CMAJ • August 31, 2004; 171 (5). doi:10.1503/cmaj.1041104.
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Clostridium difficile-associated diarrhea in a region of Quebec from 1991 to 2003: a changing pattern of disease severity

Jacques Pépin, Louis Valiquette, Marie-Eve Alary, Philippe Villemure, Annick Pelletier, Karine Forget, Karine Pépin and Daniel Chouinard

From the Department of Microbiology and Infectious Diseases, University of Sherbrooke, Sherbrooke, Que.

Correspondence to: Dr. Jacques Pépin, Centre hospitalier universitaire de Sherbrooke, 3001, 12e Avenue Nord, Sherbrooke QC J1H 5N4; fax 819 820-6451; jacques.pepin{at}usherbrooke.ca

Background: Recent reports suggest that Clostridium difficile colitis may be evolving into a more severe disease. During the second half of 2002 we noted an increase in the number of patients with severe C. difficile-associated diarrhea (CDAD) in our institution. We describe cases of CDAD at our institution over a 13-year period and investigate changes in illness severity.

Methods: We undertook a retrospective chart review of all cases of CDAD diagnosed at the Centre hospitalier universitaire de Sherbrooke from Jan. 1, 1991, to Dec. 31, 2003. Because the hospital serves a well-defined population of Quebec, we were also able to calculate population-based incidence during this period. We abstracted data on individual patients from patient charts and from hospital and pharmacy computer databases. We defined cases of CDAD as having a positive C. difficile cytotoxicity assay result, or endoscopic or histopathological evidence of pseudomembranous colitis. A case was considered complicated if one or more of the following was observed: megacolon, perforation, colectomy, shock requiring vasopressor therapy, or death within 30 days after diagnosis.

Results: A total of 1721 cases of CDAD were diagnosed during the study period. The incidence increased from 35.6 per 100 000 population in 1991 to 156.3 per 100 000 in 2003; among patients aged 65 years or more, it increased from 102.0 to 866.5 per 100 000. The proportion of cases that were complicated increased from 7.1% (12/169) in 1991–1992 to 18.2% (71/390) in 2003 (p < 0.001), and the proportion of patients who died within 30 days after diagnosis increased from 4.7% (8/169) in 1991– 1992 to 13.8% (54/390) in 2003 (p < 0.001). A high leukocyte count (20.0 109/L or greater) and an elevated creatinine level (200 µmol/L or greater) were strongly associated with adverse outcomes: in 2003, 45 (40.9%) of 110 patients with a high leukocyte count or creatinine level, or both, had complicated CDAD and 28 (25.5%) died within 30 days after diagnosis. After adjustment for age and other confounding factors, patients initially given oral vancomycin therapy had a risk of progression to complicated CDAD that was 79% lower than the risk among patients initially treated with metronidazole (adjusted odds ratio 0.2, 95% confidence interval 0.06–0.8, p = 0.02).

Interpretation: An epidemic of CDAD with an increased case-fatality rate has had important consequences on the elderly population of our region. Our observational data suggest that the equivalence of vancomycin and metronidazole in the treatment of CDAD needs to be questioned.




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How should we respond to the highly toxogenic NAP1/ribotype 027 strain of Clostridium difficile?
Can. Med. Assoc. J., October 25, 2005; 173(9): 1049 - 1050.
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J. Pepin, L. Valiquette, and B. Cossette
Mortality attributable to nosocomial Clostridium difficile-associated disease during an epidemic caused by a hypervirulent strain in Quebec
Can. Med. Assoc. J., October 25, 2005; 173(9): 1037 - 1042.
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J. Starr
Clostridium difficile associated diarrhoea: diagnosis and treatment
BMJ, September 3, 2005; 331(7515): 498 - 501.
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N. Dendukuri, V. Costa, M. McGregor, and J. M. Brophy
Probiotic therapy for the prevention and treatment of Clostridium difficile-associated diarrhea: a systematic review
Can. Med. Assoc. J., July 19, 2005; 173(2): 167 - 170.
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E. Weir and K. Flegel
Protecting against Clostridium difficile illness
Can. Med. Assoc. J., April 26, 2005; 172(9): 1178 - 1178.
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J. Pepin
Strains and toxins of Clostridium
Can. Med. Assoc. J., February 1, 2005; 172(3): 313 - 313.
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D. C. Vinh
Strains and toxins of Clostridium
Can. Med. Assoc. J., February 1, 2005; 172(3): 312 - 313.
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I. R Poxton
Clostridium difficile
J. Med. Microbiol., February 1, 2005; 54(2): 97 - 100.
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Nosocomial infections: What needs to be done?
Can. Med. Assoc. J., August 31, 2004; 171(5): 421 - 421.
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Les infections nosocomiales : que faut-il faire?
Can. Med. Assoc. J., August 31, 2004; 171(5): 423 - 423.
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Clostridium-Associated Diarrhea
Donald C. Vinh
CMAJ, 13 Sep 2004 [Full text]