Recurrent Clostridium Difficile (Antibiotic Diarrhea)
Modern antibiotics are powerful drugs and often lifesaving, but, as with
all medications, side effects may sometimes occur. One side effect of
antibiotic therapy is diarrhea. This is often called
antibiotic-associated diarrhea. Other names for this condition are
antibiotic-associated colitis, pseudomembranous colitis, or Clostridium
difficile colitis. This infection is caused by a disruption of the
normal bacterial content of the large intestine resulting in a loss of
the normal healthy bacteria. Most cases follow a course of antibiotic
therapy, but sporadic cases can occur. In either event, this disruption
allows an overgrowth of the Clostridium difficile bacteria which
produces a toxin. This toxin damages the lining of the large intestine
causing the symptoms. These symptoms include diarrhea with many loose
watery bowel movements during the day and often at night. Some cases are
more severe with fever abdominal pain, nausea and vomiting, Treatment
requires an additional antibiotic to kill the disease bacteria so the
healthy bacteria can return. Most often Flagyl (metonidazole) and
Vancocin (vancomycin) are used. Most individuals see improvement in 3-5
days with resolution of symptoms by the end of the 10th day of
treatment.
Why Does Clostridium difficile Infection Reccur?
Unfortunately, about 20% of patients with C. difficile infection have a
recurence of the infection after they finish a course of appropriate
treatment - even if they are not exposed to more antibiotic therapy.
There does not appear to be any relationship between recurrence and the
severity of the original infection or the treatment used. It does seem
that recurrent disease is slightly more common in older women, kidney
disease, and chemotherapy. Of course, taking antibiotics for another
infection will increase the risk of recurence. Most affected are adults,
but recurrent C. difficile has been reported in children.
The major risk factor of recurrent infection, however, is a prior
recurence. After the first recurrence about half of the patients
continue to have repeated episodes often over a period of years.
Recurrent disease can be caused by germination of residual C. difficile
spores that are not killed and remain in your colon after treatment.
Reinfection with a new strain of C. difficile occurs when a susceptible
individual is exposed to a new source of C. difficile. This might occur
during readmission to a nursing home or hospital where C. difficile is
present. It is estimated that about 16% of hospitalized patients harbor
this bacteria within their colon as inactive spores. This number is
probably higher in long term care facilities. In this "carrier state"
there are usually no symptoms.
The time interval between the first infection and a recurence varies but
most occur in the first 4 weeks after treatment is ended. If more than 3
months have elapsed, it is more likely a separate unrelated episode.
Symptoms of Recurrent C. difficile Infection
The symptoms are the same as the original infection with frequent watery
diarrhea many times during the day and night. The stools are often have
a characteristic foul odor and color.
A mild case may have 5 to 10 watery bowel movements per day, no
significant fever, and only mild abdominal cramps. Blood tests may show a
mild rise in the white blood cell count up to 15,000. (Normal up to
10,000)
Severe cases may experience more than 10 watery stools per day,
nausea, vomiting, high fever 102-104 F, rectal bleeding, severe
abdominal pain with much tenderness, abdominal distention, and a high
white blood count of 15-40,000.
How is Recurrent C. difficile Diagnosed?
Recurrent C. difficile is defined as a return of diarrhea symptoms after
a course of treatment with demonstration of the C. difficile toxin in a
stool specimen. Sometimes a flexible sigmoidoscopy "scope" test is done
to assess how severe the infection might be. Your doctor may see
characteristic creamy white or yellow plaques adherent to the wall of
the colon. Biopsies may help confirm this. In mild cases, these findings
may not be present. In about 20% of cases, it is also possible to have
recurrent C. difficile infection with a perfectly normal sigmoidoscopy
exam. Usually though, all your doctor usually needs are a description of
your symptoms and a lab analysis of a fresh stool specimen. It is not
normal to have the C. difficile toxin in your stool. A positive test
means infection. You should know, however, that the standard immunoassay
for the toxin only has about a 65% accuracy and may miss about
one-third of cases. So if your symptoms strongly suggest recurrence,
your doctor may retreat you even if the stool test and sigmoidoscopy are
normal.
