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TheAnswerPage/Hospital & Critical Care Medicine
Monday
February 08, 2010
This week:
Clostridium difficile
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What is Clostridium difficile?
C. difficile is an anaerobic, spore-producing gram-positive
rod originally isolated from healthy newborn intestinal flora. Spores
are able to survive gastric acidity, converting to vegetative forms
in the lower gut. The latter secrete two potent toxins (A and B)
which disrupt the cytoskeleton of mucosal epithelial cells and result
in abnormal intestinal secretory activity and inflammation.
Interestingly, a significant proportion of healthy neonates harbor
toxin-producing C. difficile but do not develop colitis. By
contrast, asymptomatic carriage rates are much lower in
non-hospitalized (<10%) and hospitalized (~20%) adults. Resistance
of neonates to disease may be related to decreased intestinal
expression of toxin A receptors as well as decreased chemotactic
responses of granulocytes.
The spores of C. difficile are hardy and can survive for
prolonged periods in the environment (soil, water, animals, hands,
clothes, stethoscopes, rooms of infected individuals).
What are the clinical manifestations of C. difficile
infection?
C. difficile causes a spectrum of disease ranging from
asymptomatic carriage to diarrhea, pseudomembranous colitis, and even
fulminant colitis. The typical patient has received 5-10 days of
antibiotics, subsequently developing fever, crampy abdominal pain,
diarrhea, and leukocytosis (mean 12,000 - 20,000 per mm3). Ancillary
features include nausea, vomiting, and dehydration. In severe
disease, the patient may develop peritoneal signs and toxic
megacolon. As Eleftherios et al. (2001) point out, however, if
disease involves the cecum or right colon or if the patient develops
a paralytic ileus, there may be little or no diarrhea.
Occasionally, patients may exhibit a "leukemoid reaction"
characterized by an extremely elevated leukocyte count (as in the
present case). In the appropriate setting, this finding is often
suggestive of C. difficile colitis.
Question Author: Frederick S Lee, MD, PhD
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References:
- Bulusu M, Narayan S, Shetler K, Triadafilopoulos G.
Leukocytosis as a harbinger and surrogate marker of Clostridium
difficile infection in hospitalized patients with diarrhea. Am J
Gastroenterol 95:3137-41 (2000).
- Eglow R, Pothoulakis C, Itzkowitz S, Israel EJ, O'Keane CJ,
Gong D, Gao N, Xu YL, Walker WA, LaMont JT. Diminished Clostridium
difficile toxin A sensitivity in newborn rabbit ileum is
associated with decreased toxin A receptor. J Clin Invest 90:822-9
(1992).
- Eleftherios, M., Ryan, E.T., and Calderwood, S.B. Clostridium
difficile associated diarrhea: a review. Arch Intern Med
161:525-533 (2001).
- Just I, Hofmann F, Aktories K. Molecular mode of action of the
large clostridial cytotoxins. Current Topics in Microbiology and
Immunology 250: 55-83 (2000).
- Kelly CP, LaMont JT. Clostridium difficile infection. Annu
Rev. Med. 49:375-390 (1998).
- McFarland LV, Mulligan ME, Kwok RY, Stamm WE. Nosocomial
acquisition of Clostridium difficile infection. N Engl J Med
320:204-10 (1989).
- Thelestam M, Chaves-Olarte E. Cytotoxic effects of the
Clostridium difficile toxins. Current Topics in Microbiology and
Immunology 250: 85-96 (2000).
- Thielman, NM. Antibiotic-associated colitis. In: Principles
and Practice of Infectious Diseases, 5th ed, Mandell, GL, Bennett,
JE, Dolin, R (Eds), Churchill Livingstone, New York 2000.
- Triadafilopoulos G, Shah MH, Pothoulakis C. The chemotactic
response of human granulocytes to Clostridium difficile toxin A is
age dependent. Am J Gastroenterol 86:1461-5 (1991).
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M.D.
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