Literature on the Management of Clostridium difficile-Associated Disease: Commentary by Dr. John G. Bartlett -- April 2007

John G. Bartlett, MD


April 24, 2007

Lamontagne F, Labbe AC, Haeck O, et al. Impact of emergency colectomy on survival of patients with fulminant Clostridium difficile colitis during an epidemic caused by a hypervirulent strain. Ann Surg. 2007;245:267-272. The study investigators examined the potential value of emergency colectomy in patients with fulminant Clostridium difficile-associated colitis.

Methods: The authors retrospectively reviewed an observational cohort of 165 patients with C difficile-associated colitis who required admission to the intensive care unit (ICU) between 2003 and 2005 in 2 hospitals in Sherbrooke, Canada.

Results: Among those who were seriously ill, the mortality was 87/165 (53%). Among those who underwent emergency colectomy, the mortality was 5-fold less (odds ratio = 0.2) and this procedure seemed most beneficial in those age 65 years or older. Risk factors associated with increased mortality are summarized in Table 1 .

Conclusions: The authors concluded that emergency colectomy decreases mortality in patients with fulminant C difficile-associated colitis.

Comment: The obvious concern with this type of retrospective analysis is the potential for bias in those selected for surgery. Nevertheless, this is the first such analysis with a comparison group in patients who were seriously ill with C difficile-associated colitis.

Pepin J, Routhier S, Gagnon S, Brazeau I. Management and outcomes of a first recurrence of Clostridium difficile-associated disease in Quebec, Canada. Clin Infect Dis. 2006;42:758-764. The goal was to determine the relative merits of metronidazole and oral vancomycin in the treatment of patients with a relapse following C difficile-associated diarrhea.

Methods: The study investigators reviewed data for patients with C difficile diagnosed in Quebec using their database for the period 1991 through 2005 for Sherbrooke Hospital. Treatment consisted of metronidazole, 250 mg 4 times daily or 500 mg 3 times daily for 10-14 days, or oral vancomycin 125 mg 4 times daily for 10-14 days. The diagnosis was based on positive toxin assay of stool, evidence, pseudomembranous colitis (PMC) by endoscopy, or histopathology of a biopsy.

Results: There were 463 patients with a relapse according to the protocol definition, and 154 (33%) had a second recurrence. Of these, 286 were treated with either oral vancomycin or metronidazole; the rate of relapse was approximately the same in both groups, as shown in Table 2 .

Risk factors for the second occurrence were limited to age and duration of hospitalization. The analysis showed no relationship according to hospital-acquired vs community-acquired infection, the period of the diagnosis (1991-2002 vs 2003-05), immunosuppression, or the peak leukocyte count. Data for significant associations are summarized in Table 3 .

Conclusions: The authors concluded that oral vancomycin and oral metronidazole are equally effective for the treatment of first recurrences after C difficile-associated diarrhea.

Comment: The study investigators showed essentially no difference in the rate of second relapses following oral vancomycin or metronidazole treatment of the initial relapse. However, this is actually not the most important question to ask. The major controversy is the relative merits of these drugs for response in patients with serious disease. In the present study, the rate of serious complications was 51/463 (11%) including shock (10 patients), colectomy (3), toxic megacolon (2), and death within 30 days (43). The authors note that these complications occurred less frequently with vancomycin than with metronidazole, but no specific results were given and the difference was not statistically significant (P = .09).


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