Complications
In addition to all the usual symptoms, C. difficile infection can lead
to a serious condition called toxic megacolon. In this instance, the
colon is so damaged that the wall weakens and the colon becomes dilated,
sometimes it will rupture causing a life-threatening case of
peritionitis. Fortunately, this complication is quite rare.
Treatment
For the original infection, the two most common antibiotics to treat C.
difficile are Flagyl (metonidazole) and Vancocin (vancomycin). Flagyl is
usually given orally four times a day for 10 days. It is less expensive
and has a high cure rate for the first infection, but often has side
effects of nausea, a metallic taste in the mouth. It can not be taken
with alcohol in any form or during any stage of pregnancy. It is
considered first line therapy. Vancocin is usually also given orally
four times a day for 10 days. Side effect are less common since it is
not absorbed into your bloodstream. But, Vancocin is very expensive and
its use is limited due to the emergence of other Vancocin-resistance
organisms. It is considered a second line drug.
The same drugs are used to treat recurrent C. difficile. But, recurrent
C. difficile is difficult to treat because the spores of C. difficile
are not susceptible to antibiotic therapy. Often your doctor will use a
tapering course of therapy or pulse therapy which may help to destroy
any remaining spores as they germinate.
Cholestryamine resin (Locholest, Questran, Colestid) is sometimes
combined with antibiotic therapy. This medication is marketed to lower
cholesterol, but may also be of some help by binding and eliminating the
C. difficile toxin from the intestine. Cholestryamine is a powder that
is mixed with water and usually taken by mouth once or twice a day. It
can cause some bloating and can not be taken within two hours of any
other prescription drug including antibiotics.
Probiotic therapy is an exciting new development in the treatment of
recurrent C. difficile. Preliminary clinical studies suggest that these
agents may help restore the normal healthy intestinal bacteria and
increase resistance to the growth of C. difficile. Sevral agents have
been studied including Saccharomyces boulardii, a non-disease yeast that
inhibits the growth of C. difficile and may help inactivate its toxin.
Saccharomyces boulardii is a live yeast packaged in capsules and sold
over the counter as Florastor to treat diarrhea; millions of doses are
sold each year. SB does not remain in the intestine and is eliminated
from the body within several days. SB is a different yeast than candida,
which causes oral and vaginal yeast infections, or thrush.
Saccharomyces boulardii does not increase thrush and in fact may lessen
or prevent thrush infections.
Another helpful probiotic organism is Lactobacillus. We often tell our
patients to eat yogurt with an active lactobaccilus culture (such as
Dannon Yogurt) during and after their course of therapy. A more
effective form of lactobacillus may be Culturelle, or Lactobacillus
casei GG which is available on the web at www.culturelle.com. You can
purchase about a month's supply of 100 capsules for about $55. This
unique strain takes it name from its discoverers, Drs. Gorbach &
Goldin of Tufts University in Boston, Massachusetts who analyzed over a
thousand different strains and chose the LGG strain as the ideal
probiotic. Stomach acid often kills bacteria before they enter the
intestine below. LGG has been proven to better withstand stomach acid
and form a stronger barrier to bad bacteria than other Lactobacillus
varieties.
The Future
With the recent availability of more powerful broad-spectrum
antibiotics, the incidence of C. difficile and recurrence disease has
increased. Hospitals and nursing homes, are know reservoirs of the C.
difficile where a susceptible individual may acquire the infection. As
our "baby boomer" population ages and enters long-term care facilities,
the problem is likely to worsen. This disease is costly and often
difficult to treat. Prevention lies on restraint in antibiotic use,
environmental decontamination, and patient education. Probiotic therapy
may become a major benefit in the future.
