretty clear that they work
diarrhea. Which is why, when anyone gets
antiinfective for any reason, they should always take a
probiatic with it.
weeks after the antibiotics have Then generally take it for two
repopulate. It's not clear which probiotic
one should use. You'll notice this metanalysis
this heterogeneity was pretty high.
Even though the relative risk was almost 50% lower than people
that were taking probiotics.
and the types of probiotics they The studies were so different,
population they used it in, that used, how long they gave it, the
one over the other. They all seem to fairly similar
with the exception of this one, which is Saccharomyces
Boulardii.
subjected to a very rigorous This is the one that was
It was placebo controlled. They had people with randomClostridium blind trial.
Difficile -associated diarrhea, and they gave them a
care, with was Metronidazole, so standard of
C.Difficile, and they gave them either the probiotic some antibiotic to treat
or they gave them placebo. in addition
look at the initial episode, What you found was, that if you
purple there, that there was no real difference between failure
rates whether people were given probiotic or placebo.
But when you look at
and the green lines here, there you can see that people on just
placebo had a much higher failure rate than people who
were given Saccharomyces
Based on this, FDA approval was pursued but eventually was not
granted, mainly because of
and if you give yeast to concerns that this is a yeast,
get yeast in the bloodstream and immunocompromised people you can
Having said that, because it's a that can cause problems as well.
the same regulations as drugs or probiotic, it doesn't come under
So, even though it didn't get FDA approval as a drug, it's
freely available and you can go to any store, Walgreen's, for
example, and buy it for use for C.Difficile.
More recently,
have been found to be helpful. lactobacillus-based preparations
individuals who were at risk for This probiotic was given to
This is DanActive here and C.Difficile twice a day.
This was published in the British Medical Journal.
The primary outcome for this
They looked at C.Difficile group was diarrhea.
But what they found was, in the lower half of that slide, people
that were given probiotic, there
were no cases of C.Difficile .
People that were not given
incidence in the control group probiotic, they had a 17%
ostatistical significance. Based on that, it would seem
that probiotics may have a role to play for prevention of
C.Difficile . They don't seem to have a role,
at least known at this point, of
C.Difficile. adjunctive treatment for
think it's too late at that Opoint, but for prevention it
seems to have value.
because it wasn't very The study has been criticized
Out of the thousands of people generalizable.
hundred met criteria. thThey had a very carefulew
selection group that most of us in this room wouldn't qualify
for.
are needed, but it seems to have I think that's why more studies
I think it should be looked at promise.
The thing you want to avoid with further.
colitis, which is this. C.DiHere is the bowel here.
The black areas are all gas in
Normally it's pretty narrow, and the intestine.
This is very dilated, toxic it loomegacolon.bowel.
The only treatment for that is surgery.
It's not of any value to start
time. In fact, the more you delay, the
more likely they are to not do
Early surgical consideration in ICU patients is really critical.
So, well, what do we do then? We have limited options for
treatment.
work very well. WPeople are getting recurring
disease.
transplant or-- Now, give it a So what about doing a fecal
[laughter] moment.
reaction. I agree, it's not aesthetically
very pleasing, but this study and many since, have looked at,
if you do rectal infusion of
The question came up, what's normal feces.
Who should you get this from? And of course it's always a
spouse, isn't it, that has to volunteer for things like that.
Usually, yes, it should be a
share your same flora. family member who generally
students, but I think that People suggested medical
coercion and that didn't go over came under the heading of
This, you'll notice, is from-- very far.
No, it doesn't. This is from several years ago.
There was no interest to this until recently, but now that
we're stuck in the situation
options, there is a trial wthat's ongoing on fecaled
transplant. There are a lot of institutions
that are doing it.
it does have very good efficacy. It seems to have promise because
want to introduce other pathogens to the individual that
you're giving the stool to. There has to be a fairly
rigorous protocol that's
But in last year's infectious diseases meetings, there were
several abstracts on the utility
C.Difficile , as of fecal transplant for
You know, no production well shortage.okes.
