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Research at Hines Aims to Prevent Outbreaks Due to Increasingly Resistant Hospital Germ
For decades, hospitals have
contended with a potentially nasty germ called Clostridium difficile. The bacterium tends to proliferate and cause disease in hospital patients who acquire it after having been on antibiotics, which disrupt protective normal bowel flora. Infection with C. difficile is one of the most common hospital acquired infections worldwide, and in the United States alone it causes some 400,000 cases of diarrhea and colitis each year in hospital patients.
In a Dec. 8, 2005, New England Journal of Medicine article, a team of researchers including Dale Gerding, MD, and Stuart Johnson, MD, from the Hines VA Medical Center reported on a previously uncommon strain of C. difficile—known as the BI/NAP1 isolate—that appears to be the culprit in an emerging epidemic of
C. difficile-associated disease, or CDAD. The strain is a particularly toxic form of C. difficile, and now appears the most likely suspect in a string of increasingly deadly CDAD outbreaks that has plagued Canadian and U.S. hospitals in recent years.
Gerding and colleagues collected 187 isolates from eight U.S. hospitals
where outbreaks occurred between
2000 and 2003, and analyzed them
against his database of more than
6,000 historical strains of C. difficile.
The isolates were also tested for
toxicity and antibiotic resistance.
"We were able to identify the
outbreak strain within our library of
typed strains and document that these
strains were found in the 1980s and
1990s, but did not cause epidemics
then, as they were not yet resistant to
the new fluoroquinolone antibiotics"
said Gerding.
The newly obtained samples of BI/NAP1, however, showed universal
resistance to fluoroquinolones—a
large family of broadspectrum antibiotics
that have been used by hospitals
since the late 1980s to treat a wide
range of infections.
"The new strains have acquired this
resistance," noted Gerding, "and it may
be an important reason why they are
now disseminating widely."
Better infection control methods in
hospitals may be one part of the
solution. Another may be more prudent
use of fluoroquinolones.
"Inappropriate use of antibiotics is
at the heart of the CDAD problem in
my view," said Gerding. He points out
the need for "careful studies of
antibiotic restriction when specific
with CDAD cases." He says past
studies have shown success in restricting
the use of clindamycin and other
antibiotics, but restricting use of the
widely used fluoroquinolones may
prove a tougher challenge.
That’s why Gerding is especially
hopeful about his research with
"friendly" strains of C. difficile, which
has been supported through VA Merit
Review grants. The theory is that by
intentionally colonizing the colon with
nontoxic strains of C. difficile,
doctors will be able to prevent the toxic
types—including the now notorious BI/NAP1—from thriving.
Based on very successful hamster
studies, in which CDAD mortality
dropped from 100 percent to less than
3 percent, Gerding says, "We think that
the nontoxigenic strains obtained from
asymptomatic hospitalized patients are
able to colonize the GI tract following
antibiotic use, and once established,
will keep out toxigenic strains." He
holds patents for his methods in the
United States, Canada and Europe, and
is licensing them to a pharmaceutical
company for development. He hopes
to be conducting clinical trials within
two years.
"If nontoxigenic C. difficile works
in humans like it does in hamsters, I
believe we will be able to significantly
reduce, if not eliminate, CDAD as a
significant hospital infection problem,"
said Gerding. "This will fulfill my
ultimate dream after 25 years of doing
research on C. difficile."
McDonald LC, Killgore GE, Thompson A, Owens RC Jr, Kazakova SV, Sambol SP, Johnson S, Gerding DN.
An epidemic, toxin gene-variant strain of Clostridium difficile.
N Engl J Med. 2005 Dec 8;353(23):2433-41. Epub 2005 Dec 1.
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