Now let's talk about the antibiotics that we need to worry about. The ones that seem to be
frequently linked to antibiotic-associated colitis are ampicillin and amoxicillin, the cephalosporins,
the clindamycin and particularly the fluoroquinolones and these organisms are fairly broad
spectrum. Less frequently, we talk about the tetracyclines, sulfonamides, erythromycin. We
don't use much chloramphenicol in the United States anymore and trimethoprim and I'll start out
by saying that I have never recognized antibiotic colitis due to an aminoglycoside. The
aminoglycosides like gentamicin essentially only hit aerobic gram-negative rods for all practical
purposes and it must be as rare as hen’s teeth for metronidazole to cause antibiotic colitis
because metronidazole and vancomycin are two of the treatments we use to kill C. difficile.
So I've never seen it but it's on the list as a rare cause. Now this organism, Clostridium difficile,
like other Clostridia is a spore-forming organism. So when it falls upon hard times even in the
intestine, it may form spores which allow it to survive under environmental circumstances that
are unfavorable to the organism and it's these spores that can be ingested and also can
disseminate and that dissemination sometimes takes place even in the hospital and they can
colonize the surface when antibiotics have altered their colonization resistance. So let's say
somebody is receiving an antibiotic that even works against Clostridium difficile or the organism
may form spores and the spores are essentially impervious even to antibiotics that kill
C. difficile. So in the hospital, if someone has antibiotic colitis caused by this bacterium,
we need to isolate the patient so barrier precautions are needed. So this organism makes
essentially 3 toxins. It makes an A toxin, TcdA, which would be toxin of C. difficile A.
TcdB and it's really the B toxin that's the bad boy, it's a thousand times more potent than the
A toxin and then it makes a binary toxin that is very mild in terms of its effect on the GI mucosa.
So what the toxin does is it glycosylates and inactivates GTPases and GTPases are enzymes
which control actin cytoskeleton of cells. If you disrupt the actin cytoskeleton, you're going to
kill the cell. You also, in killing the cells, disrupt the barrier function of the mucosa and the cells
either directly are killed or they become apoptotic and it's no surprise that you get an
inflammatory response with an infection caused by C. difficile. So the toxins enter
the cytoplasm. They then glycosylate the RhoB protein, which is the regulator of the actin
cytoskeleton. They disrupt the actin cytoskeleton and kill the cell. So let's talk about the
spectrum of disease. The expression of the disease how severe it is depends upon the host's
susceptibility or the immunity. Some strains are more virulent than others and the timing and
the type of antibiotic therapy, for instance if you started somebody on ampicillin and they
received a short course, well C. difficile may try to overgrow but after stopping the
antibiotic, the other organisms come back quickly and the diarrhea resolves spontaneously. It was
due to C. difficile but it was self-limited. So, the other thing is that antibiotic-associated
diarrhea may have other causes. You can also carry C. difficile as I like to say the
students down there in the dark asymptomatically. I would guess a sizable minority of us have
this organism, maybe 30% of us have this organism in our intestine now. Then there's the
diarrhea that starts the C. difficile associated diarrhea and if it's progressive it will become
pseudomembranous colitis and it can result in fulminant colitis with toxic megacolon and death.
So how do you diagnose antibiotic-associated colitis. Well, you have to demonstrate that the
toxins are in the stool. We do that commonly using an enzyme immunoassay and we ordinarily
submit 2 specimens and if you do that the sensitivity is greater than 90% so we can easily
diagnose this. Now, if the diagnosis remains in doubt or let's say we know the patient has it
but they are no better, it may be time to do a lower GI endoscopy and that's where we see
this pseudomembranous colitis. Now, they call it pseudomembranous colitis, it's a very
adherent not pseudomembrane, not a real membrane, composed of white cells and the
sloughed mucosal epithelium. That's what you're looking at.
So how do we manage antibiotic associated colitis?
Well, if the initial episode is mild or moderate,
with a white cell count less than 15,000
and normal renal function,
the recommended treatment is either oral vancomycin or oral fidaxomicin
If neither of these drugs are available
metronidazole can be given.
If the case is more severe, with a white cell count over 15,000
and reduced renal function,
the same first line treatments are recommended,
but oral metronidazole is no longer considered an appropriate treatment.
If the patient goes on to develop hypertension, shock,
or develops an ileus, we can escalate treatment to
oral vancomycin plus IV metronidazole
If the ileus is present,
we can consider rectal administration
of the vancomycin
as well as a fecal microbiota transplant.
If the infection recurs,
your antibiotic selection is determined partially
by the previous treatment.
If vancomycin was initially used,
you can try pulse-tapered vancomycin, or fidaxcomicin.
If on the other hand, vancomycin was not used for the initial infection,
it will become the first-line treatment for the recurrence.
If the patient develops a second recurrence,
your choices would be either pulse-tapered vancomycin,
fidaxomicin, vancomycin followed by rifaximin,
or a fecal microbiome transplant.
What's really promising in the treatment of
particularly severe or recurrent C. difficile infection
is giving. I know it sounds terrible,
a fecal transplant from people who donate normal stool.
And the idea is that normal stool contains other bacteria,
that once they get into the colon,
will quiet down the growth of C. diff.
And initially, the way to give it was not very satisfactory.
We'd give it through a colonoscope by retention enema.
Or actually put feces down a nasogastric tube.
Or there are now some oral capsulized frozen fecal samples
that we can give like a pill.
And believe it or not, as strange as this might sound,
and they are highly effective in preventing multiple recurrences.
So, I think, the trend now is to figure out a way
to do this more aesthetically pleasing.
And the things that are uncertain are
what actually organisms in feces, do the protection?
We don't know that.
And there are some experimental things by Series Health Ser-109.
It's a combination of bacterial spores in pill form
And, it's not ready for primetime
but it's promising for recurrent C. diff infections.
So, that's a lot about C. difficile, but it needed a lot of discussion
because of the importance of this in modern medicine.