Very little addiction potential.
people will say about this. There's re[laughter]d to what
What we've learned about
C.Difficile then has meant that
new treatments are on the horizon.
So what I was mentioning earlier
If that's low you get severe about the IgG antibody.
Naturally, the next step then was to develop a monoclonal
antibody and give it to people
of recurrence. and see if that reduced the risk
horizon that's not clinically That's oavailable yet.s on the
The newest drug on the market is
recurrences when compared with Fidaxomicin, which has reduced
about $28,000 for 10 day course. Vancomycin, but it also costs
many people that need it. Rifaximin is another antibiotic
that is available.
physically binds the toxin in the intestine and is not yet
available but is in studies to
This New England Journal look at.
with monoclonal antibodies. Again C.Difficile toxin.eatment
This was a infusion that they gave people, and what they found
was, that in the placebo group, recurrence rate was about 25%
and the antibody group was about
That's a substantial decline in the recurrence rate, because
that's when people get sicker and sicker.
They deal with one and they get another recurrence.
Of course, the cycle continues. This is promising.
It's in phase three trials. But is not available.
We don't really know how much the cost will be, but I imagine
it's not going to be slight when
If you use Rifampin-based antibiotics for treatment of
C.Difficile, very quickly, it will become resistant to
Rifampin. That happens with many
of the other antibiotics that we've used for
Surprisingly, there hasn't been a lot of Vancomycin resistance
in C.Difficile thus far.
occur are, in general, said to So most of the failures that
host, you know, if their immune system is compromised then the
antibiotic doesn't do much. This was the publication on
Fidaxomicin verses Vancomycin.
If you look at clinical cure on the left, this is per protocol
and modified intention to treat,
of comparing Fidaxomicin and which is just two different ways
So for clinical cure, they were fairly similar, but look at the
differences in recurrence, which
Fidaxomicin had a much lower is the middle column there.
Vancomycin did. That's what led to the FDA
approval, and that's why it seems very attractive, but we do
restrict it because it's one of the last things we have for
C.Difficile, and in the outpatient setting, it's very
expensive.
tenacity of C.Difficile. Here is a testament to the
had that talked about Clindamycin-associated colitis?
Well, that was a child, a 13-year-old child, that they
took a stool specimen from and
figure out what the cause of sent to the CDC to try and
was at the time. Clindamycin-associated colitis
know, there was a lot of angst The specimen was lost and, you
it and that was that. aThen 21 years later they wentnd
into the archives, they recovered to isolate, it was
still viable and it was still producing toxin, despite having
been stored in probably sub-optimal conditions.
So people have enterprising ways, you know, of doing things.
Recently there has been populations that hitherto
believed to be a low-risk that are now getting
C.Difficile.
peri-partium women which felt Tthat if they get antibioticss
because they're carrying, say,
rectal area, they'll get group B strep in vaginal or
Clindamycin to protect the penicillin or they'll get
Then they'll get Clindamycin. Or the neonate who will be
colonized with
then get severe C.Difficile. to the mom, who will
diagnosis there, because you And probably a delay in
know-- Here's the first case. This is a 31-year-old woman who
was 14 week pregnant with twins and then got C.Difficile.
That's not a population that you
risk. But I think it's a reflection of
how severe the disease has
strains are. become and how virulent the
normally should be able to That it's affecting people that
Finally, this is a situation protect themselves.
your best friend. This was where a dog may not always be
strain in a hospital visitation an epidemic Cdog.ficile
Many healthcare institutions
programs and policies, and have hospital visitation dog
in people who are rehabbing from they're clearly of great value
syndromes. strokes or other neurologic
that sometimes you can get But it seems to be very possible
If not C.Difficile, inf but others as well. well.
Just something to keep in mind. I think that's all I have.
I'm happy to take questions, and
[applause]