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The article by Ananthakrishnan et al (Gut 2008;57:205–10) has suggested that there is increased morbidity and mortality in hospitalised patients with inflammatory bowel disease (IBD) who are concomitantly infected with Clostridium difficile compared with hospitalised IBD patients without infection. Such large epidemiological studies are powerful tools for identifying statistically significant associations, but must be tempered with caution when they attempt to explain causality. From the data presented we do not believe that it is possible to conclude that C difficile infection confers a greater risk of death in hospitalised patients with IBD. Importantly, there is no information regarding disease extent in the “infected” and “uninfected” IBD populations. It is plausible that disease extent, particularly in ulcerative colitis, might influence susceptibility to colonic pathogens such as C difficile. For instance, if ulcerative colitis patients with extensive disease were more prone to C difficile infection it could be convincingly argued that the increased mortality and morbidity observed in this group was in fact just a measure of greater disease extent in this population. In this setting increased C difficile infection would simply serve as a surrogate marker to identify patients with greater disease extent, who unsurprisingly are at increased risk of a more complicated hospital admission. In ulcerative colitis it has been well documented that patients with extensive disease are more likely to develop severe disease, fail conventional medical therapy, require rescue medical therapy, surgery and need more protracted hospital stays.1 2
We also have some preliminary data that implies that colonic infection is indeed more common in patients with more extensive ulcerative colitis. We have recently evaluated the incidence of gastrointestinal infections in the 414 patients with ulcerative colitis at our unit. Over a 1 year period we identified 51 exacerbations of ulcerative colitis where stool samples were sent to our microbiology laboratory for microscopy, culture and C difficile toxin assay. A colonic bacterial pathogen was identified in 17.6% of samples. Like other studies the most commonly implicated pathogenic organism was toxin-secreting C difficile, which was identified in more than 50% of cases.3 In our study, colonic infection was significantly associated with greater disease extent (fig 1). Stool samples acquired during exacerbations from patients with extensive or left-sided disease were significantly more likely to be associated with superimposed infection compared to patients with distal disease (p<0.02).
The mechanisms responsible for increased susceptibility of C difficile infection in patients with more extensive disease extent, rather than distal disease are potentially manifold. One possibility is that the larger the area of colon affected by ulcerative colitis, the greater the resultant impairment in mucosal barrier function and immunity to colonic pathogens. Furthermore, patients with more extensive ulcerative colitis have a greater likelihood of progressing to more severe disease with the attendant requirements for corticosteroids, immunomodulators, rescue medical therapies (such as ciclosporine and infliximab), and also the need for prolonged hospital admission, which is particularly relevant as C difficile is commonly acquired nosocomially. For this reason we would also suggest that prolonged hospital stay is in fact a risk factor for, rather than a consequence of, C difficile infection, as argued by Ananthakrishnan et al.
We would contend that without matching or controlling for disease extent it is difficult to attribute the excess risk of morbidity and mortality to concomitant C difficile infection in hospitalised patients with IBD, especially if greater inflammatory bowel disease extent proves to be a risk factor for colonic infection.
Competing interests: None.
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