CDC urges physicians to consider this diagnosis in patients with
severe diarrhea, even if they don’t have traditional risk factors.
by Marie Rosenthal
IDC Editor in Chief

http://www.idinchildren.com/200608/frameset.asp?article=difficile.asp

August 2006WASHINGTON – Clostridium difficile is following the path of
methicillin-resistant Staphylococcus aureus (MRSA) – out the
hospital door and into the community. In addition, strains are becoming more virulent and resistant, and
are starting to affect non-traditional populations, such as
children, according to Trish M. Perl, MD, director of hospital
epidemiology and infection control at Johns Hopkins in Baltimore.“What happened is this disease remade itself – it got a face-lift,”
Perl said at a press briefing sponsored here by the National
Foundation for Infectious Diseases. “The perception is that there is
an increase in incidence of this, and it has emerged in the
community. We also think there is an increase in disease severity.”

This gram-positive, spore-forming bacillus, which produces
exotoxins, is a leading cause of nosocomial infections,
traditionally in the elderly or severely immunocompromised
patients. “It is the most commonly reported enteric pathogen and it
is the leading cause of nosocomial diarrheal diseases,” Perl
said. “It has been well described to cause epidemics, but it is
actually quite endemic.”

Associated with antibiotic use, C. difficile diarrhea used to be
only considered a nuisance in the health care setting, but Perl said
she would not characterize it as such today. “It truly is much more
than a nuisance; I think that is an underestimate of its
importance,” she said.

The organism colonizes the gastrointestinal tract and at any given
time, 3% of the population is colonized. “If we look at neonates
almost all of them are colonized. So it is something that normally
hangs out in the GI tract,” she said. Antibiotic exposure alters the
flora of the GI tract and can lead to proliferation of the C.
difficile.

Carol Baker, MD, a pediatric infectious disease physician at Texas
Children’s Hospital, said that she is also seeing C. difficile in
children. “We also have begun to see C. difficile in kids,” she
said. This was “something I did not see previously, except in
adolescents with cystic fibrosis and years of antibiotic exposure.”

“The CDC’s Morbidity and Mortality Weekly Report described several
cases of community-acquired C. difficile-associated disease (CA-
CDAD) among 23 healthy residents in the community and 10 peripartum
women, two populations previously considered at low-risk for CDAD.
The CDC highlighted some of the cases.

The first case involved a pregnant woman, 31, who presented at a
local emergency department with a history of three weeks of
intermittent diarrhea, followed by three days of cramping and
watery, black stools. She reported one antimicrobial exposure, a
course of trimethoprim-sulfamethoxazole (TMP-SMX) for a urinary
tract infection three months earlier. She was discharged after
receiving metronidazole. The next day, she was readmitted and spent
18 days in the hospital for treatment of severe colitis; she
received metronidazole, cholestyramine and oral vancomycin. She
improved and was discharged, but was readmitted with diarrhea and
hypotension. She lost the twins she was carrying and despite
aggressive treatment, she died. Histopathology of the colon showed a
megacolon with pseudomembranous colitis.

Another case involved a 10-year-old girl who presented to a local
children’s hospital with intractable diarrhea, projectile vomiting,
abdominal pain and fever. She had no history of antibiotic use
during the preceding year. “The child had been healthy until two
weeks before the ED visit, when she became symptomatic within days
of her younger brother having a febrile diarrheal illness,” the
report said.

After a week of illness, a clinician performed a rapid strep test,
which was positive. She received amoxicillin, but could not keep it
down. She was admitted to the hospital and received intravenous
fluids, electrolytes and metronidazole; her symptoms finally
resolved.

“This was very unusual. I’m not a pediatrician; I’m an adult
infectious disease doctor. But there are pediatricians here who
would tell you that this is not a common disease in children. This
is really an adult disease. So, this was very unusual,” Perl said.

Another remarkable trend in the CDC report was that 24% of the
reported cases had not received antibiotics.

The CDC report suggested that clinicians “consider the diagnosis of
CDAD in patients with severe diarrhea even if the patients do not
necessarily have traditional risk factors, such as recent
hospitalization or antimicrobial use.”

The mortality associated with this disease appears to be increasing,
too. Perl said that when she was in training, it was highly unusual
for someone to die from C. difficile. Today, it is more likely to
happen. In 2000, one Pittsburgh institution reported that life-
threatening C. difficile almost doubled with 44 colectomies and 20
deaths, Perl said. Data from Portland, Ore. indicated that mortality
from C. difficile rose from 3.5% to 15%.

The reason is a new toxic strain called NAP1/B1 toxinotype III.
According to a report by the CDC, “the epidemic strain produces 16
times more toxin A and 23 times more toxin B compared with other
common strains. 

“Virulent strains, which cause more severe disease in populations at
high risk, might also cause more frequent, severe disease in
populations previously at low risk (eg, otherwise health persons
with little or no exposure to health-care settings or antimicrobial
use),” the CDC went on to explain.

Research done in Quebec “helped us wake up to the potential change
in the epidemiology that was going on with severe outcomes and
deaths,” Perl said. The strain seen in Quebec has moved south into
the United States and is being seen in pockets of this country,
particularly in the Mid-Atlantic region. Seventeen states have
reported this toxic strain, she said.

Quebec reported that C. difficile rates increased from 36 per
100,000 population to 156 per 100,000 population between 1991 and
2003. “I also would point out that they showed similar data as that
reported by Portland with a similar mortality increase, so the same
kind of pattern is emerging – a tripling of the mortality associated
with the disease,” Perl said.

Fluoroquinolones traditionally have been associated with a fourfold
increase in CDAD, but other antibiotics, especially clindamycin, are
also putting patients at risk. Clindamycin is now a favored drug to
deal with community-associated MRSA; but in some communities, it
might not be the best choice, she said.

“As an adult ID doc, we use a lot of TMP-SMX in this particular
setting. It is not as well liked [in pediatrics], but the
pediatrician certainly will use that,” Perl said.

“I don’t know that any of us at this point think that emergence of
C. diff is related to the clindamycin that we have been using for CA-
MRSA,” she cautioned. “But we have to be vigilant and we have to
watch for unintended consequences of anything that we do.”

Controlling CDAD
She said new practice guidelines are being developed to try to
control CDAD. One institution restricted fluoroquinolone use and saw
a decrease in C. difficile.

“There may be a push to restrict these other agents that have been
implicated, particularly, clindamycin,” she said.

Institutions should enforce hand washing with soap and water and the
use of gloves by anyone caring for a patient in the community. “It
is going to become more important not only in the health care
setting, but in the community, if these community cases are truly a
new wave of this disease,” she said.

Cleaning the environment is also important, but it is difficult
because the spores linger in the environment for a long time. New
technologies are needed to solve this problem, she said.

“Bleach clearly works very well, but it is destructive to equipment,
and when used in high concentrations, it burns your eyes. That is
not well tolerated in day care settings, hospitals or long-term care
facilities,” she said.

In addition to new cleaning methods, immune globulin, a promising
vaccine, and strategies to decolonize the patient are being studied
for treatment.

The disease may increase the average patient cost by $3,600 per
patient, Perl said.

For more information:
CDC. Severe Clostridium difficile-associated disease in populations
previously at low risk – four states, 2005. MMWR. 2005:54(47);1201-
1205 

As mentioned above, C. Difficile is a also a biotoxin producing bacteria and may play a role in chronic fatigue and fibromyalgia.  An online screening test for biotoxin exposure has been developed by Dr. Ritchie Shoemaker; more info at www.biotoxin.info.